Karen L Koenig, Ph.D.

Endogenous hormones and coronary heart disease in postmenopausal women
Chen, Yu; Zeleniuch-Jacquotte, Anne; Arslan, Alan A; Wojcik, Oktawia; Toniolo, Paolo; Shore, Roy E; Levitz, Mortimer; Koenig, Karen L
2011 Jun;216(2):414-419, Atherosclerosis
The association between serum levels of endogenous estrogens in postmenopausal women and the subsequent risk of coronary heart disease (CHD) was examined in a prospective case-control study nested within the New York University Women's Health Study (NYUWHS). The NYUWHS is a prospective cohort study of 14,274 healthy women enrolled between 1985 and 1991. A total of 99 women who were postmenopausal and free of cardiovascular disease at enrollment and who subsequently experienced CHD, defined as non-fatal myocardial infarction (MI), fatal CHD, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG), were matched 1:2 by baseline age, blood sampling date, and postmenopausal status to controls who remained free of CHD as of the date of diagnosis of the matching case. Biochemical analyses for total estradiol, estrone, percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), and SHBG were performed on pre-diagnostic stored serum samples. Participants had not used any hormone medications in the 6 months prior to blood collection. In the model adjusting only for matching factors, the risk of CHD in the top tertile of calculated bioavailable estradiol was elevated compared with the bottom tertile (OR=2.10; 95% CI=1.13-3.90, P for trend=0.03), and the risk in the top tertile of SHBG was reduced (OR=0.50, 95% CI=0.28-0.92, P for trend<0.01). However, these associations disappeared after adjusting for baseline hypertension status, body mass index, and serum cholesterol levels. These findings suggest that circulating estradiol and SHBG are not associated with CHD risk in postmenopausal women beyond what can be explained by the variation in hypertension status, BMI, and cholesterol
— id: 134306, year: 2011, vol: 216, page: 414, stat: Journal Article,

Circulating Inflammation Markers and Risk of Epithelial Ovarian Cancer
Clendenen TV; Lundin E; Zeleniuch-Jacquotte A; Koenig KL; Berrino F; Lukanova A; Lokshin AE; Idahl A; Ohlson N; Hallmans G; Krogh V; Sieri SA; Muti P; Marrangoni AM; Nolen B; Liu M; Shore RE; Arslan AA
2011 May;20(5):799-810, Cancer epidemiology biomarkers & prevention
BACKGROUND: Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer.METHODS: We conducted a case-control study of 230 cases and 432 individually-matched controls nested within three prospective cohorts to evaluate the association of pre-diagnostic circulating levels of inflammation-related biomarkers (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFalpha, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer. RESULTS: We observed a trend across quartiles for IL-2 (OR(Q4 vs. Q1): 1.57, 95% CI: 0.98, 2.52, p= 0.07), IL-4 (OR(Q4 vs. Q1): 1.50, 95% CI: 0.95, 2.38, p= 0.06), IL-6 (OR(Q4 vs. Q1): 1.63, 95% CI: 1.03, 2.58, p= 0.03), IL-12p40 (OR(Q4 vs. Q1): 1.60, 95% CI: 1.02, 2.51, p= 0.06), and IL-13 (OR(Q4 vs. Q1): 1.42, 95% CI: 0.90, 2.26, p= 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (p-trend=0.01), IL-6 (p-trend=0.01), IL-12p40 (p-trend=0.01), and IL-13 (p-trend=0.04). Odds ratios were not materially different after excluding cases diagnosed less than five years after blood donation or when limited to serous tumors.Conclusions and Impact: This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development this disease
— id: 131785, year: 2011, vol: 20, page: 799, stat: Journal Article,

Factors associated with inflammation markers, a cross-sectional analysis
Clendenen, Tess V; Koenig, Karen L; Arslan, Alan A; Lukanova, Annekatrin; Berrino, Franco; Gu, Yian; Hallmans, Goran; Idahl, Annika; Krogh, Vittorio; Lokshin, Anna E; Lundin, Eva; Muti, Paola; Marrangoni, Adele; Nolen, Brian M; Ohlson, Nina; Shore, Roy E; Sieri, Sabina; Zeleniuch-Jacquotte, Anne
2011 Dec;56(3):769-778, Cytokine
Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFalpha), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal vs. premenopausal women (TNFalpha, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1beta, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women
— id: 141702, year: 2011, vol: 56, page: 769, stat: Journal Article,

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies
Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D
2011 Aug 23;105(5):709-722, British journal of cancer
BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk
— id: 137962, year: 2011, vol: 105, page: 709, stat: Journal Article,

Postmenopausal circulating levels of 2- and 16alpha-hydroxyestrone and risk of endometrial cancer
Zeleniuch-Jacquotte, A; Shore, R E; Afanasyeva, Y; Lukanova, A; Sieri, S; Koenig, K L; Idahl, A; Krogh, V; Liu, M; Ohlson, N; Muti, P; Arslan, A A; Lenner, P; Berrino, F; Hallmans, G; Toniolo, P; Lundin, E
2011 Oct 25;105(9):1458-1464, British journal of cancer
Background:It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16alpha-hydroxy pathway is harmful.Methods:We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16alpha-hydroxyestrone (2-OHE1 : 16alpha-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16alpha-OHE1 were measured using a monoclonal antibody-based enzyme assay.Results:Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16alpha-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16alpha-OHE1 ratio.Conclusion:Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16alpha-OH pathway, protects against endometrial cancer
— id: 139737, year: 2011, vol: 105, page: 1458, stat: Journal Article,

Temporal reliability of cytokines and growth factors in EDTA plasma
Clendenen, Tess V; Arslan, Alan A; Lokshin, Anna E; Idahl, Annika; Hallmans, Goran; Koenig, Karen L; Marrangoni, Adele M; Nolen, Brian M; Ohlson, Nina; Zeleniuch-Jacquotte, Anne; Lundin, Eva
2010 ;3:302-302, BMC research notes
ABSTRACT: BACKGROUND: Cytokines are involved in the development of chronic diseases, including cancer. It is important to evaluate the temporal reproducibility of cytokines in plasma prior to conducting epidemiologic studies utilizing these markers. FINDINGS: We assessed the temporal reliability of CRP, 22 cytokines and their soluble receptors (IL-1alpha, IL-1beta, IL-1RA, IL-2, sIL-2R, IL-4, IL-5, IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, TNFalpha, sTNF-R1, sTNF-R2, IFNalpha, IFNgamma) and eight growth factors (GM-CSF, EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2) in repeated EDTA plasma samples collected an average of two years apart from 18 healthy women (age range: 42-62) enrolled in a prospective cohort study. We also estimated the correlation between serum and plasma biomarker levels using 18 paired clinical samples from postmenopausal women (age range: 75-86).Twenty-six assays were able to detect their analytes in at least 70% of samples. Of those 26 assays, we observed moderate to high intra-class correlation coefficients (ICCs)(ranging from 0.53-0.89) for 22 assays, and low ICCs (0-0.47) for four assays. Serum and plasma levels were highly correlated (r > 0.6) for most markers, except for seven assays (r < 0.5). CONCLUSIONS: For 22 of the 31 biomarkers, a single plasma measurement is a reliable estimate of a woman's average level over a two-year period
— id: 115276, year: 2010, vol: 3, page: 302, stat: Journal Article,

Body-Mass Index and Mortality among 1.46 Million White Adults
de Gonzalez, Amy Berrington; Hartge, Patricia; Cerhan, James R.; Flint, Alan J.; Hannan, Lindsay; MacInnis, Robert J.; Moore, Steven C.; Tobias, Geoffrey S.; Anton-Culver, Hoda; Freeman, Laura Beane; Beeson, W. Lawrence; Clipp, Sandra L.; English, Dallas R.; Folsom, Aaron R.; Freedman, D. Michal; Giles, Graham; Hakansson, Niclas; Henderson, Katherine D.; Hoffman-Bolton, Judith; Hoppin, Jane A.; Koenig, Karen L.; Lee, I-Min; Linet, Martha S.; Park, Yikyung; Pocobelli, Gaia; Schatzkin, Arthur; Sesso, Howard D.; Weiderpass, Elisabete; Willcox, Bradley J.; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Willett, Walter C.; Thun, Michael J.
2010 DEC 2 ;363(23):2211-2219, New England journal of medicine
Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9. N Engl J Med 2010;363:2211-9
— id: 115284, year: 2010, vol: 363, page: 2211, stat: Journal Article,

Circulating 25-hydroxyvitamin D and the risk of rarer cancers: Design and methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Gallicchio, Lisa; Helzlsouer, Kathy J; Chow, Wong-Ho; Freedman, D Michal; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Koenig, Karen L; Kolonel, Laurence N; Laden, Francine; McCullough, Marjorie L; Parisi, Dominick; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Stolzenberg-Solomon, Rachael Z; Tworoger, Shelley S; Varanasi, Arti; Virtamo, Jarmo; Wilkens, Lynne R; Xiang, Yong-Bing; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Abnet, Christian C; Albanes, Demetrius; Bertrand, Kimberly; Weinstein, Stephanie J
2010 Jul 1;172(1):10-20, American journal of epidemiology
The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974-2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50-<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations
— id: 134375, year: 2010, vol: 172, page: 10, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of kidney cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Gallicchio, Lisa; Moore, Lee E; Stevens, Victoria L; Ahn, Jiyoung; Albanes, Demetrius; Hartmuller, Virginia; Setiawan, V Wendy; Helzlsouer, Kathy J; Yang, Gong; Xiang, Yong-Bing; Shu, Xiao-Ou; Snyder, Kirk; Weinstein, Stephanie J; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Cai, Qiuyin; Campbell, David S; Chen, Yu; Chow, Wong-Ho; Horst, Ronald L; Kolonel, Laurence N; McCullough, Marjorie L; Purdue, Mark P; Koenig, Karen L
2010 Jul 1;172(1):47-57, American journal of epidemiology
Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of > or =75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically
— id: 132233, year: 2010, vol: 172, page: 47, stat: Journal Article,

Circulating cytokines and risk of B-cell non-Hodgkin lymphoma: a prospective study
Gu, Yian; Shore, Roy E; Arslan, Alan A; Koenig, Karen L; Liu, Mengling; Ibrahim, Sherif; Lokshin, Anna E; Zeleniuch-Jacquotte, Anne
2010 Aug;21(8):1323-1333, Cancer causes & control. ccc
Cytokines play important roles in B-cell activation, proliferation, and apoptosis, thus may be etiologically related to risk of B-cell non-Hodgkin lymphoma (B-NHL). However, the association between circulating levels of cytokines and B-NHL risk has not been prospectively studied in non-HIV populations. The objective of this study was to assess this association by conducting a case-control study nested within a prospective cohort of non-HIV-infected, healthy women. Fifteen cytokines were measured in samples collected a median of 8.2 years prior to diagnosis in 92 cases and two matched controls per case. Only cytokines that showed adequate temporal reproducibility over a two-year period were included. The odds ratio (OR) for the highest tertile relative to the lowest was elevated for soluble IL-2 receptor (sIL-2R) (OR = 2.5, 95% CI = 1.4-4.7, p (trend) < 0.01) and decreased for IL-13 (OR = 0.5, 95% CI = 0.2-1.0, p (trend) = 0.05). Three other cytokines were marginally associated with risk of B-NHL: TNF-alpha (OR = 1.7, 95% CI = 0.9-3.3, p (trend) = 0.11), sTNF-R2 (OR = 1.9, 95% CI = 0.9-3.5, p (trend) = 0.06), and IL-5 (OR = 0.5, 95% CI = 0.3-1.0, p (trend) = 0.06). No association was observed between B-NHL risk and levels of the other cytokines measured (IL-1beta, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, IL-12p70, CRP and sTNF-R1). This study suggests that dysregulated cytokines may be involved in B-NHL development
— id: 138134, year: 2010, vol: 21, page: 1323, stat: Journal Article,

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
McCullough, Marjorie L; Weinstein, Stephanie J; Freedman, D Michal; Helzlsouer, Kathy; Flanders, W Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Shu, Xiao-Ou
2010 Jul 1;172(1):21-35, American journal of epidemiology
Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes
— id: 132232, year: 2010, vol: 172, page: 21, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N
2010 Jul 1;172(1):81-93, American journal of epidemiology
Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered
— id: 134377, year: 2010, vol: 172, page: 81, stat: Journal Article,

Temporal reproducibility of taurine measurements in frozen serum of healthy postmenopausal women
Wojcik, Oktawia P; Koenig, Karen L; Zeleniuch-Jacquotte, Anne; Costa, Max; Chen, Yu
2010 Sep;104(5):629-632, British journal of nutrition
Animal studies and small clinical trials have shown that taurine (2-aminoethanesulphonic acid), a sulphur-containing molecule mainly obtained from the diet in human subjects, has a variety of biological actions that are related to atherosclerosis and cardiovascular functions. However, epidemiological studies of taurine and CHD risk are lacking. We evaluated whether a single measurement of serum taurine could serve as an estimate for long-term serum levels. Serum taurine was measured using HPLC in three annual samples from thirty postmenopausal women selected from the New York University Women's Health Study. Overall, serum taurine values ranged from 62.8 to 245.3 nmol/ml, with a mean of 140 nmol/ml. The intraclass correlation coefficient of a single measurement of serum taurine was 0.48 (95 % CI 0.26, 0.68), which can be improved to 0.65 by using the mean of two annual measurements. The CV was 7 %. These results indicate that the mean of two or more annual measurements of serum taurine is a sufficiently reliable measure of long-term serum levels that can be used in epidemiological studies
— id: 132231, year: 2010, vol: 104, page: 629, stat: Journal Article,

The potential protective effects of taurine on coronary heart disease
Wojcik, Oktawia P; Koenig, Karen L; Zeleniuch-Jacquotte, Anne; Costa, Max; Chen, Yu
2010 Jan;208(1):19-25, Atherosclerosis
In humans, taurine (2-aminoethanesulfonic acid) is mainly obtained from diet. Despite the fact that the health effects of taurine are largely unknown, taurine has become a popular supplement and ingredient in energy drinks in recent years. Evidence from mechanistic and animal studies has shown that the main biological actions of taurine include its ability to conjugate bile acids, regulate blood pressure (BP), and act as a potent antioxidant and anti-inflammatory agent. These actions suggest that high levels of taurine may be protective against coronary heart disease (CHD). However, data from epidemiologic and intervention studies in humans are limited. We review what is known about taurine\'s metabolism, its transportation in the body, its food sources, and evidence of its effect on cardiovascular health from in vitro, animal, and epidemiologic studies. We also discuss shortcomings of the human studies that need to be addressed in the future. The identification of taurine as a preventive factor for CHD may be of great public health importance
— id: 101575, year: 2010, vol: 208, page: 19, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Zeleniuch-Jacquotte, Anne; Gallicchio, Lisa; Hartmuller, Virginia; Helzlsouer, Kathy J; McCullough, Marjorie L; Setiawan, V Wendy; Shu, Xiao-Ou; Weinstein, Stephanie J; Weiss, Jocelyn M; Arslan, Alan A; De Vivo, Immaculata; Gao, Yu-Tang; Hayes, Richard B; Henderson, Brian E; Horst, Ronald L; Koenig, Karen L; Patel, Alpa V; Purdue, Mark P; Snyder, Kirk; Steplowski, Emily; Yu, Kai; Zheng, Wei; Hankinson, Susan E
2010 Jul 1;172(1):36-46, American journal of epidemiology
A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50-<75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the <25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the > or =100 nmol/L category (P(trend) = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was > or =100 nmol/L, and for stratified analyses, > or =75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer
— id: 110661, year: 2010, vol: 172, page: 36, stat: Journal Article,

Circulating vitamin d and risk of epithelial ovarian cancer
Arslan, Alan A; Clendenen, Tess V; Koenig, Karen L; Hultdin, Johan; Enquist, Kerstin; Agren, Asa; Lukanova, Annekatrin; Sjodin, Hubert; Zeleniuch-Jacquotte, Anne; Shore, Roy E; Hallmans, Goran; Toniolo, Paolo; Lundin, Eva
2009 ;2009:672492-672492, Journal of oncology
We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59-2.01). In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist
— id: 101966, year: 2009, vol: 2009, page: 672492, stat: Journal Article,

Circulating estrogen metabolites and risk for breast cancer in premenopausal women
Arslan, Alan A; Shore, Roy E; Afanasyeva, Yelena; Koenig, Karen L; Toniolo, Paolo; Zeleniuch-Jacquotte, Anne
2009 Aug;18(8):2273-2279, Cancer epidemiology biomarkers & prevention
BACKGROUND: It has been proposed that a shift toward 2-hydroxyestrone from 16alpha-hydroxyestrone metabolic pathway may be inversely associated with breast cancer risk because 2-hydroxyestrone is thought to be less genotoxic and estrogenic than 16alpha-hydroxyestrone. METHODS: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2-hydroxyestrone:16alpha-hydroxyestrone ratio in a case-control study on premenopausal women nested within a prospective cohort the New York University Women's Health Study. The serum levels of 2-hydroxyestrone and 16alpha-hydroxyestrone were measured in 377 incident premenopausal breast cancer cases and 377 premenopausal controls, who were matched on age at enrollment, number and dates of blood donations, and day and phase of menstrual cycle. RESULTS: Overall, no significant associations were observed between breast cancer risk and serum levels of 2-hydroxyestrone, 16alpha-hydroxyestrone, or their ratio. The 2-hydroxyestrone:16alpha-hydroxyestrone ratio was positively associated with risk for estrogen receptor-positive breast cancer in the analyses controlling for matching factors. However, the association was attenuated and not significant after adjustment for potential confounders (odds ratio for the highest versus the lowest quartile, 2.15; 95% CI, 0.88-5.27; P(trend) = 0.09). CONCLUSIONS: The results of the current study do not support the hypothesis that a metabolic shift from 16alpha-hydroxyestrone toward 2-hydroxyestrone in premenopausal women is associated with reduced risk for breast cancer. The association between the 2-hydroxy:16alpha-hydroxyestrone ratio and estrogen receptor-positive breast cancer needs to be explored in future studies
— id: 101449, year: 2009, vol: 18, page: 2273, stat: Journal Article,

Job Strain in Physical Therapists
Campo, Marc A; Weiser, Sherri; Koenig, Karen L
2009 Sep;89(9):946-956, Physical therapy
Background Job stress has been associated with poor outcomes. In focus groups and small-sample surveys, physical therapists have reported high levels of job stress. Studies of job stress in physical therapy with larger samples are needed. Objective The purposes of this study were: (1) to determine the levels of psychological job demands and job control reported by physical therapists in a national sample, (2) to compare those levels with national norms, and (3) to determine whether high demands, low control, or a combination of both (job strain) increases the risk for turnover or work-related pain. Design This was a prospective cohort study with a 1-year follow-up period. METHODS:/b> Participants were randomly selected members of the American Physical Therapy Association (n=882). Exposure assessments included the Job Content Questionnaire (JCQ), a commonly used instrument for evaluation of the psychosocial work environment. OUTCOMES: included job turnover and work-related musculoskeletal disorders. RESULTS: /b> Compared with national averages, the physical therapists reported moderate job demands and high levels of job control. About 16% of the therapists reported changing jobs during follow-up. Risk factors for turnover included high job demands, low job control, job strain, female sex, and younger age. More than one half of the therapists reported work-related pain. Risk factors for work-related pain included low job control and job strain. Limitations The JCQ measures only limited dimensions of the psychosocial work environment. All data were self-reported and subject to associated bias. CONCLUSIONS:/b> Physical therapists' views of their work environments were positive, including moderate levels of demands and high levels of control. Those therapists with high levels of demands and low levels of control, however, were at increased risk for both turnover and work-related pain. Physical therapists should consider the psychosocial work environment, along with other factors, when choosing a job
— id: 101235, year: 2009, vol: 89, page: 946, stat: Journal Article,

Targeted deletion of the genes encoding NTH1 and NEIL1 DNA N-glycosylases reveals the existence of novel carcinogenic oxidative damage to DNA
Chan, Michael K; Ocampo-Hafalla, Maria T; Vartanian, Vladimir; Jaruga, Pawel; Kirkali, Guldal; Koenig, Karen L; Brown, Stuart; Lloyd, R Stephen; Dizdaroglu, Miral; Teebor, George W
2009 Jul 4;8(7):786-794, DNA repair (Amsterdam)
We have generated a strain of mice lacking two DNA N-glycosylases of base excision repair (BER), NTH1 and NEIL1, homologs of bacterial Nth (endonuclease three) and Nei (endonuclease eight). Although these enzymes remove several oxidized bases from DNA, they do not remove the well-known carcinogenic oxidation product of guanine: 7,8-dihydro-8-oxoguanine (8-OH-Gua), which is removed by another DNA N-glycosylase, OGG1. The Nth1(-/-)Neil1(-/-) mice developed pulmonary and hepatocellular tumors in much higher incidence than either of the single knockouts, Nth1(-/-) and Neil1(-/-). The pulmonary tumors contained, exclusively, activating GGT-->GAT transitions in codon 12 of K-ras of their DNA. Such transitions contrast sharply with the activating GGT-->GTT transversions in codon 12 of K-ras of the pathologically similar pulmonary tumors, which arose in mice lacking OGG1 and a second DNA N-glycosylase, MUTY. To characterize the biochemical phenotype of the knockout mice, the content of oxidative DNA base damage was analyzed from three tissues isolated from control, single and double knockout mice. The content of 8-OH-Gua was indistinguishable among all genotypes. In contrast, the content of 4,6-diamino-5-formamidopyrimidine (FapyAde) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) derived from adenine and guanine, respectively, were increased in some but not all tissues of Neil1(-/-) and Neil1(-/-)Nth1(-/-) mice. The high incidence of tumors in our Nth1(-/-)Neil1(-/-) mice together with the nature of the activating mutation in the K-ras gene of their pulmonary tumors, reveal for the first time, the existence of mutagenic and carcinogenic oxidative damage to DNA which is not 8-OH-Gua
— id: 100475, year: 2009, vol: 8, page: 786, stat: Journal Article,

Postmenopausal levels of endogenous sex hormones and risk of colorectal cancer
Clendenen, Tess V; Koenig, Karen L; Shore, Roy E; Levitz, Mortimer; Arslan, Alan A; Zeleniuch-Jacquotte, Anne
2009 Jan;18(1):275-281, Cancer epidemiology biomarkers & prevention
Observational epidemiologic studies and randomized trials have reported a protective effect of oral hormonal replacement therapy on risk of colorectal cancer. Only one previous prospective study, the Women's Health Initiative Observational Study, has reported on the relationship between endogenous hormones and incident colorectal cancer. Contrary to expectation, the investigators found that women with higher circulating estradiol levels were at increased risk of developing colorectal cancer. We conducted a case-control study nested within the New York University Women's Health Study prospective cohort to evaluate the association between endogenous levels of estrone, estradiol, and sex hormone-binding globulin (SHBG) with risk of colorectal cancer. We measured hormones and SHBG in serum samples collected at enrollment from a total of 148 women who subsequently developed colorectal cancer and 293 matched controls. Circulating estrone levels were positively associated with risk of colorectal cancer: The odds ratio for the highest versus lowest quartile of estrone was 1.8 (95% confidence interval, 1.0-3.3). We found a nonsignificant inverse association between SHBG and colorectal cancer, which disappeared after adjusting for body mass index. We did not find an association between estradiol and colorectal cancer risk, but we cannot rule out a potential association because of substantial laboratory error in the measurement. Our results suggest that endogenous estrone is associated with increased risk of colorectal cancer in postmenopausal women
— id: 92142, year: 2009, vol: 18, page: 275, stat: Journal Article,

Reproducibility of serum cytokines and growth factors
Gu, Yian; Zeleniuch-Jacquotte, Anne; Linkov, Faina; Koenig, Karen L; Liu, Mengling; Velikokhatnaya, Lyudmila; Shore, Roy E; Marrangoni, Adele; Toniolo, Paolo; Lokshin, Anna E; Arslan, Alan A
2009 Jan;45(1):44-49, Cytokine
BACKGROUND: In most studies, circulating biomarkers are usually assessed from a single sample, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested although it may not be valid for all biomarkers. The objective of this study was to investigate the temporal reproducibility of a panel of cytokines and growth factors. METHODS: Thirty-five postmenopausal women with two annual visits and 30 premenopausal women with three annual visits were randomly selected from the participants in an existing prospective cohort. A total of 23 serum cytokines, nine growth factors and C-reactive protein (CRP) were measured using the Luminex xMap technology. In addition, for eight biomarkers, regular and high sensitivity (hs) assays were compared. RESULTS: The biomarkers with adequate (>60%) detection rates and acceptable (> or =0.55) intra-class correlation coefficients (ICCs) were: hsIL-1beta, IL-1RA, hsIL-2, hsIL-4, hsIL-5, hsIL-6, hsIL-10, IL-12p40, hsIL-12p70, hsTNF-alpha, TNF-R1, TNF-R2, CRP, HGF, NGF, and EGFR. The remaining biomarkers either had low temporal reproducibility or were undetectable in more than 40% of samples. CONCLUSIONS: The results suggest that 16 of the 41 biomarkers measured with Luminex technology showed sufficient sensitivity and temporal reproducibility in sera
— id: 92177, year: 2009, vol: 45, page: 44, stat: Journal Article,

Reliability of tumor markers, chemokines, and metastasis-related molecules in serum
Linkov, Faina; Gu, Yian; Arslan, Alan A; Liu, Mengling; Shore, Roy E; Velikokhatnaya, Lyudmila; Koenig, Karen L; Toniolo, Paolo; Marrangoni, Adele; Yurkovetsky, Zoya; Zeleniuch-Jacquotte, Anne; Lokshin, Anna E
2009 Mar;20(1):21-26, European cytokine network
There is a growing interest in the role that cancer biomarkers, metastasis-related molecules, and chemokines may play in the development and progression of various cancers. However, few studies have addressed the reliability of such biomarkers in healthy individuals over time. The objective of this study was to investigate the temporal reliability of multiple proteins in serum samples from healthy women who donated blood over successive years. Thirty five, postmenopausal women with two, repeated annual visits, and thirty, premenopausal women with three, repeated annual visits were randomly selected among eligible subjects from an existing, prospective cohort. Multiplexing Luminex xMAPTM technology was used to measure the levels of 55 serum proteins representing cancer antigens, chemokines, angiogenic and anti-angiogenic factors, proteases, adipokines, apoptotic molecules, and other markers in these women. The biomarkers with high detection rates (> 60%) and acceptable reliability (intraclass correlation coefficient, ICCs > or = 0.55) using xMAPTM method were: cancer antigens: AFP, CA 15-3, CEA, CA-125, SCC, SAA; growth factors/related molecules: ErbB2, IGFBP-1; proteases and adhesion molecules: MMP-1, 8, 9, sE-selectin, human kallikreins (KLK) 8,10, ICAM-1, VCAM-1, chemokines: fractalkine, MCP-1,2, RANTES, MIP-1alpha, MIP-1beta, Eotaxin, GRO-alpha, IP-10; inhibitors of angiogenesis: angiostatin and endostatin; adipokines leptin and resistin; apoptotic factor: Fas, and other proteins mesothelin, myeloperoxidase (MPO), and PAI-1. The rest of the biomarkers under investigation either had ICCs less than 0.55 or had low levels of detection (< 60%). These included cancer antigens: CA 19-9, CA 72-4, MICA, S100, TTR, ULBP1, ULBP2, ULBP3; proteases: MMP 2, 3, 7, 12, 13; chemokines: MCP-3, MIF, MIG; adipokines: leptin and resistin; apoptotic factors: FasL, DR5, Cyfra 21-1; and inhibitors of angiogenesis and other markers: thrombospondin and heat shock protein (HSP) 27. In conclusion, 34 out of the 55 biomarkers investigated were present in detectable levels in > 60% of the samples, and with an ICC > or = 0.55, indicating that a single serum measurement can be used in prospective epidemiological studies using the xMAPTM method
— id: 126591, year: 2009, vol: 20, page: 21, stat: Journal Article,

Reproducibility of serum pituitary hormones in women
Arslan, Alan A; Gu, Yian; Zeleniuch-Jacquotte, Anne; Koenig, Karen L; Liu, Mengling; Velikokhatnaya, Lyudmila; Shore, Roy E; Toniolo, Paolo; Linkov, Faina; Lokshin, Anna E
2008 Aug;17(8):1880-1883, Cancer epidemiology biomarkers & prevention
Endogenous pituitary hormones are commonly used in clinical and epidemiologic studies and some of them are thought to influence the risk of several diseases in women. In most studies, endogenous levels of pituitary hormones are usually assessed at a single point in time, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested and may not always be valid. This study examined the reproducibility of the following pituitary hormones: adrenocorticotropic hormone (ACTH), growth hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and prolactin, measured using the Luminex xMap method in sera of healthy premenopausal and postmenopausal women. The study included 30 premenopausal women with three yearly samples and 35 postmenopausal women with two repeated yearly samples randomly selected from an existing prospective cohort. Analysis of intraclass correlation coefficients suggested higher reproducibility in postmenopausal women compared with premenopausal women for the following hormones: FSH (0.72 and 0.37, respectively), LH (0.83 and 0.44, respectively), and growth hormone (0.60 and 0.35, respectively). The intraclass correlation coefficients were relatively high and similar between postmenopausal and premenopausal women for ACTH (0.95 and 0.94, respectively), TSH (0.85 and 0.85, respectively), and prolactin (0.72 and 0.69, respectively). This study found that serum concentrations of FSH, LH, and growth hormone are stable in postmenopausal women and that ACTH, TSH, and prolactin are stable in both premenopausal and postmenopausal women, suggesting that a single measurement may reliably categorize average levels over at least a 2-year period
— id: 91436, year: 2008, vol: 17, page: 1880, stat: Journal Article,

Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk
Brooks, Jennifer; Shore, Roy E; Zeleniuch-Jacquotte, Anne; Currie, Diane; Afanasyeva, Yelena; Koenig, Karen L; Arslan, Alan A; Toniolo, Paolo; Wirgin, Isaac
2008 Apr;17(4):1016-1019, Cancer epidemiology biomarkers & prevention
— id: 80287, year: 2008, vol: 17, page: 1016, stat: Journal Article,

Work-related musculoskeletal disorders in physical therapists: a prospective cohort study with 1-year follow-up
Campo, Marc; Weiser, Sherri; Koenig, Karen L; Nordin, Margareta
2008 May;88(5):608-619, Physical therapy
BACKGROUND: Work-related musculoskeletal disorders (WMSDs) have a significant impact on physical therapists, but few studies have addressed the issue. Research is needed to determine the scope of the problem and the effects of specific risk factors. OBJECTIVES: The objectives of this study were: (1) to determine the 1-year incidence rate of WMSDs in physical therapists and (2) to determine the effects of specific risk factors. DESIGN: This was a prospective cohort study with 1-year follow-up. METHODS: Subjects were randomly selected American Physical Therapy Association members (N=882). Exposure assessment included demographic data, physical risk factors, job strain, and specific physical therapy tasks. The primary outcome was WMSDs, with a severity rating of at least 4/10 and present at least once a month or lasting longer than a week. RESULTS: The response rate to the baseline questionnaire was 67%. Ninety-three percent of the subjects who responded to the baseline questionnaire responded to the follow-up questionnaire. The 1-year incidence rate of WMSDs was 20.7%. Factors that increased the risk for WMSDs included patient transfers, patient repositioning, bent or twisted postures, joint mobilization, soft tissue work, and job strain. LIMITATIONS: The primary limitation of this study was the number of therapists who had a change in their job situation during the follow-up year. CONCLUSIONS: Work-related musculoskeletal disorders are prevalent in physical therapists. Physical therapy exposures, patient handling, and manual therapy, in particular, increase the risk for WMSDs
— id: 78454, year: 2008, vol: 88, page: 608, stat: Journal Article,

Vitamin D receptor polymorphisms and risk of epithelial ovarian cancer
Clendenen, Tess V; Arslan, Alan A; Koenig, Karen L; Enquist, Kerstin; Wirgin, Isaac; Agren, Asa; Lukanova, Annekatrin; Sjodin, Hubert; Zeleniuch-Jacquotte, Anne; Shore, Roy E; Hallmans, Goran; Toniolo, Paolo; Lundin, Eva
2008 Feb 18;260(1-2):209-215, Cancer letters
The vitamin D receptor (VDR) is a critical mediator of the cellular effects of vitamin D. The associations between four common VDR polymorphisms (BSMI, APAI, TAQI, and FOKI) and risk of epithelial ovarian cancer (EOC) were assessed in a case-control study nested within two prospective cohorts. One hundred seventy incident cases of EOC and 323 individually matched controls were genotyped. Overall, no associations were observed in genotype analyses. Haplotypes combining three SNPs in high linkage disequilibrium (BSMI, APAI, and TAQI) were also not associated with risk. These observations do not support a role for BSMI, APAI, TAQI, and FOKI polymorphisms in epithelial ovarian cancer in a predominantly Caucasian population
— id: 76858, year: 2008, vol: 260, page: 209, stat: Journal Article,

CrVI exposure and biomarkers: Cr in erythrocytes in relation to exposure and polymorphisms of genes encoding anion transport proteins
Qu, Qingshan; Li, Xiaomei; An, Feiyun; Jia, Guang; Liu, Lanzeng; Watanabe-Meserve, Hiroko; Koenig, Karen; Cohen, Beverly; Costa, Max; Roy, Nirmal; Zhong, Mianhua; Chen, Lung Chi; Liu, Suhua; Yan, Lei
2008 Aug;13(5):467-477, Biomarkers
A total of 195 subjects, including 141 exposed workers and 54 farmers, were recruited in China to evaluate the usefulness of chromium (Cr) in erythrocytes as a biomarker of exposure to CrVI. The levels of Cr in red blood cells (RBC) were remarkably elevated even in a group of workers routinely exposed to CrVI as low as 5-15 microg m(-3) and showed a significant exposure-response trend over the exposure range from 0.002 to 1152 microg m(-3) (p <0.0001). Multiple linear regression analyses indicated that age and cigarette smoke were not associated with Cr in RBC. However, female subjects had lower Cr in RBC compared with their male counterparts for about the same exposure levels (p <0.05). The genotypes of band III, which encodes for anion transport protein and may regulate CrO4(-2) across cell membranes, were also identified and included for analysis. The ratios of Cr in RBC to CrVI exposure were higher in subjects with a wild genotype than in those who had heterozygous or homozygous variant alleles. However, the difference was not statistically significant probably due to the limited number of participating subjects. In addition, 15 of the 141 workers were selected for multiple exposure monitoring and blood sample collections to evaluate the inter- and intraindividual variations of Cr in RBC. Compared with the personal exposure levels, Cr in RBC had small intraindividual variations with a reliability coefficient of 0.88. The study suggests that Cr in RBC may serve as a sensitive and reliable biomarker for long-term exposure to CrVI
— id: 93384, year: 2008, vol: 13, page: 467, stat: Journal Article,

Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk
Shore, Roy E; Zeleniuch-Jacquotte, Anne; Currie, Diane; Mohrenweiser, Harvey; Afanasyeva, Yelena; Koenig, Karen L; Arslan, Alan A; Toniolo, Paolo; Wirgin, Isaac
2008 May 1;122(9):2101-2105, International journal of cancer
To evaluate the associations of breast cancer risk with polymorphisms in the XPC and XPD/ERCC2 DNA nucleotide excision repair genes, a case-control study nested within a prospective cohort of 14,274 women was conducted. Genotypes were characterized for 612 incident, invasive breast cancer cases and their 1:1 matched controls. The homozygous variant of a poly(AT) insertion/deletion polymorphism in intron 9 of the XPC gene (XPC-PAT+/+), was associated with breast cancer risk [odds ratio (OR) = 1.45, 95% confidence interval: 1.07-1.97], after adjustment for other breast cancer risk factors. The breast cancer risk associated with XPC-PAT+/+ did not differ by age at diagnosis. There was an indication of an interaction (p = 0.08) between the XPC-PAT+/+ genotype and cigarette smoking. Ever smokers with the XPC-PAT+/+ genotype were at elevated risk of breast cancer (OR = 1.56, CI: 0.95-2.58), but no differences were observed among never smokers. Analyses of the ERCC2 Lys751Gln polymorphism did not show an association with breast cancer risk, either overall or at younger ages. The results suggest that breast cancer risk is related to the XPC haplotype tagged by the XPC-PAT+/+ insertion-deletion polymorphism in intron 9. Further study of the XPC haplotypes and their interactions with smoking in relation to breast cancer risk is needed
— id: 76390, year: 2008, vol: 122, page: 2101, stat: Journal Article,

Re: C-reactive protein and risk of breast cancer
Zeleniuch-Jacquotte, Anne; Gu, Yian; Bruning, Peter F; Bonfrer, Johannes M G; Koenig, Karen L; Arslan, Alan A; Toniolo, Paolo; Shore, Roy E
2008 Mar 19;100(6):443-444, Journal of the National Cancer Institute
— id: 93619, year: 2008, vol: 100, page: 443, stat: Journal Article,

Reliability of serum assays of iron status in postmenopausal women
Zeleniuch-Jacquotte, Anne; Zhang, Qi; Dai, Jisen; Shore, Roy E; Arslan, Alan A; Koenig, Karen L; Karkoszka, Jerzy; Afanasyeva, Yelena; Frenkel, Krystyna; Toniolo, Paolo; Huang, Xi
2007 May;17(5):354-358, Annals of epidemiology
PURPOSE: The aim of the study is to determine the reliability during a 2-year period of several newly developed iron-related assays to assess their potential for use in prospective epidemiologic studies. METHODS: We assessed the temporal reliability of several iron-related assays by using three serum samples collected at yearly intervals from 50 postmenopausal participants in a large prospective study. RESULTS: We observed high reliability coefficients for ferritin (0.78; 95% confidence interval [CI], 0.67-0.86), soluble transferrin receptor (sTfR; 0.79; 95% CI, 0.69-0.87), sTfR/ferritin ratio (0.74; 95% CI, 0.62-0.83), and hepcidin (0.89; 95% CI, 0.84-0.94). In a subset of 30 women, lower reliability was observed for serum iron (0.50; 95% CI, 0.29-0.70), unsaturated iron-binding capacity (0.55; 95% CI, 0.34-0.73), total iron-binding capacity (0.60; 95% CI, 0.40-0.76), and serum transferrin saturation rate (0.44; 95% CI, 0.22-0.65). The reliability of anti-5-hydroxymethyl-2'-deoxyuridine autoantibody titers, a biomarker of oxidized DNA damage, one of the mechanisms by which iron is thought to impact disease risk, was very high (0.97, 95% CI, 0.5-0.99). CONCLUSIONS: Our results show that some newly developed iron-related assays could be useful tools to assess iron-disease associations in prospective cohorts that collect a single blood sample
— id: 73252, year: 2007, vol: 17, page: 354, stat: Journal Article,

A pooled analysis of 12 cohort studies of dietary fat, cholesterol and egg intake and ovarian cancer
Genkinger, Jeanine M; Hunter, David J; Spiegelman, Donna; Anderson, Kristin E; Beeson, W Lawrence; Buring, Julie E; Colditz, Graham A; Fraser, Gary E; Freudenheim, Jo L; Goldbohm, R Alexandra; Hankinson, Susan E; Koenig, Karen L; Larsson, Susanna C; Leitzmann, Michael; McCullough, Marjorie L; Miller, Anthony B; Rodriguez, Carmen; Rohan, Thomas E; Ross, Julie A; Schatzkin, Arthur; Schouten, Leo J; Smit, Ellen; Willett, Walter C; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zhang, Shumin M; Smith-Warner, Stephanie A
2006 Apr;17(3):273-285, Cancer causes & control. ccc
Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case-control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86-1.34 comparing > or =45 to 30-<35% of calories). No association was observed for monounsaturated, polyunsaturated, trans-unsaturated, animal and vegetable fat, cholesterol and egg intakes with ovarian cancer risk. A weakly positive, but non-linear association, was observed for saturated fat intake (pooled multivariate RR = 1.29, 95% CI: 1.01-1.66 comparing highest versus lowest decile). Results for histologic subtypes were similar. Overall, fat, cholesterol and egg intakes were not associated with ovarian cancer risk. The positive association for saturated fat intake at very high intakes merits further investigation
— id: 72086, year: 2006, vol: 17, page: 273, stat: Journal Article,

Circulating enterolactone and risk of endometrial cancer
Zeleniuch-Jacquotte, Anne; Lundin, Eva; Micheli, Andrea; Koenig, Karen L; Lenner, Per; Muti, Paola; Shore, Roy E; Johansson, Ingegerd; Krogh, Vittorio; Lukanova, Annekatrin; Stattin, Par; Afanasyeva, Yelena; Rinaldi, Sabina; Arslan, Alan A; Kaaks, Rudolf; Berrino, Franco; Hallmans, Goran; Toniolo, Paolo; Adlercreutz, Herman
2006 Nov 15;119(10):2376-2381, International journal of cancer
It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer
— id: 69245, year: 2006, vol: 119, page: 2376, stat: Journal Article,

Personal and occupational exposure to organic solvents and risk of non-Hodgkin's lymphoma (NHL) in women (United States)
Kato, Ikuko; Koenig, Karen L; Watanabe-Meserve, Hiroko; Baptiste, Mark S; Lillquist, Patricia P; Frizzera, Glauco; Burke, Jerome S; Moseson, Miriam; Shore, Roy E
2005 Dec;16(10):1215-1224, Cancer causes & control. ccc
OBJECTIVES: The authors assessed whether home and occupational exposure to organic solvents is associated with risk of NHL in women. METHODS: A population-based, incidence case-control study was conducted in upstate New York, involving 376 NHL cases and 463 population controls selected from the Medicare beneficiary files and State driver's license records. Exposure information was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model, adjusting for a number of risk factors for NHL. RESULTS: Overall, history of exposure to organic solvents was not associated with the risk of NHL. A statistically significant increase in risk associated with occupational exposure was observed only for the subjects whose first exposure occurred before 1970 (OR=1.87, 95% CI 1.03-3.40). When occupational and home exposures to paint thinners/turpentine were combined and analyzed together, the risk of NHL associated with any exposure, compared to no exposure at either job or home, was a statistically significantly increased (OR=1.46, 95% CI: 1.05-2.03). This observation was more pronounced for B-cell lymphoma and for low-grade lymphoma with ORs of 1.52 (95 CI: 1.08-2.14) and 2.20 (95% CI; 1.42-3.41), respectively. CONCLUSIONS: The results of this case-control study do support of a major role of organic solvents in the development of NHL among women currently living in the US. However, relatively intensive exposure in past occupations and use of paint thinners/turpentine may deserve further investigation
— id: 72139, year: 2005, vol: 16, page: 1215, stat: Journal Article,

Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies
Koushik, Anita; Hunter, David J; Spiegelman, Donna; Anderson, Kristin E; Arslan, Alan A; Beeson, W Lawrence; van den Brandt, Piet A; Buring, Julie E; Cerhan, James R; Colditz, Graham A; Fraser, Gary E; Freudenheim, Jo L; Genkinger, Jeanine M; Goldbohm, R Alexandra; Hankinson, Susan E; Koenig, Karen L; Larsson, Susanna C; Leitzmann, Michael; McCullough, Marjorie L; Miller, Anthony B; Patel, Alpa; Rohan, Thomas E; Schatzkin, Arthur; Smit, Ellen; Willett, Walter C; Wolk, Alicja; Zhang, Shumin M; Smith-Warner, Stephanie A
2005 Sep;14(9):2160-2167, Cancer epidemiology biomarkers & prevention
Because fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions, increased consumption may reduce the risk of ovarian cancer. Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent. We analyzed and pooled the primary data from 12 prospective studies in North America and Europe. Fruit and vegetable intake was measured at baseline in each study using a validated food-frequency questionnaire. To summarize the association between fruit and vegetable intake and ovarian cancer, study-specific relative risks (RR) were estimated using the Cox proportional hazards model, and then combined using a random-effects model. Among 560,441 women, 2,130 cases of invasive epithelial ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies. Total fruit intake was not associated with ovarian cancer risk-the pooled multivariate RR for the highest versus the lowest quartile of intake was 1.06 [95% confidence interval (95% CI), 0.92-1.21; P value, test for trend = 0.73; P value, test for between-studies heterogeneity = 0.74]. Similarly, results for total vegetable intake indicated no significant association (pooled multivariate RR, 0.90; 95% CI, 0.78-1.04, for the highest versus the lowest quartile; P value, test for trend = 0.06; P value, test for between-studies heterogeneity = 0.31). Intakes of botanically defined fruit and vegetable groups and individual fruits and vegetables were also not associated with ovarian cancer risk. Associations for total fruits and vegetables were similar for different histologic types. These results suggest that fruit and vegetable consumption in adulthood has no important association with the risk of ovarian cancer
— id: 72081, year: 2005, vol: 14, page: 2160, stat: Journal Article,

Insulin-like growth factor-I, IGF binding protein-3, and breast cancer in young women: a comparison of risk estimates using different peptide assays
Rinaldi, Sabina; Kaaks, Rudolf; Zeleniuch-Jacquotte, Anne; Arslan, Alan A; Shore, Roy E; Koenig, Karen L; Dossus, Laure; Riboli, Elio; Stattin, Par; Lukanova, Annekatrin; Toniolo, Paolo
2005 Jan;14(1):48-52, Cancer epidemiology biomarkers & prevention
Circulating insulin-like growth factor-I (IGF-I) and its major binding protein IGF binding protein-3 (IGFBP-3) have been associated with increased risk of premenopausal breast cancer, although risk estimates varied broadly. An extension of a case-control study (138 cases, 259 matched controls) on IGF-I and breast cancer in premenopausal women nested in the New York University Women's Health Study cohort offered the opportunity to address the hypothesis that such variability may have been the result of variations in the ability of different IGFBP-3 assays to specifically measure intact/functional forms of the protein. IGF-I and IGFBP-3 had originally been measured using in-house RIAs. These measurements were repeated using commercially available ELISAs [Diagnostic System Laboratories (DSL), Webster, Texas], and a third ELISA with greater specificity for active forms for IGFBP-3. Pearson's correlations between IGF-I concentrations in the original study and DSL ELISA were very high [r = 0.92; 95% CI, 0.90-0.94]. Correlations with DSL ELISA were much lower for IGFBP-3 (r = 0.58; 0.49-0.66) and even lower still with the assay for functional IGFBP-3 (r = 0.33; 0.20-0.44). IGF-I and IGFBP-3 measurements by the DSL ELISA methods showed statistically significant relationships with risk. The odds ratios (OR) for top versus bottom quartiles were 1.93 (1.00-3.72; P = 0.02) and 2.03 (1.09-3.76; P = 0.02), respectively, in agreement with the original observations. In contrast, measurements of functional IGFBP-3 tended to be unrelated to risk [ORs for the top versus bottom quartile, 0.97 (0.44-2.11)]. The association with IGF-I became substantially weaker and lost statistical significance after adjustment for IGFBP-3 using DSL ELISA, but became considerably stronger when adjusting for the functional IGFBP-3 measurements [OR = 2.43 (1.21-4.90); P = 0.005], or when considering the molar ratio of IGF-I to IGFBP-3 [OR = 2.37 (1.13-5.00); P = 0.02]. These results are consistent with an association of breast cancer risk in young women with elevated IGF-I and IGFBP-3, and show that for IGFBP-3, the strength of such an association could vary substantially depending on the assay used
— id: 72082, year: 2005, vol: 14, page: 48, stat: Journal Article,

IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three prospective studies
Rinaldi, Sabina; Toniolo, Paolo; Muti, Paola; Lundin, Eva; Zeleniuch-Jacquotte, Anne; Arslan, Alan; Micheli, Andrea; Lenner, Per; Dossus, Laure; Krogh, Vittorio; Shore, Roy E; Koenig, Karen L; Riboli, Elio; Stattin, Par; Berrino, Franco; Hallmans, Goran; Lukanova, Annekatrin; Kaaks, Rudolf
2005 Dec;14(6):493-496, European journal of cancer prevention
Prospective cohort studies on breast cancer risk among premenopausal women and insulin-like growth factor I (IGF-I) concentrations have so far included only few cases, and have shown inconsistent relative risk estimates. We pooled 220 cases of breast cancer diagnosed before age 50, and 434 control subjects, from three prospective studies in New York (USA), Umea (Northern Sweden) and Milan (Italy), and we measured IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) with common enzyme-linked immunosorbent assays. Overall, IGF-I and IGFBP-3 measurements obtained by the common method showed a positive but not significant relationship with breast cancer risk (odds ratios (ORs) 0.90 [95% confidence intervals (95% CI) 0.50-1.62], 1.63 [0.89-2.97], 1.46 [0.78-2.73] and 1.41 [0.75-2.63] for quintiles of IGF-I, and ORs 0.98 [0.54-1.75], 1.06 [0.59-1.91], 1.04 [0.58-1.87] and 1.77 [0.97-3.24] for quintiles of IGFBP-3). Our results give only moderate support for an association of blood IGF-I with breast cancer risk in young women
— id: 72088, year: 2005, vol: 14, page: 493, stat: Journal Article,

Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: results of a prospective study
Zeleniuch-Jacquotte, Anne; Gu, Yian; Shore, Roy E; Koenig, Karen L; Arslan, Alan A; Kato, Ikuko; Rinaldi, Sabina; Kaaks, Rudolf; Toniolo, Paolo
2005 Mar 20;114(2):323-327, International journal of cancer
We report on a prospective study to assess the association of postmenopausal serum levels of sex hormones with subsequent risk of breast carcinoma in situ. We conducted a case-control study nested within the cohort of the New York University Women's Health Study, a large prospective study documenting a positive association of circulating levels of estrogens and androgens with invasive breast cancer. The study included 69 cases of incident in situ carcinoma and 134 individually matched controls. No statistically significant trend of increasing risk with increasing level of any of the hormones was observed. Odds ratios (95% CIs) for the highest tertile relative to the lowest were 1.10 (0.51-2.39) for estradiol, 0.95 (0.41-2.19) for estrone, 1.63 (0.69-3.88) for testosterone, 0.99 (0.44-2.24) for androstenedione, 0.99 (0.45-2.20) for dehydroepiandrosterone sulfate and 0.81 (0.38-1.74) for sex hormone-binding globulin. Adjusting for potential confounders did not materially affect the results, nor did limiting the analysis to the 59 cases of ductal carcinoma in situ, the lesion thought to be the direct precursor of most invasive breast cancers. Our results are at variance with the positive associations observed in this same cohort with risk of invasive breast cancer. Possible explanations for our results include lack of power, an effect of sex hormones limited to the progression from in situ to invasive tumors, overrepresentation of indolent tumors or an effect of sex hormones on the induction of only a subset of in situ tumors, those that would develop into invasive tumors
— id: 51094, year: 2005, vol: 114, page: 323, stat: Journal Article,

Pesticide product use and risk of non-hodgkin lymphoma in women
Kato, Ikuko; Watanabe-Meserve, Hiroko; Koenig, Karen L; Baptiste, Mark S; Lillquist, Patricia P; Frizzera, Glauco; Burke, Jerome S; Moseson, Miriam; Shore, Roy E
2004 Sep;112(13):1275-1281, Environmental health perspectives
A population-based, incidence case-control study was conducted among women in upstate New York to determine whether pesticide exposure is associated with an increase in risk of non-Hodgkin lymphoma (NHL) among women. The study involved 376 cases of NHL identified through the State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records. Information about history of farm work, history of other jobs associated with pesticide exposure, use of common household pesticide products, and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. The risk of NHL was doubled (OR = 2.12; 95% CI, 1.21-3.71) among women who worked for at least 10 years at a farm where pesticides were reportedly used. When both farming and other types of jobs associated with pesticide exposure were combined, there was a progressive increase in risk of NHL with increasing duration of such work ((italic)p(/italic) = 0.005). Overall cumulative frequency of use of household pesticide products was positively associated with risk of NHL ((italic)p(/italic) = 0.004), which was most pronounced when they were applied by subjects themselves. When exposure was analyzed by type of products used, a significant association was observed for mothballs. The associations with both occupational and household pesticides were particularly elevated if exposure started in 1950-1969 and for high-grade NHL. Although the results of this case-control study suggest that exposure to pesticide products may be associated with an increased risk of NHL among women, methodologic limitations related to selection and recall bias suggest caution in inferring causation. Key words: case-control study, mothballs, NHL, pesticides
— id: 44747, year: 2004, vol: 112, page: 1275, stat: Journal Article,

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women
Lukanova, A; Lundin, E; Zeleniuch-Jacquotte, A; Muti, P; Mure, A; Rinaldi, S; Dossus, L; Micheli, A; Arslan, A; Lenner, P; Shore, R E; Krogh, V; Koenig, K L; Riboli, E; Berrino, F; Hallmans, G; Stattin, P; Toniolo, P; Kaaks, R
2004 Feb;150(2):161-171, European journal of endocrinology
OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women
— id: 44748, year: 2004, vol: 150, page: 161, stat: Journal Article,

Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women
Lukanova, Annekatrin; Lundin, Eva; Micheli, Andrea; Arslan, Alan; Ferrari, Pietro; Rinaldi, Sabina; Krogh, Vittorio; Lenner, Per; Shore, Roy E; Biessy, Carine; Muti, Paola; Riboli, Elio; Koenig, Karen L; Levitz, Mortimer; Stattin, Par; Berrino, Franco; Hallmans, Goran; Kaaks, Rudolf; Toniolo, Paolo; Zeleniuch-Jacquotte, Anne
2004 Jan 20;108(3):425-432, International journal of cancer
Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis
— id: 44750, year: 2004, vol: 108, page: 425, stat: Journal Article,

Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer
Lukanova, Annekatrin; Zeleniuch-Jacquotte, Anne; Lundin, Eva; Micheli, Andrea; Arslan, Alan A; Rinaldi, Sabina; Muti, Paola; Lenner, Per; Koenig, Karen L; Biessy, Carine; Krogh, Vittorio; Riboli, Elio; Shore, Roy E; Stattin, Par; Berrino, Franco; Hallmans, Goran; Toniolo, Paolo; Kaaks, Rudolf
2004 Jan 10;108(2):262-268, International journal of cancer
Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer
— id: 44751, year: 2004, vol: 108, page: 262, stat: Journal Article,

A comparison of survival rates for treatment of melanoma metastatic to the brain
Stone, Anne; Cooper, Jay; Koenig, Karen L; Golfinos, John G; Oratz, Ruth
2004 ;22(4):492-497, Cancer investigation
INTRODUCTION: A retrospective review of 91 patients with brain metastases from malignant melanoma treated at New York University Medical Center between 1989-1999. Overall survival was the outcome evaluated. METHODS: Charts of 91 patients having malignant melanoma with brain metastases were reviewed. Cases were stratified according to therapy: surgical excision, surgical excision plus whole brain radiation therapy, gamma knife stereotactic radiosurgery, gamma knife stereotactic radiosurgery plus whole brain radiation therapy, and whole brain radiation therapy alone. Patients treated with gamma knife stereotactic radiosurgery plus radiation therapy were combined with patients treated with surgical excision plus radiation therapy and compared to those treated with radiation therapy alone. Prognostic characteristics of the two groups were compared and survival curves were generated using the Kaplan-Meier method. The Cox proportional hazards model was used to control for prognostic factors that differed between the groups. RESULTS: Patients treated with gamma knife stereotactic radiosurgery or surgical excision plus radiation therapy were younger, less likely to present with symptoms, and presented with fewer metastases to the brain than patients treated with radiation therapy alone. A survival benefit of 7.3 months (p = 0.05) was found to be associated with gamma knife radiosurgery or surgical excision plus radiation therapy over radiation therapy alone after controlling for differences in age, number of brain lesions, and presence of symptoms. DISCUSSION: This retrospective study of 91 patients treated for melanoma metastases to the brain attempts to examine the effectiveness of different treatments in prolonging survival. Our results suggest that surgical excision or stereotactic radiosurgery with gamma knife in addition to radiation therapy may be more effective than radiation alone at prolonging survival for patients with a limited number of brain lesions. CONCLUSION: Survival of patients with melanoma metastases to the brain may be prolonged by treatment with gamma knife stereotactic radiosurgery or surgical excision plus whole brain radiation therapy
— id: 47821, year: 2004, vol: 22, page: 492, stat: Journal Article,

Detection of melanomas in patients followed up with total cutaneous examinations, total cutaneous photography, and dermoscopy
Wang, Steven Q; Kopf, Alfred W; Koenig, Karen; Polsky, David; Nudel, Kira; Bart, Robert S
2004 Jan;50(1):15-20, Journal of the American Academy of Dermatology
BACKGROUND: Many factors have been identified as important determinants that increase the risk of malignant melanoma (MM) developing. Patients with classic atypical mole syndrome (CAMS) have multiple such factors and are known to be at high risk for MMs developing. OBJECTIVE: We sought to evaluate the risk for newly diagnosed MMs developing in patients with CAMS and in a heterogeneous group of patients at high risk (ie, those with high-risk non-CAMS [HRNCAMS]) who had 1 or more risk factors: personal history of nonmelanoma skin cancers; family history of melanoma; biopsy specimen-confirmed dysplastic nevi; and meeting 1 or 2 of the 3 CAMS criteria. We also aimed to report our experience treating these patients at high risk with annual total cutaneous examination, total cutaneous photography, and dermoscopy. METHODS: Consecutive medical records from a private dermatology practice were reviewed. A total of 258 patients were selected who fulfilled the criteria of having: (1) total cutaneous photography as an aid for follow-up; (2) total cutaneous examination at least once per year; (3) at least 6 months of clinical follow-up; and (4) no personal history of melanomas. A total of 160 patients with CAMS and 98 with HRNCAMS were included in this study. The 10-year risk for MM developing in these 2 cohorts was computed using the Kaplan-Meier method. RESULTS: In the CAMS cohort, 28 new MMs developed in 19 patients resulting in a cumulative 10-year risk of 14% (95% confidence interval: 7-20). In the HRNCAMS cohort, 10 new MMs developed in 9 patients, and the cumulative 10-year risk was 10% (95% confidence interval: 2-17). The difference between the 2 groups was not statistically significant (P=.91). The MMs diagnosed in both cohorts were either in situ or less than 1 mm in Breslow thickness. There were no MM metastases or MM-related deaths in either cohort during a mean follow-up period of 120 months for the CAMS and 98 months for the HRNCAMS group. CONCLUSION: Both the patients with CAMS and HRNCAMS were at very high risk for MMs developing. The combination of total cutaneous photography, total cutaneous examination, and dermoscopy were used in treating our patients. No MM 1 mm or greater in thickness developed during follow-up in either group
— id: 44749, year: 2004, vol: 50, page: 15, stat: Journal Article,

Circulating enterolactone and risk of breast cancer: a prospective study in New York
Zeleniuch-Jacquotte, A; Adlercreutz, H; Shore, R E; Koenig, K L; Kato, I; Arslan, A A; Toniolo, P
2004 Jul 5;91(1):99-105, British journal of cancer
It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.British Journal of Cancer (2004) 91, 99-105. doi:10.1038/sj.bjc.6601893 www.bjcancer.com
— id: 43220, year: 2004, vol: 91, page: 99, stat: Journal Article,

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study
Zeleniuch-Jacquotte, A; Shore, R E; Koenig, K L; Akhmedkhanov, A; Afanasyeva, Y; Kato, I; Kim, M Y; Rinaldi, S; Kaaks, R; Toniolo, P
2004 Jan 12;90(1):153-159, British journal of cancer
We assessed the association of sex hormone levels with breast cancer risk in a case-control study nested within the cohort of 7054 New York University (NYU) Women's Health Study participants who were postmenopausal at entry. The study includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and 563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for breast cancer for the highest quintile of each hormone and sex-hormone binding globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47-4.21), P(trend)=0.003 for oestradiol; 3.24 (1.87-5.58), P(trend)<0.001 for oestrone; 2.37 (1.39-4.04), P(trend)=0.002 for testosterone; 2.07 (1.28-3.33), P(trend)<0.001 for androstenedione; 1.74 (1.05-2.89), P(trend)<0.001 for dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31-0.82), P(trend)<0.001 for SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years prior to diagnosis showed results in the same direction as overall analyses, although the tests for trend did not reach statistical significance for DHEAS and SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95 cases and their matched controls who had given a second blood donation within 5 years of diagnosis, were of small magnitude and overall not different in cases and controls. The association of androgens with risk did not persist after adjustment for oestrone (1.08, 95% CI=0.92-1.26 for testosterone; 1.15, 95% CI=0.95-1.39 for androstenedione and 1.06, 95% CI=0.90-1.26 for DHEAS), the oestrogen most strongly associated with risk in our study. Our results support the hypothesis that the associations of circulating oestrogens with breast cancer risk are more likely due to an effect of circulating hormones on the development of cancer than to elevations induced by the tumour. They also suggest that the contribution of androgens to risk is largely through their role as substrates for oestrogen production
— id: 42623, year: 2004, vol: 90, page: 153, stat: Journal Article,

History of antibiotic use and risk of non-Hodgkin's lymphoma (NHL)
Kato, Ikuko; Koenig, Karen L; Baptiste, Mark S; Lillquist, Patricia P; Frizzera, Glauco; Burke, Jerome S; Watanabe, Hiroko; Shore, Roy E
2003 Oct 20;107(1):99-105, International journal of cancer
A population-based, incidence case-control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non-Hodgkin's lymphoma (NHL). Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records. Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2-20 years before the interview. The ORs for the highest exposure categories, >/=36 episodes and >/=366 days of use, were 2.56 (95% CI 1.33-4.94) and 2.66 (95% CI 1.35-5.27), respectively. These associations were primarily due to antibiotic use against respiratory infections and dental conditions. Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B-cell lymphoma and for respiratory tract lymphoma. Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks. Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL. However, a direct role of antibiotics in NHL induction has not been ruled out
— id: 38443, year: 2003, vol: 107, page: 99, stat: Journal Article,

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women
Key, T J; Appleby, P N; Reeves, G K; Roddam, A; Dorgan, J F; Longcope, C; Stanczyk, F Z; Stephenson, H E Jr; Falk, R T; Miller, R; Schatzkin, A; Allen, D S; Fentiman, I S; Key, T J; Wang, D Y; Dowsett, M; Thomas, H V; Hankinson, S E; Toniolo, P; Akhmedkhanov, A; Koenig, K; Shore, R E; Zeleniuch-Jacquotte, A; Berrino, F; Muti, P; Micheli, A; Krogh, V; Sieri, S; Pala, V; Venturelli, E; Secreto, G; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Kuller, L H; Cummings, S R; Helzlsouer, K J; Alberg, A J; Bush, T L; Comstock, G W; Gordon, G B; Miller, S R; Longcope, C
2003 Aug 20;95(16):1218-1226, Journal of the National Cancer Institute
BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol
— id: 38442, year: 2003, vol: 95, page: 1218, stat: Journal Article,

Free estradiol and breast cancer risk in postmenopausal women: Comparison of measured and calculated values
Key, TJ; Appleby, PN; Reeves, GK; Roddam, AW; Dorgan, JF; Longcope, C; Stanczyk, FZ; Stephenson, HE; Falk, RT; Miller, R; Schatzkin, A; Allen, DS; Fentiman, IS; Key, TJ; Wang, DY; Thomas, HV; Hankinson, SE; Toniolo, P; Akhmedkhanov, A; Koenig, K; Shore, RE; Zeleniuch-Jacquotte, A; Berrino, F; Muti, P; Krogh, AMV; Sieri, S; Pala, V; Venturelli, E; Secreto, G; Barrett-Connor, E; Laughlin, GA; Kabuto, M; Stevens, RG; Neriishi, K; Land, CE; Cauley, JA; Kuller, LH; Helzlsouer, KJ; Alberg, AJ; Bush, TL; Comstock, GW; Gordon, GB; Miller, SR; Longcope, C
2003 DEC ;12(12):1457-1461, Cancer epidemiology biomarkers & prevention
Mathematical methods exist to determine the fractions of sex hormones bound to albumin, bound to sex hormone binding globulin (SHBG), or unbound, using total hormone concentration and SHBG concentration. We used data from eight prospective studies of postmenopausal women to assess the validity of these estimates for fractions of estradiol (E2) and to investigate the impact of using calculated values in breast cancer relative risk (RR) models. Comparisons were made between measured and calculated concentrations of free and non-SHBG-bound E2 in four studies. Relationships between the hormone fractions were investigated and a sensitivity analysis of the calculation performed. Breast cancer RRs were estimated using conditional logistic regression by quintiles of free E2. There is a high correlation (r > 0.91) between calculated and measured values of both free and non-SHBG-bound E2. The calculation is highly sensitive to total hormone concentration but is relatively insensitive to SHBG concentration. In studies with both measured and calculated values, the RRs of breast cancer by quintile of free E2 were almost identical for both estimates; using calculated values in all possible studies the RR in the highest compared with the lowest quintile of free E2 was 2.29 (95% confidence interval, 1.65-3.19). The mathematical method used to calculate fractions of E2 is valid, and RR analyses using calculated values produce similar results to those using measured values. This suggests that for epidemiological studies, it is only necessary to measure total E2 concentration and SHBG concentration, with hormone fractions being obtained by calculation, producing savings in cost, time, and serum
— id: 42543, year: 2003, vol: 12, page: 1457, stat: Journal Article,

Aspirin and lung cancer in women
Akhmedkhanov, A; Toniolo, P; Zeleniuch-Jacquotte, A; Koenig, K L; Shore, R E
2002 Jul 1;87(1):49-53, British journal of cancer
The association between aspirin use and lung cancer risk in women was examined in a case-control study nested in the New York University Women's Health Study, a large cohort in New York. Case subjects were all the 81 incident lung cancer cases who had provided information about aspirin use at enrollment and during the 1994-1996 follow up. Ten controls per case were randomly selected from among study participants who matched a case by age, menopausal status, and dates of enrollment and follow-up. Relative to no aspirin use, the odds ratio for lung cancer (all histological sub-types combined) among subjects who reported aspirin use three or more times per week for at least 6 months was 0.66 (95% confidence interval 0.34-1.28), after adjustment for smoking and education. A stronger inverse association was observed in analyses restricted to non-small cell lung cancer (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.96). These results suggest that regular aspirin use might be inversely associated with risk of lung cancer in women, particularly the non-small cell sub-type
— id: 32489, year: 2002, vol: 87, page: 49, stat: Journal Article,

Management of Spitz nevi: a survey of dermatologists in the United States
Gelbard, Sandra N; Tripp, Jackie M; Marghoob, Ashfaq A; Kopf, Alfred W; Koenig, Karen L; Kim, John Y; Bart, Robert S
2002 Aug;47(2):224-230, Journal of the American Academy of Dermatology
BACKGROUND: There is no consensus concerning management of Spitz nevi. OBJECTIVE: This study was carried out to ascertain how dermatologists manage Spitz nevi. METHODS: A questionnaire was sent to 997 fellows of the American Academy of Dermatology, 284 pediatric dermatologists, and 27 directors of pigmented-lesion clinics. The results are based on the 381 questionnaires returned. RESULTS: The vast majority of responding dermatologists (93%) recommend biopsies of suspected Spitz nevi. Of this group, 43% recommend total biopsies and 55% recommend partial biopsies; 2% would recommend either total or partial biopsies, depending on the clinical situation. Sixty-nine percent of physicians would completely excise a lesion that was histologically diagnosed as an incompletely removed Spitz nevus. Seventy percent of general dermatologists and 80% of pediatric dermatologists would recommend excision with a 1- to 2-mm margin of normal-appearing skin around a Spitz nevus. Nine percent of general dermatologists would recommend margins of 4 mm or more; however, all pediatric dermatologists surveyed would recommend margins less than 4 mm. Physicians were less likely to monitor patients whose Spitz nevi were completely removed. Three fourths (74%) of respondents believe Spitz nevi are entirely benign, 4% believe they are precursors to melanoma, and 22% are not sure. Seven percent of general dermatologists and 4% of pediatric dermatologists have seen metastatic melanomas arise at sites of lesions initially diagnosed histologically as Spitz nevi; 40% of pigmented-lesion clinic directors have seen such lesions. CONCLUSIONS: We believe that the lack of consensus, both in our survey and in the medical literature, reflects to some extent the lack of certainty in the histologic differentiation of Spitz nevi from melanomas and that concern about melanoma influences management. At the pigmented-lesion clinic of the New York University Skin and Cancer Unit, because of this concern about melanoma, it is usually recommended that Spitz nevi be completely excised
— id: 32468, year: 2002, vol: 47, page: 224, stat: Journal Article,

Use of anti-inflammatory and non-narcotic analgesic drugs and risk of non-Hodgkin's lymphoma (NHL) (United States)
Kato, Ikuko; Koenig, Karen L; Shore, Roy E; Baptiste, Mark S; Lillquist, Patricia P; Frizzera, Glauco; Burke, Jerome S; Watanabe, Hiroko
2002 Dec;13(10):965-974, Cancer causes & control. ccc
OBJECTIVE: To examine whether exposures to anti-inflammatory and non-narcotic analgesic drugs are associated with risk of non-Hodgkin's lymphoma (NHL). METHODS: A case-control study was conducted among women living in upstate New York. The study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls randomly selected from the Medicare beneficiary files and New York State driver's license records. Information regarding use of common medications in the past 20 years and potential confounding variables was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model. RESULTS: There were non-significant increases in risk associated with ever use of cortisone injections and oral cortisone (OR = 1.44 (CI 0.98-2.11) for injections and 1.21 (CI 0.73-2.00) for oral cortisone, although there was no clear dose-response relationship with either type. On the other hand, the risk of NHL progressively increased with the frequency of use of non-steroidal anti-inflammatory and non-narcotic analgesic drugs (NSAID/NNAD) (p-value for trend 0.008). Women who used any of these medications daily for more than 10 years had an OR of 1.90 (CI 1.01-3.57), compared with those who used it less than once a month on average. The risk associated with long-term use was most pronounced for ibuprofen, intermediate for aspirin, and least for acetaminophen. CONCLUSIONS: Because the population-attributable risk associated with NSAID/NNAD use is potentially large, our results need to be verified in further epidemiologic studies
— id: 38444, year: 2002, vol: 13, page: 965, stat: Journal Article,

Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies
Key, T; Appleby, P; Barnes, I; Reeves, G
2002 Apr 17;94(8):606-616, Journal of the National Cancer Institute
BACKGROUND: Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk. We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women. METHODS: We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not. None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels. The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case-control sets matched within each study. Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate. RESULTS: The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21 (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to 2.71; P(trend)<.001); the RRs for women with increasing quintiles of free estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24 (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The magnitudes of risk associated with the other estrogens and with the androgens were similar. SHBG was associated with a decrease in breast cancer risk (P(trend) =.041). The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis. CONCLUSION: Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women
— id: 38580, year: 2002, vol: 94, page: 606, stat: Journal Article,

Aspirin and epithelial ovarian cancer
Akhmedkhanov A; Toniolo P; Zeleniuch-Jacquotte A; Kato I; Koenig KL; Shore RE
2001 Dec;33(6):682-687, Preventive medicine
BACKGROUND: Epidemiological evidence suggests that chronic inflammation may influence ovarian carcinogenesis. The study objective was to examine the association between the commonly used anti-inflammatory drug aspirin and epithelial ovarian cancer. METHODS: The authors conducted a case-control study based in the New York University Women's Health Study cohort enrolled between 1985 and 1991 in New York City. After a median follow-up period of 12 years, 68 incident cases of epithelial ovarian cancer were identified. Data about regular aspirin use were collected during the 1994-1996 follow-up questionnaire. Using a case-control study design, 10 controls per case were randomly selected among study participants who matched the case by age and menopausal status. Conditional logistic regression analysis was used to study the relationships between aspirin and epithelial ovarian cancer by generating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Relative to no aspirin use, the OR for epithelial ovarian cancer among women who reported aspirin use three or more times per week for a period of at least 6 months was 0.60 (95% CI 0.26, 1.38), after adjustment for age at menarche, parity, oral contraceptive use, and first-degree family history of breast cancer before age 50. Among recent, within the previous 5 years, users of aspirin, the adjusted OR was 0.36 (95% CI 0.11, 1.18). CONCLUSION: Although confidence intervals included unity, the observed risk estimates seem to be compatible with previous studies suggesting that regular aspirin use could be inversely associated with risk of epithelial ovarian cancer
— id: 26517, year: 2001, vol: 33, page: 682, stat: Journal Article,

Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study
Zeleniuch-Jacquotte A; Akhmedkhanov A; Kato I; Koenig KL; Shore RE; Kim MY; Levitz M; Mittal KR; Raju U; Banerjee S; Toniolo P
2001 Apr 6;84(7):975-981, British journal of cancer
We assessed the association of postmenopausal serum levels of oestrogens and sex hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control study nested within the NYU Women's Health Study cohort. Among 7054 women postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a median of 5.5 years after blood donation. Each case was compared to 4 controls matched on age, menopausal status at enrolment, and serum storage duration. Endometrial cancer risk increased with higher levels of oestradiol (odds ratio = 2.4 in highest vs lowest tertile, P for trend = 0.02), percent free oestradiol (OR = 3.5, P< 0.001), and oestrone (OR = 3.9, P< 0.001). Risk decreased with higher levels of percent SHBG-bound oestradiol (OR = 0.43, P = 0.03) and SHBG (OR = 0.39, P = 0.01). Trends remained in the same directions after adjusting for height and body mass index. A positive association of body mass index with risk was substantially reduced after adjusting for oestrone level. Our results indicate that risk of endometrial cancer increases with increasing postmenopausal oestrogen levels but do not provide strong support for a role of body mass index independent of its effect on oestrogen levels.
— id: 21217, year: 2001, vol: 84, page: 975, stat: Journal Article,

Large congenital melanocytic nevi and the risk for development of malignant melanoma and neurocutaneous melanocytosis
Bittencourt FV; Marghoob AA; Kopf AW; Koenig KL; Bart RS
2000 Oct;106(4):736-741, Pediatrics
OBJECTIVE: To determine the risk for developing malignant melanoma and neurocutaneous melanocytosis (NCM) in patients with large congenital melanocytic nevi. DESIGN: Follow-up data suitable for calculations were available on 160 patients in the New York University Registry of Large Congenital Melanocytic Nevi who had been free of known melanomas or NCM when entered into the Registry. The cumulative 5-year life-table risks for developing melanoma and NCM were calculated. The relative risk for developing melanoma, using a control general population reference group, was determined. RESULTS: The 160 patients (median age at entry: 14 months) were followed prospectively for an average of 5.5 years. Three extracutaneous melanomas developed: 2 were in the central nervous system (CNS) and 1 was retroperitoneal. The 5-year cumulative life-table risk for developing melanoma was 2.3% (95% confidence interval [CI]:.8-6.6) and the relative risk was 101 (95% CI: 21-296). No melanoma occurred within a large congenital melanocytic nevus. Four patients developed manifest NCM, 2 with CNS melanomas. The 5-year cumulative life-table risk for developing NCM was 2.5% (95% CI:.8-7.2). Ten patients were excluded from the calculations because of preexisting disease on entry into the Registry: 5 with manifest NCM and 5 with melanomas (3 in large congenital melanocytic nevi, 1 in nonnevus skin, and 1 unknown primary). CONCLUSIONS: Patients with large congenital melanocytic nevi are at increased risk for developing melanomas. There is also a significant increased risk for developing NCM. The high incidence of CNS involvement may influence decisions concerning treatment of the large congenital melanocytic nevi
— id: 26839, year: 2000, vol: 106, page: 736, stat: Journal Article,

Risk of iron overload among middle-aged women
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
2000 May;70(3):119-125, International journal for vitamin & nutrition research
Iron overload, expressed as increased body iron stores, has been recognized as a potential hazard because it promotes the generation of oxygen radicals. We analyzed factors associated with serum ferritin levels (an indicator of body iron stores) among middle-aged women with a high prevalence of nutrient supplement use. Serum ferritin concentrations were determined on automated immunoassay for 487 healthy women with the mean age of 57 years who participated in the New York University Women's Health Study. The mean serum ferritin concentration in postmenopausal women was more than twice that in premenopausal women. Serum ferritin concentrations progressively increased with advancing age, but adjustment for menopausal status considerably weakened this association. Among non-dietary factors, nonwhite ethnicity, obesity and cigarette smoking were positively associated with serum ferritin concentrations. After adjustment for these factors and for menopausal status, serum ferritin levels were positively associated with meat intake and multivitamin use and inversely associated with breakfast cereal consumption. However, none of these lifestyle factors positively associated with serum ferritin levels had a significant impact on serum ferritin levels above 100 ng/ml (approximately equal to median concentration). Our results suggest that iron overload seems unlikely among middle aged women through their diet and nutritional supplements
— id: 34554, year: 2000, vol: 70, page: 119, stat: Journal Article,

Diet, smoking and anthropometric indices and postmenopausal bone fractures: a prospective study
Kato I; Toniolo P; Zeleniuch-Jacquotte A; Shore RE; Koenig KL; Akhmedkhanov A; Riboli E
2000 Feb;29(1):85-92, International journal of epidemiology
OBJECTIVE: Bone fractures are an important cause of morbidity and mortality among the elderly in the US. The present study assesses the possible role of a number of risk factors for postmenopausal bone fractures. METHODS: We analysed the relationships of anthropometric, demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospective cohort study, the New York University Women's Health Study. RESULTS: After an average of 7.6 years of follow-up, 1025 new incident bone fractures were reported, including 34 hip and 159 wrist fractures (incidence rates; 71.6 and 334.7 per 105 woman-years, respectively). The risk of fracture increased with increasing age, body height and total fat intake, while it was significantly lower among obese and African American women. The relative risk among African Americans was 0.45 (95% CI: 0.32-0.63) compared with non-African Americans. Women taller than 170 cm had a 64% increase in risk of fractures, as compared with those under 155 cm. These associations were generally more pronounced when fractures were limited to those at the hip and wrist. CONCLUSIONS: The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity, short stature and African American ethnicity
— id: 10348, year: 2000, vol: 29, page: 85, stat: Journal Article,

Psychotropic medication use and risk of hormone-related cancers: the New York University Women's Health Study
Kato I; Zeleniuch-Jacquotte A; Toniolo PG; Akhmedkhanov A; Koenig K; Shore RE
2000 Jun;22(2):155-160, Journal of public health medicine
BACKGROUND: The use of psychotropic medications may increase the risk of hormone-related cancers in females through increased gonadotropin secretion, but the data from epidemiologic studies are limited to evaluate the hypothesis. METHODS: The association between the use of psychotropic medications and cancer incidence was studied in a prospective cohort study that involves 15,270 women who participated in mammographic screening. The relative risks (RR) and 95 per cent confidence intervals (CIs) for cancer associated with the use of psychotropic medications were estimated by the Cox's proportional hazard model. RESULTS: During an average of 7.3 years of follow-up, 1,130 incident cases of cancer were identified, including 566 breast, 67 endometrial and 47 ovarian cancers. The use of any type of psychotropic medication at baseline was associated with increased risks of breast [relative risk (RR) = 1.39, 95 per cent CI 1.11-1.74], endometrial (RR=1.71; 95 per cent CI 0.93-3.14) and ovarian (RR= 1.48, 95 per cent CI 0.69-3.16) cancers, whereas no increase in risk was observed for other cancers (RR = 1.06). When the subjects were divided by menopausal status at baseline, premenopausal women tended to have higher risk of all hormone-related cancers (RR = 1.73, 95 per cent CI 1.27-2.35) than postmenopausal women (RR=1.23, 95 per cent CI 0.94-1.62). The magnitude of the RR associated with the use of these medications did not change by length of follow-up. Analysis by type of medication did not find that the association was limited to specific types. CONCLUSION: The observed association needs to be confirmed in further studies based on more detailed medication history
— id: 34553, year: 2000, vol: 22, page: 155, stat: Journal Article,

Breslow thickness and clark level in melanoma: support for including level in pathology reports and in American Joint Committee on Cancer Staging
Marghoob AA; Koenig K; Bittencourt FV; Kopf AW; Bart RS
2000 Feb 1;88(3):589-595, Cancer
BACKGROUND: Thickness is known to be an important survival prognosticator for cutaneous melanoma, but controversy exists as to whether Clark level of invasion retains prognostic significance once thickness has been accounted for. A recent proposal to eliminate Clark level from the staging system for melanoma of the American Joint Committee on Cancer (AJCC) prompted the authors to investigate whether level adds useful prognostic information to Breslow thickness. They used the data base of the New York University Melanoma Cooperative Group (NYU-MCG) Registry. METHODS: The analysis was based on 919 patients with AJCC Stage I or II melanomas diagnosed between 1972 and 1982 and followed for an average of 10.9 years. Melanoma thicknesses were divided into 4 categories (< or = 0.75, 0.76-1.50, 1.51-4.00, and >4.00 mm). Patients were cross-classified according to tumor thickness and Clark level (II-V). For each combination of thickness and level, the Kaplan-Meier survival curve and 10-year survival proportion were computed, using death from melanoma as the outcome. The impact of Clark level on survival was evaluated for each of the thickness categories. The Cox proportional hazards model was used to assess the simultaneous effect of thickness and level on survival while controlling for other important prognostic factors, i.e., age, tumor location, and presence or absence of ulceration. RESULTS: Level of invasion was a significant predictor of death from melanoma in each of the four thickness categories. Likewise, in the Cox analyses, level was a significant prognostic variable, even after thickness was included in the model and regardless of whether thickness was treated as a categoric or a continuous variable. CONCLUSIONS: These results confirm that both tumor thickness and level of invasion are important independent prognostic factors in AJCC Stage I and II melanomas. The authors recommend that Clark levels be kept as criteria in the AJCC staging system and be included in pathology reports. [See editorial on pages 491-6, this issue.]
— id: 49383, year: 2000, vol: 88, page: 589, stat: Journal Article,

Serum insulin-like growth factor-I and breast cancer
Toniolo P; Bruning PF; Akhmedkhanov A; Bonfrer JM; Koenig KL; Lukanova A; Shore RE; Zeleniuch-Jacquotte A
2000 Dec 1;88(5):828-832, International journal of cancer
Insulin-like growth factor I (IGF-I) is a systemic hormone with potent mitogenic and anti-apoptotic properties, which could influence the proliferative behavior of normal breast cells. Limited epidemiological observations suggest that the hormone may play a role in the etiology of breast cancer, especially at pre-menopausal ages. In a prospective case-control study nested within a cohort of New York City women, IGF-I, IGF-binding protein 3 (IGFBP-3) and C peptide were measured in frozen serum samples from 172 pre-menopausal and 115 post-menopausal subjects who were subsequently diagnosed with breast cancer. Subjects were eligible if diagnosed 6 months or more after recruitment into the study (7 to 120 months). Cohort members who matched the cases on age, menopausal status, date of blood sampling and day of menstrual cycle at blood collection served as controls. Post-menopausal breast cancer was not associated with serum IGF-I, IGFBP-3 or C-peptide levels. However, the risk of breast cancer increased with increasing serum concentrations of IGF-I in pre-menopausal women. The odds ratio (OR) for the highest quartile of IGF-I (>256 ng/ml) compared to the lowest (<168 ng/ml) was 1.60 [95% confidence interval (CI) 0.91-2. 81]. The OR decreased to 1.49 (95% CI 0.80-2.79) after adjustment for IGFBP-3. In analyses restricted to subjects who were pre-menopausal at the time of blood sampling and whose cancer was diagnosed before age 50, the top vs. bottom quartile OR increased appreciably to 2.30 (95% CI 1.07-4.94). Adjustment for IGFBP-3 reduced the OR to 1.90 (95% CI 0.82-4.42). There was no association between pre-menopausal breast cancer and IGFBP-3, IGF-I:IGFBP-3 ratio or non-fasting levels of C peptide. Elevated circulating levels of IGF-I may be an indicator of increased risk of breast cancer occurring before age 50
— id: 34550, year: 2000, vol: 88, page: 828, stat: Journal Article,

Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Akhmedkhanov A; Zeleniuch-Jacquotte A; Riboli E
1999 Apr;79(11-12):1917-1922, British journal of cancer
Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case-control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92-4.29). The potentially protective effects of folate need to be confirmed in clinical trials
— id: 6090, year: 1999, vol: 79, page: 1917, stat: Journal Article,

Epidemiologic correlates of serum folate and homocysteine levels among users and non-users of vitamin supplement
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
1999 Sep;69(5):322-329, International journal for vitamin & nutrition research
Lower serum folate and higher serum homocysteine levels are known risk factors for various conditions. Thus, epidemiologic correlates with these measurements were studied for 256 multivitamin users and 230 non-users who were middle-aged women. Both serum folate and homocysteine levels increased with advancing age in both multivitamin users (P < 0.01 and P < 0.01) and non-users (P = 0.08 and P < 0.01). Among non-users, higher intake of vegetables, fruits, cold cereals and total protein were associated positively with serum folate and inversely with homocysteine levels. There were 25-74% increases in serum folate and 10-15% decreases in serum homocysteine between 1st and 4th quartiles of intake of these food/nutrients. In addition, 26% lower serum folate and 18% higher serum homocysteine were observed for those smoking 20 or more cigarettes per day compared with non-smokers. Among multivitamin users, body weight was correlated inversely with serum folate (P < 0.01) and positively with serum homocysteine levels (P = 0.04), while no correlates were found among lifestyle factors. Regular use of multivitamins increased serum folate about fourfold and decreased homocysteine twofold. These results suggest that multivitamin use can offset the effects of an unhealthy lifestyle on these serum markers, and that levels of serum folate and homocysteine can also be favorably influenced by healthier diet and abstinence from smoking
— id: 6221, year: 1999, vol: 69, page: 322, stat: Journal Article,

Iron intake, body iron stores and colorectal cancer risk in women: a nested case-control study
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
1999 Mar 1;80(5):693-698, International journal of cancer
Accumulated evidence suggests that increased body iron stores may increase the risk of colorectal cancer, possibly via catalyzing oxidation reactions. We examined the relationship between iron status and colorectal cancer in a case-control study nested within the New York University Women's Health Study cohort. For 105 incident cases of colorectal cancer with an average follow-up of 4.7 years and 523 individually matched controls, baseline levels of serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation were determined as indicators of body iron stores, and total iron intake was assessed based on their diet and supplement intake. Overall, there were no associations between the risk of colorectal cancer and any of these indices except for serum ferritin, which showed a significant inverse association. When analyzed by subsite, there was an increasing trend in risk of cancer of the proximal colon with increasing total iron intake (p-value for trend = 0.04). In addition, a significantly increased risk of colorectal cancer associated with higher total iron intake [odds ratio (OR) = 2.50; 95% confidence interval (CI): 1.06-5.87] was observed among subjects with higher intake of total fat. Our results do not support a role of increased body iron stores in the development of colorectal cancer, but suggest that luminal exposure to excessive iron may possibly increase the risk in combination with a high fat diet
— id: 7363, year: 1999, vol: 80, page: 693, stat: Journal Article,

Comparison of active and cancer registry-based follow-up for breast cancer in a prospective cohort study
Kato I; Toniolo P; Koenig KL; Kahn A; Schymura M; Zeleniuch-Jacquotte A
1999 Feb 15;149(4):372-378, American journal of epidemiology
The authors compared the relative effectiveness of two distinct follow-up designs in prospective cohort studies--the active approach, based on direct contact with study subjects, and the passive approach, based on record linkages with population-based cancer registries--utilizing available information from the New York University Women's Health Study (WHS) and the New York State Cancer Registry (NYSCR). The analyses were limited to breast cancer cases identified during the period 1985-1992, for which follow-up was considered reasonably complete by both the WHS and the NYSCR. Among 12,947 cohort members who reported a New York State address, 303 pathologically confirmed cases were identified through active follow-up and 284 through record linkage. Sixty-three percent of cancers were identified by both sources, 21% by the WHS only, and 16% by the NYSCR only. The agreement was appreciably better for invasive cancers. The percentage of cases identified only by the NYSCR was increased among subjects whose active follow-up was incomplete, as well as among nonwhites, obese patients, and parous patients. This suggests that relying on either type of follow-up alone may introduce certain biases in evaluating risk factors for breast cancer. Combining both approaches appears to be a better strategy in prospective cohort studies
— id: 7364, year: 1999, vol: 149, page: 372, stat: Journal Article,

Epidemiologic correlates with menstrual cycle length in middle aged women
Kato I; Toniolo P; Koenig KL; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
1999 Oct;15(9):809-814, European journal of epidemiology
While irregular menstruations have been associated with lower cumulative exposure to the ovarian steroids, shorter regular cycles have been postulated to increase the cumulative exposure. Epidemiological correlates with menstrual patterns were analyzed among 4900 premenopausal women aged 45 or younger from the New York University Women's Health Study. The length of regular menstrual cycles increased with increasing age at menarche, body mass index and parity, but decreased with age, nonwhite racial background and current smoking. The likelihood of irregular cycles increased with increasing age, body mass index and number of cigarettes smoked per day. With adjustment for age, body mass index and number of cigarettes smoked per day, the risk of irregular cycles was marginally positively associated with total fat intake
— id: 10358, year: 1999, vol: 15, page: 809, stat: Journal Article,

Onset of natural menopause - Response
Kato, I; Toniolo, P; Akhmedkhanov, A; Koenig, KL; Shore, R; Zeleniuch-Jacquotte, A
1999 DEC ;52(12):1291-1292, Journal of clinical epidemiology
— id: 53844, year: 1999, vol: 52, page: 1291, stat: Journal Article,

Body fat distribution and obesity in pre- and postmenopausal breast cancer
Sonnenschein E; Toniolo P; Terry MB; Bruning PF; Kato I; Koenig KL; Shore RE
1999 Dec;28(6):1026-1031, International journal of epidemiology
BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight
— id: 10351, year: 1999, vol: 28, page: 1026, stat: Journal Article,

Buffering capacity of coal and its acid-soluble Fe2+ content: possible role in coal workers' pneumoconiosis
Huang X; Fournier J; Koenig K; Chen LC
1998 Jul;11(7):722-729, Chemical research in toxicology
Epidemiological studies have shown that the prevalence of coal workers' pneumoconiosis (CWP) differed remarkably between different coal mine regions despite comparable exposures to respirable dust. In the United States, CWP was found to be most common in Pennsylvania coal miners and least common in miners from Utah. The active component(s) responsible for the regional differences in CWP has not yet been identified. In the present study, we found that coals from Pennsylvania, compared with Utah coals, showed a much lower buffering capacity as determined by the amount of acid consumed in order to reach pH 4.5, which is the pH of the phagolysosomes of macrophages. Moreover, the coals from Pennsylvania released large amounts of Fe2+ in the acidified extract, whereas the coals from Utah released little Fe2+. Using electron spin resonance (ESR), we found that the coals from Pennsylvania, but not from Utah, were effective in oxidizing formate by a radical pathway. Two coals, one from Utah with high buffering capacity and low acid-soluble Fe2+ and the other from Pennsylvania with low buffering capacity and high acid-soluble Fe2+, were then selected for cell treatment. We found that human tracheal epithelial (HTE) cells treated with the coal from Pennsylvania (10 microg/cm2) showed a 36% increase in oxidant formation over the control as detected by dichlorofluorescein assay, whereas the coal from Utah had no effect. An electrophoretic mobility shift assay was used to test the binding affinity of nuclear proteins extracted from the coal-treated HTE cells to an oxidative stress-responsive transcription factor activator protein-1 (AP-1) element. The coal from Pennsylvania with high acid-soluble Fe2+ (1 microg/cm2) activated AP-1 to the same extent as 10 microM H2O2, while the coal from Utah without acid-soluble Fe2+ had no effect. These results support our hypothesis that the prevalence of CWP may be higher in coal workers exposed to coal with high acid-soluble Fe2+ and low buffering capacity than in workers exposed to coal with low acid-soluble Fe2+ and high buffering capacity
— id: 7609, year: 1998, vol: 11, page: 722, stat: Journal Article,

Prospective study of factors influencing the onset of natural menopause
Kato I; Toniolo P; Akhmedkhanov A; Koenig KL; Shore R; Zeleniuch-Jacquotte A
1998 Dec;51(12):1271-1276, Journal of clinical epidemiology
Late or early menopause has been implicated in risk of several chronic diseases in women. To study factors influencing the onset of natural menopause, the authors analyzed the follow-up data of 4694 premenopausal women who enrolled in the New York University Women Study at ages 34-61. In an average of 5.4 years of observation, there were 2035 incidences of menopause, with the median age of 51.3 years. Current smokers experienced menopause 0.75 years earlier than never-smokers. Those who smoked more than 10 cigarettes per day had a 40% increase in risk of earlier menopause. In contrast, women who had three or more children experienced menopause 0.86 years later than nulliparous women, and Jewish women, 0.66 years later than Catholic women. There was also a modest increase in the age at menopause with increasing body mass index. This prospective study provides solid epidemiologic evidence that several factors other than cigarette smoking have impact on the onset of natural menopause
— id: 6062, year: 1998, vol: 51, page: 1271, stat: Journal Article,

Pervasive developmental disorders: diagnosis, intervention and education
Koenig K
1998 ;2(8):154-28 Aug, American Journal for Nurse Practitioners
The child with a PDD presents a challenge to advanced practice nurses in diagnosis and intervention. Knowledge of the patterns of normal growth and development, with an emphasis on normal social and communicative development, is essential for identifying children with deficits. Children with PDDs need a broad range of intensive services, and extensive planning and coordination of these services is essential to support the best outcome for the child. In addition, parents need a knowledgeable professional to help with sorting through the myriad of assessment issues, consultation with specialists, and possibilities for intervention. The APN can play a pivotal role in providing coordination, education, and support to the child and family. <8>
— id: 48093, year: 1998, vol: 2, page: 154, stat: Journal Article,

Risk of melanoma in medium-sized congenital melanocytic nevi: a follow-up study
Sahin S; Levin L; Kopf AW; Rao BK; Triola M; Koenig K; Huang C; Bart R
1998 Sep;39(3):428-433, Journal of the American Academy of Dermatology
BACKGROUND: The risk of the occurrence of malignant melanoma (MM) in medium-sized (1.5 to 19.9 cm in diameter) congenital melanocytic nevi (CMN) is the subject of controversy. Universally accepted recommendations regarding the management of such lesions have not been made. OBJECTIVE: Our purpose was to assess the risk of MM arising in medium-sized CMN. METHODS: The study included 230 medium-sized CMN in 227 patients, first seen in a private dermatology practice from 1955 to 1996, who were followed up for MM arising within their CMNs. Criteria for entry into the study included (1) a clinically diagnosed medium-sized CMN, (2) minimum follow-up period of 1 year, and (3) a photograph of the lesion in the patient's medical record. RESULTS: No MM occurred in a medium-sized CMN during an average follow-up of 6.7 years (median, 5.8 years) to an average age of 25.5 years (median, 19.1 years). CONCLUSION: The results of this short-term follow-up study do not support the view that there is a clinically significantly increased risk for MM arising in banal-appearing medium-sized CMN or that prophylactic excision of all such lesions is mandatory. Lifelong medical observation seems a reasonable alternative for many medium-sized CMN
— id: 57244, year: 1998, vol: 39, page: 428, stat: Journal Article,

Prospective study of diet and female colorectal cancer: the New York University Women's Health Study
Kato I; Akhmedkhanov A; Koenig K; Toniolo PG; Shore RE; Riboli E
1997 ;28(3):276-281, Nutrition & cancer
The relation between diet and female colorectal cancer was analyzed in a prospective study of 14,727 women aged 34-65 years, who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991. They were followed through the end of 1994 (average 7.1 yrs) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries, resulting in 100 incident cases of colorectal cancer. There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories, total or subclasses of fat, carbohydrate, or dietary fiber, whereas there was an inverse association with total protein. Among major food groups, there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish (relative risk for 4th vs. 1st quartile = 0.49, 95% confidence interval = 0.27-0.89). A similar inverse association was also observed for consumption of dairy products, and this association was explained mainly by calcium, not by other nutrients, such as fat or protein. The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer, whereas the relations with red meat or total fat remained unclear
— id: 10362, year: 1997, vol: 28, page: 276, stat: Journal Article,

Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women
Zeleniuch-Jacquotte A; Bruning PF; Bonfrer JM; Koenig KL; Shore RE; Kim MY; Pasternack BS; Toniolo P
1997 Jun 1;145(11):1030-1038, American journal of epidemiology
The authors examined the relation between postmenopausal serum levels of testosterone and dehydroepiandrosterone sulfate (DHEAS) and subsequent risk of breast cancer in a case-control study nested within the New York University Women's Health Study cohort. A specific objective of their analysis was to examine whether androgens had an effect on breast cancer risk independent of their effect on the biologic availability of estrogen. A total of 130 cases of breast cancer were diagnosed prior to 1991 in a cohort of 7,054 postmenopausal women who had donated blood and completed questionnaires at a breast cancer screening clinic in New York City between 1985 and 1991. For each case, two controls were selected, matching the case on age at blood donation and length of storage of serum specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees C since sampling. The present report includes a subset of 85 matched sets, for whom at least 6 months had elapsed between blood donation and diagnosis of the case. In univariate analysis, testosterone was positively associated with breast cancer risk (odds ratio (OR) for the highest quartile = 2.7, 95% confidence interval (CI) 1.1-6.8, p < 0.05, test for trend). However, after including % estradiol bound to sex hormone-binding globulin (SHBG) and total estradiol in the statistical model, the odds ratios associated with higher levels of testosterone were considerably reduced, and there was no longer a significant trend (OR for the highest quartile = 1.2, 95% CI 0.4-3.5). Conversely, breast cancer risk remained positively associated with total estradiol levels (OR for the highest quartile = 2.9, 95% CI 1.0-8.3) and negatively associated with % estradiol bound to SHBG (OR for the highest quartile = 0.05, 95% CI 0.01-0.19) after adjustment for serum testosterone levels. These results are consistent with the hypothesis that testosterone has an indirect effect on breast cancer risk, via its influence on the amount of bioavailable estrogen. No evidence was found of an association between DHEAS and risk of breast cancer in postmenopausal women
— id: 7290, year: 1997, vol: 145, page: 1030, stat: Journal Article,

Chromatic and luminance systems deficits in glaucoma
Greenstein VC; Halevy D; Zaidi Q; Koenig KL; Ritch RH
1996 Feb;36(4):621-629, Vision research
The purpose of this study was to compare the effects of glaucoma, at different stages of the disease process, on the two color-opponent system and on the luminance system. Discrimination thresholds were measured along the two equiluminant cardinal color axes (RG and YV) and along an achromatic luminance axis (LD) in 27 patients with open-angle glaucoma (OAG) and in 13 glaucoma suspects. Patients with OAG showed increased thresholds along all three axes. The threshold increases correlated significantly with the level of visual field loss. For glaucoma suspects, thresholds were also increased along all three axes. A subgroup of patients with OAG, those with pigmentary glaucoma, showed minimal increases in threshold along the RG axis. To further investigate this finding an additional 15 patients, seven with primary OAG and eight with pigmentary glaucoma were run in a two-alternative forced-choice experiment. For patients with pigmentary glaucoma, thresholds were increased less along the RG axis. The results of the study for OAG patients and glaucoma suspects are consistent with deficits in the two color-opponent systems, and in the luminance system
— id: 56818, year: 1996, vol: 36, page: 621, stat: Journal Article,

Accelerated atherosclerosis in South Asian expatriates living in New York
Kathuria, N; Koenig, K; Schwartzbard, A; Mele, KA; Levin, RI
1996 MAR ;44(3):A312-A312, Journal of investigative medicine
— id: 52967, year: 1996, vol: 44, page: A312, stat: Journal Article,

Disaster nomenclature--a functional impact approach: the PICE system
Koenig, K L; Dinerman, N; Kuehl, A E
1996 Jul;3(7):723-727, Academic emergency medicine
A standard nomenclature that concisely describes any disaster is currently lacking. This article describes a model taxonomy system. Instead of the term 'disaster,' a root word 'PICE,' 'potential injury-creating event,' is used. Descriptive modifiers to account for all possible scenarios surround this root word, as illustrated. [table: see text] A modifier is chosen from each column and a stage is assigned to each PICE. Column A describes the potential for additional casualties. Column B describes whether resources are overwhelmed and, if so, whether they must simply be augmented (disruptive) or they must first be reconstituted (paralytic). Column C describes the extent of geographic involvement. 'Stage' refers strictly to the likelihood that outside medical assistance will be needed. Stage 0 means there is little chance, stage I means there is a small chance (place outside help on 'alert'), stage II means there is a moderate chance (place on 'standby'), and stage III means local medical resources are clearly overwhelmed (immediately dispatch outside resources, commit personnel, prepare remote hospitals). For example, a multiple vehicle crash in a large city would be a 'static, controlled, local PICE, stage 0.' In conclusion, a new nomenclature for describing disasters is reported. A short phrase describes the incident and communicates the need for outside assistance. The model may be useful for disaster planning, management, and research
— id: 129898, year: 1996, vol: 3, page: 723, stat: Journal Article,

Estimating the reliability of an exposure variable in the presence of confounders
Kim MY; Pasternack BS; Carroll RJ; Koenig KL; Toniolo PG
1995 Jul 15;14(13):1437-1446, Statistics in medicine
In this paper we discuss estimation of the reliability of an exposure variable in the presence of confounders measured without error. We give an explicit formula that shows how the exposure becomes less reliable as the degree of correlation between the exposure and confounders increases. We also discuss biases in the corresponding logistic regression estimates and methods for correction. Data from a matched case-control study of hormone levels and risk of breast cancer are used to illustrate the methods
— id: 6921, year: 1995, vol: 14, page: 1437, stat: Journal Article,

A PROSPECTIVE-STUDY OF ENDOGENOUS ESTROGENS AND BREAST-CANCER IN POSTMENOPAUSAL WOMEN - REPLY
LEVITZ, M; BANERJEE, S; KOENIG, K; SHORE, RE; TONIOLO, P; ZELENIUCHJACQUOTTE, A
1995 SEP 20 ;87(18):1414-1415, Journal of the National Cancer Institute
— id: 86758, year: 1995, vol: 87, page: 1414, stat: Journal Article,

RE - PREMENOPAUSAL ESTRADIOL LEVELS AND THE RISK OF BREAST-CANCER - A NEW METHOD OF CONTROLLING FOR DAY OF THE MENSTRUAL-CYCLE - REPLY
PASTERNACK, BS; SHORE, RE; KOENIG, KL; TONIOLO, PG; ROSENBERG, CR
1995 APR 15 ;141(8):789-790, American journal of epidemiology
— id: 87373, year: 1995, vol: 141, page: 789, stat: Journal Article,

Is dermatologic usage of coal tar carcinogenic? A review of the literature
Pion IA; Koenig KL; Lim HW
1995 Mar;21(3):227-231, Dermatologic surgery
BACKGROUND. Coal tar ointments have been used for decades in the treatment of various dermatoses, most notably eczema and psoriasis. Occupational exposure to coal tar poses an increased risk of developing cutaneous malignancies. The evidence of an increased risk of skin cancer in humans, as a result of dermatologic usage of tar, however, is conflicting. OBJECTIVE. A consensus on the carcinogenicity of tar is sought. METHODS. The existing literature (in vitro, animal, and human studies) on this subject is reviewed. RESULTS. The carcinogenicity of coal tar has clearly been demonstrated by in vitro and animal studies, and appears to be potentiated by concomitant use of ultraviolet radiation. Systemic absorption of mutagens from topically applied tar has been demonstrated in humans. Epidemiologic studies in humans, however, have not definitively shown an increase in skin cancer with therapeutic use of tar. CONCLUSIONS. Conclusive evidence for the carcinogenicity of tar used in dermatologic practice is lacking. Further controlled studies are necessary
— id: 16746, year: 1995, vol: 21, page: 227, stat: Journal Article,

A prospective study of endogenous estrogens and breast cancer in postmenopausal women
Toniolo PG; Levitz M; Zeleniuch-Jacquotte A; Banerjee S; Koenig KL; Shore RE; Strax P; Pasternack BS
1995 Feb 1;87(3):190-197, Journal of the National Cancer Institute
BACKGROUND: Circumstantial evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue. PURPOSE: Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease. METHODS: The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14,291 New York City women, 35-65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5 1/2 years of study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35,509 person-years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at -80 degrees C since sampling. RESULTS: For increasing quartiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend = .06); the ORs for increasing quartiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend = .06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4, 3.0, and 2.9 (P value for trend < .01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend < .01), thus suggesting a strong protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn 2 or more years before breast cancer diagnosis. CONCLUSIONS: These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer. IMPLICATIONS: Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman's risk of developing breast cancer later in life
— id: 57459, year: 1995, vol: 87, page: 190, stat: Journal Article,

Endogenous estrogens and risk of breast cancer by estrogen receptor status: a prospective study in postmenopausal women
Zeleniuch-Jacquotte A; Toniolo P; Levitz M; Shore RE; Koenig KL; Banerjee S; Strax P; Pasternack BS
1995 Dec;4(8):857-860, Cancer epidemiology biomarkers & prevention
A positive association between postmenopausal serum levels of total estradiol, percentage of free estradiol, and percentage of estradiol not bound to sex hormone-binding globulin (SHBG) and breast cancer risk was recently reported by the New York University Women's Health Study (P. Toniolo et al., J. Natl. Cancer Inst., 87: 190-197, 1995). Data from this prospective study are used to assess whether the observed associations differ according to estrogen receptor (ER) status of the tumor. Between 1985 and 1991, 7063 postmenopausal women donated blood and completed questionnaires at a large breast cancer screening clinic in New York City. Before 1991, 130 cases of first primary breast cancer were identified by active follow-up of the cohort. For each case, two controls were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees since sampling. ER information was abstracted from pathology reports. Separate statistical analyses were conducted of ER-positive, ER-negative, and ER-unknown groups (53, 23, and 54 matched sets, respectively). In each of the 3 groups, the mean estradiol and the mean percentage of free estradiol were greater (21-28% and 6-7%, respectively) in cases than in controls. Conversely, the mean percentage of estradiol bound to SHBG was 9-12% lower in cases than in controls. The logistic regression coefficients measuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the ER-positive, ER-negative, and ER-unknown groups. These data suggest that in postmenopausal women, the association of endogenous estrogens with breast cancer risk is independent of the ER status of the tumor. This result is more compatible with the hypothesis of a progression from ER-positive to ER negative tumors than with the hypothesis that ER status identifies two distinct types of breast cancer
— id: 56859, year: 1995, vol: 4, page: 857, stat: Journal Article,

ENDOGENOUS ESTROGENS AND RISK OF BOAST CANCER BY ESTROGEN-RECEPTOR STATUS
ZELENIUCHJACQUOTTE, A; TONIOLO, P; LEVITZ, M; SHORE, R; KOENIG, K; BANERJEE, S; STRAX, P; PASTERNACK, B
1995 JUN 1 ;141(11):S15-S15, American journal of epidemiology
— id: 87280, year: 1995, vol: 141, page: S15, stat: Journal Article,

Premenopausal estradiol levels and the risk of breast cancer: a new method of controlling for day of the menstrual cycle [see comments]
Rosenberg CR; Pasternack BS; Shore RE; Koenig KL; Toniolo PG
1994 Sep 15;140(6):518-525, American journal of epidemiology
Levels of total estradiol in premenopausal women vary widely over the course of the menstrual cycle with a spike at the time of ovulation and dissimilar patterns pre- and post-ovulation. Evaluating the association between breast cancer and premenopausal measurements of total estradiol when the measurements cannot be taken on a uniform day of the cycle is therefore a difficult methodological challenge. In a matched case-control study of breast cancer nested within a prospective study, premenopausal serum samples obtained up to 7 years before breast cancer diagnosis were available for total estradiol assay. By fitting a three-piece spline model that regressed the logarithm of total estradiol (ln estradiol) on day of menstrual cycle, the authors were able to adjust the measurements for day of the cycle on which they were collected by expressing them in terms of the number of standard deviations above or below the fitted ln estradiol value for that day. Applying the adjusted measurements to the nested case-control study, they found evidence of a 1.5 to 2-fold risk for women in the upper two tertiles of ln estradiol relative to women in the lowest tertile. Conditional logistic regression analysis for day-of-cycle-adjusted ln estradiol treated as a continuous variable resulted in a relative risk estimate of 1.19 (95% confidence interval 0.91-1.55) per standard-deviation increase in adjusted ln estradiol
— id: 10268, year: 1994, vol: 140, page: 518, stat: Journal Article,

Propylene oxide mutagenesis at template cytosine residues
Snow ET; Singh J; Koenig KL; Solomon JJ
1994 ;23(4):274-280, Environmental & molecular mutagenesis
Propylene oxide (PO) is a widely used industrial reagent which is mutagenic and carcinogenic. We have recently shown that a variety of aliphatic epoxides, including propylene oxide, can react with DNA to form hydroxyalkyl adducts at N-3 of cytosine which rapidly undergo hydrolytic deamination to produce uracil adducts. These 3-hydroxyalkyl uracil adducts are stable in DNA and are postulated to be an important class of potentially mutagenic lesions. Mutagenesis at cytosine residues due to PO modification of single-stranded M13mp2/C141 DNA was studied by transfection of modified DNA into SOS and non-SOS induced E. coli host cells. Mutations of the proline (CCC) codon at C141 which result in reversion of the lacZ phenotype (blue plaques) were scored. It was found that PO treatment of single-stranded DNA results in dose-dependent mutagenesis that is highly SOS dependent. The spectrum of base-substitution mutations found at this site differed when PO-modified DNA was transfected into E. coli with different DNA repair backgrounds. These results indicate that propylene oxide induced DNA adducts at template cytosine residues are mutagenic in E. coli and that this mutagenesis is greatly increased by SOS processing. They also show that these lesions may be repaired by one or more mechanisms
— id: 6522, year: 1994, vol: 23, page: 274, stat: Journal Article,

Reliability of measurements of total, protein-bound, and unbound estradiol in serum
Toniolo P; Koenig KL; Pasternack BS; Banerjee S; Rosenberg C; Shore RE; Strax P; Levitz M
1994 Jan-Feb;3(1):47-50, Cancer epidemiology biomarkers & prevention
Estradiol (E2) circulates in the blood in three states: unbound (U-E2), bound to sex-hormone binding globulin (SHBG-E2), and bound to albumin. There is evidence to support the concept that only U-E2 and albumin-bound E2, are bioavailable (i.e., rapidly extracted by tissues). A case-control study nested within a large cohort of women, in which we are examining the effect of estrogens on breast cancer risk, offered the opportunity to assess the reliability of measurements of E2, the percentage of SHBG-E2, and the percentage of U-E2 based on multiple annual serum specimens. Long-term (1-2 year) reliability, as estimated by the intraclass correlation coefficient, was assessed in a subgroup of 71 premenopausal and 77 postmenopausal controls for whom two or three serum specimens were assayed. In postmenopausal women the intraclass correlation coefficient for a single measurement of total E2 was only 0.51. As for the percentage of SHBG-E2, intraclass correlation coefficients were 0.83 and 0.94, and for U-E2, 0.72 and 0.77 in the premenopausal and postmenopausal groups, respectively. These data suggest that, whereas single determinations of total E2 are insufficient to reliably estimate a woman's true mean level, a single measurement of the percentage of SHBG-E2 or U-E2 is adequate to assess bioavailability of E2 in an epidemiological study, irrespective of day of the menstrual cycle
— id: 56598, year: 1994, vol: 3, page: 47, stat: Journal Article,

The low carcinogenicity of electron radiation relative to argon ions in rat skin
Burns FJ; Jin Y; Koenig KL; Hosselet S
1993 Aug;135(2):178-188, Radiation research
The carcinogenicity of electron radiation relative to argon ions in rat skin was examined, specifically investigating whether the linear-quadratic model is useful for predicting cancer yield for one type of radiation based on yields observed for a different type. Three experiments were conducted to obtain information on the relationship between cancer yield and the dose of electron radiation: (1) a conventional dose-response protocol where the number of rats per group was based on the expected tumor yield; (2) a multiple-fraction protocol designed to take advantage of yield additivity as a way to estimate carcinogenicity at lower doses; and (3) a protocol to examine the effect of age at the time of irradiation on the dose-response relationship for cancer induction. Published data on the induction of skin cancer in rats irradiated with electrons were reanalyzed and combined with results of the new experiments. Skin cancer yield versus dose for argon ions was consistent with the linear-quadratic model, but the cancer yield for electrons was considerably lower (by a factor of 6.7 at 10 Gy) than the prediction based on the linear-quadratic model. The cancer yield for electron radiation was better fitted by a dose-cubed power function than a linear-quadratic function. The results indicate a substantially lower carcinogenic effectiveness for electron radiation, especially at lower doses, in comparison to argon ions and suggest that electrons may cause cancer by a three-event pathway instead of the two-event pathway that is consistent with the results for argon ions
— id: 8237, year: 1993, vol: 135, page: 178, stat: Journal Article,

Reliability of serum prolactin measurements in women
Koenig KL; Toniolo P; Bruning PF; Bonfrer JM; Shore RE; Pasternack BS
1993 Sep-Oct;2(5):411-414, Cancer epidemiology biomarkers & prevention
Prolactin, a hormone indispensable for milk secretion, has been shown to enhance the development and growth of mammary tumors in rodents; however, its importance in human breast cancer is uncertain. Serum prolactin levels are known to fluctuate considerably under normal conditions, and lack of precision in the hormone measurements may have contributed to the largely negative findings in humans to date. The purpose of this study was to investigate the reliability of prolactin measurements in women using stored serum from an ongoing prospective study of breast cancer. Separate groups of postmenopausal and premenopausal women who donated multiple blood samples at approximately 1-year intervals were studied. The reliability of a single log prolactin determination, as measured by the intraclass correlation coefficient, was 0.76 for the postmenopausal women (95% confidence interval, 0.66-0.85) and 0.48 for the premenopausal women (95% confidence interval, 0.31-0.62). These findings suggest that a single measurement is sufficient to characterize the serum prolactin level of postmenopausal women for epidemiological research. For premenopausal women, however, multiple samples are desirable. Controlling for phase of the menstrual cycle does not appear to substantially improve the reliability of premenopausal measurements
— id: 6424, year: 1993, vol: 2, page: 411, stat: Journal Article,

PROSPECTIVE-STUDY OF SERUM PROLACTIN AND BREAST-CANCER
KOENIG, K; TONIOLO, P; BRUNING, P; BONFRER, J; SHORE, R; ZELENIUCHJACQUOTTE, A; PASTERNACK, B
1993 OCT 15 ;138(8):601-601, American journal of epidemiology
— id: 52160, year: 1993, vol: 138, page: 601, stat: Journal Article,

The influence of medical conditions associated with hormones on the risk of breast cancer [published erratum appears in Int J Epidemiol 1994 Dec;23(6):1330]
Moseson M; Koenig KL; Shore RE; Pasternack BS
1993 Dec;22(6):1000-1009, International journal of epidemiology
Medical conditions related to hormonal abnormalities were investigated in a case-control study of breast cancer among women who attended a screening centre. Information was obtained by telephone interview regarding physician-diagnosed medical conditions such as thyroid or liver diseases, diabetes, and hypertension, as well as hirsutism, acne, galactorrhoea, and reproductive, menstrual, and gynaecological factors. Results are presented for 354 cases and 747 controls. Women with fertility problems who never succeeded in becoming pregnant were at significantly increased breast cancer risk (adjusted odds ratio [OR] = 3.5; 95% confidence interval [CI]:1.1-10.9). An elevated cancer risk was also associated with having excess body hair (OR = 1.5; 95% CI:1.0-2.3), or having excess body hair in addition to persistent adult acne (OR = 6.8; 95% CI:1.7-27.1). Recurrent amenorrhea (OR = 3.5; 95% CI:1.1-11.5), and a treated hyperthyroid condition (OR = 2.2; 95% CI:1.1-4.4) were significantly associated with risk. A non-significant elevation of risk was present for endometrial hyperplasia (OR = 1.8; 95% CI: 0.8-4.0). There was a suggestion of an association between a history of galactorrhoea and breast cancer risk (OR = 2.0; 95% CI:0.8-4.9) among premenopausal women. No associations were found with other medical or gynaecological factors. The possibility that some of these findings are due to chance cannot be excluded because of the problem of multiple comparisons
— id: 6464, year: 1993, vol: 22, page: 1000, stat: Journal Article,

PROSPECTIVE-STUDY OF ENDOGENOUS ESTROGENS AND BREAST-CANCER
TONIOLO, P; LEVITZ, M; JACQUOTTE, A; KOENIG, K; SHORE, R; PASTERNACK, B
1993 OCT 15 ;138(8):601-601, American journal of epidemiology
— id: 52159, year: 1993, vol: 138, page: 601, stat: Journal Article,

Age-dependence of responses to acute ozone exposure in rats
Gunnison AF; Weideman PA; Sobo M; Koenig KL; Chen LC
1992 Apr;18(3):360-369, Fundamental & applied toxicology
Previous work from this laboratory demonstrated that neonatal rats and postweanling rabbits are more sensitive to ozone-induced stimulation of pulmonary arachidonic acid (AA) metabolism than are young adults (Fundam. Appl. Toxicol. 15, 779.) In the study reported here, we have extended our initial investigation to include the influence of animal age on temporal aspects of pulmonary AA metabolism and several other responses to brief exposures to 1 ppm ozone. Rats of discrete ages ranging from 13 days to 16 weeks were exposed to 1 ppm ozone or to air for 2, 4, or 6 hr. Immediately following exposure the lungs were lavaged with six consecutive volumes of phosphate-buffered saline and the acellular fluid from the first lavage volume recovered was analyzed for its content of prostaglandin E2 (PGE2), protein, and lactate dehydrogenase. Leukocytes recovered by lavage were quantitated and characterized by viability and percentage of polymorphonuclear (PMN) cells. Several lines of evidence verified that PGE2 was produced by the lung as a consequence of ozone exposure and that its concentration in the fluid from the first lavage was a reasonably good index of pulmonary AA metabolism to prostanoids. We also demonstrated that the lavage process itself stimulates the lung, resulting in increased AA metabolism to prostanoids that were recovered in the second and following lavage volumes. The time course of PGE2 production by the ozone-exposed lung varied considerably with animal age. Neonatal rats 13 days of age were the most sensitive to ozone stimulation. At 2 hr of exposure, PGE2 concentration in the first lung lavage of these animals peaked at values approximately two orders of magnitude above controls and then decreased sharply with continued exposure. Adults and older neonates (18 days of age) were much less responsive to 2-hr exposures; however, continued exposure of these rats for up to 6 hr resulted in increasing PGE2 concentration in the first lung lavage. Other responses showed various degree of age dependence. The percentage of lavaged leukocytes that were nonviable (i.e., trypan blue-positive) showed a strong inverse correlation with animal age. In 13-day-old rats that were exposed for 6 hr, the percentage of dead leukocytes reached nearly 50%. In addition, sheets or clumps of dead cells that were judged to be epithelial cells were lavaged from these animals. Conversely, 16-week-old adult males exposed to ozone for 6 hr showed little evidence of damage to cells of the respiratory tract.(ABSTRACT TRUNCATED AT 400 WORDS)
— id: 13637, year: 1992, vol: 18, page: 360, stat: Journal Article,

Reproducibility of Wolfe's classification of mammographic parenchymal patterns
Toniolo P; Bleich AR; Beinart C; Koenig KL
1992 Jan;21(1):1-7, Preventive medicine
BACKGROUND: Inadequate reproducibility of Wolfe's classification of mammographic parenchymal patterns may explain its limited use in clinical and screening practice. If the misclassification of mammographic parenchymal pattern categories is substantial, inconsistencies in study results will occur, which could at least partially explain the frequent inability to replicate Wolfe's findings in studies of breast cancer. In this article, results of a study to determine whether consensus to resolve inconsistencies between raters would improve the level of concordance in mammographic parenchymal pattern categorization and thus help reduce misclassification are presented. METHODS. One hundred consecutive mammograms from a large screening clinic in New York City were classified independently by two expert mammographers on two separate occasions, 8 days apart. Coding was repeated in two consensus conferences several weeks later. Reliability was estimated by computing intraclass correlation coefficients. RESULTS: Initially, the average intraobserver reliability for the four patterns was 0.68 and the interobserver reliability was 0.65. After consensus, reliability improved markedly to 0.88. CONCLUSION: It is concluded that the added complication and cost of consensus ratings will be more than offset by a substantial increase in precision
— id: 13713, year: 1992, vol: 21, page: 1, stat: Journal Article,

Hair dye use and breast cancer: a case-control study among screening participants
Koenig KL; Pasternack BS; Shore RE; Strax P
1991 May 15;133(10):985-995, American journal of epidemiology
To investigate whether hair dye use increases the risk of breast cancer, a case-control study was conducted among patients attending a screening center in New York City. The study group consisted of 398 breast cancer cases identified at the screening center between 1977 and 1981, and 790 randomly selected controls screened during the same period. Subjects were interviewed by telephone to obtain information on known risk factors for breast cancer, along with a complete history of hair dye use detailing type of dye, color, duration, frequency, and temporal periods of use. Most subjects (77%) had used hair dye at least once, 38% of the subjects at least 100 times. However, little increased risk of breast cancer was found among hair dye users. The adjusted odds ratio for ever having used hair dye was 0.8 (95% confidence interval 0.6-1.1), and there was no evidence of a trend in risk with increasing number of hair dye uses. The results were the same whether all past exposures were considered or only exposures more than 10 years before disease. Breast cancer risk did not increase with increasing intensity of exposure, as measured by frequency of use or darkness of color. No effect was seen for different types or colors of dye, or for use during different periods of reproductive life. Although personal hair dye use was unrelated to breast cancer risk, there was an adjusted odds ratio of 3.0 (95% confidence interval 1.1-7.8) for 5 or more years of work as a beautician. Overall, the results of this study, taken in conjunction with the findings of other epidemiologic studies, do not implicate hair dye use as an important cause of human breast cancer
— id: 8284, year: 1991, vol: 133, page: 985, stat: Journal Article,

RELIABILITY OF SERUM PROLACTIN MEASUREMENTS
KOENIG, KL; TONIOLO, P; BONFRER, JMG; PASTERNACK, BS; SHORE, RE; BRUNING, PF
1991 OCT 1 ;134(7):753-753, American journal of epidemiology
— id: 51536, year: 1991, vol: 134, page: 753, stat: Journal Article,

Endogenous hormones and breast cancer: a prospective cohort study [see comments]
Toniolo PG; Pasternack BS; Shore RE; Sonnenschein E; Koenig KL; Rosenberg C; Strax P; Strax S
1991 May;18 Suppl 1:S23-S26, Breast cancer research & treatment
A cohort study is under way in New York City to evaluate how levels of endogenous reproductive hormones influence the risk of breast cancer. The study, in which approximately 15,000 women are being recruited, utilizes a prospective design in which volunteers are asked to provide repeated specimens of serum during the period 1985-1992. A case-control study nested within the cohort is planned by which specimens from all cases arising in the population and from a randomly selected sample of time-matched controls will be analyzed and compared. As of December 31, 1989, 13,609 volunteers had donated blood specimens, about 50% of whom had already donated more than once. Of the 187 incident breast cancer cases who are expected to arise in the cohort before the end of 1992, 77 have been detected thus far
— id: 6539, year: 1991, vol: 18 Suppl 1, page: S23, stat: Journal Article,

RELIABILITY OF PERCENT ESTRADIOL BINDING TO PROTEINS - IMPLICATIONS FOR STUDY DESIGN
TONIOLO, P; PASTERNACK, B; KOENIG, K; ROSENBERG, C; SHORE, R; BANERJEE, S; LEVITZ, M
1991 OCT 1 ;134(7):774-775, American journal of epidemiology
— id: 51537, year: 1991, vol: 134, page: 774, stat: Journal Article,

Carcinogenic sulfide salts of nickel and cadmium induce H2O2 formation by human polymorphonuclear leukocytes
Zhong ZJ; Troll W; Koenig KL; Frenkel K
1990 Dec 1;50(23):7564-7570, Cancer research
Some derivatives of nickel, cadmium, and cobalt are carcinogenic in humans and/or animals but their mechanisms of action are not known. We show that they are capable of stimulating human polymorphonuclear leukocytes (PMNs), as measured by H2O2 formation, a known tumor promoter. Most effective were the carcinogens nickel subsulfide, which caused a 550% net increase in H2O2 over that formed by resting PMNs, followed by cadmium sulfide, 400%, and nickel disulfide, 200%. Nickel sulfide and cobalt sulfide caused statistically nonsignificant increases of 45 and 20%, respectively. Noncarcinogenic barium and manganese sulfides, and sulfates of nickel, cadmium, and cobalt were inactive. The enhancement of H2O2 formation by CdS and Ni3S2 (1 mumol/2.5 x 10(5) PMNs) was comparable to that mediated by the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate, used at 0.5 and 1 nM, respectively. Concurrent treatment of 12-O-tetradecanoylphorbol-13-acetate-stimulated PMNs with Ni3S2 or NiS caused a decrease in H2O2 accumulation from that expected if the effects were additive. Including catalase in the reaction mixture proved that the oxidant formed by stimulated PMNs was H2O2, whereas adding superoxide dismutase showed that superoxide was also present in PMN samples treated with NiS but not with Ni3S2. Since nickel- and cadmium-containing particulates are deposited in the lungs and cause infiltration of PMNs, the ability to activate those cells and induce H2O2 formation may contribute to their carcinogenicity
— id: 14252, year: 1990, vol: 50, page: 7564, stat: Journal Article,

Hair dye use and breast cancer : a case-control study
Koenig, Karen L
[S.l. : s.n.], 1989,
Thesis (Ph.D.) -- New York University, 1989
— id: 1282, year: 1989, vol: , page: , stat: ,

Hair dye use and breast cancer
Koenig KL; Pasternack BS; Shore RE
1984 Jun;72(6):1211-1212, Journal of the National Cancer Institute
— id: 10282, year: 1984, vol: 72, page: 1211, stat: Journal Article,