Yu Chen, Ph.D., MPH

Health Effect of Arsenic Longitudinal Study-Recent Findings
Ahsan, Habibul; Chen, Yu; Parvez, Faruque; Argos, Maria; Rathouz, Paul; Kibriya, Muhammad; Slavkovich, Vesna; Islam, Tariqul; Hasan, Rabiul; Zaman, Rakib-Uz; Ahmed, Alauddin; van Geen, Lex; Graziano, Joseph
2011 JAN ;22(1):S48-S49, Epidemiology
— id: 124130, year: 2011, vol: 22, page: S48, stat: Journal Article,

Body mass index and diabetes in Asia: a cross-sectional pooled analysis of 900,000 individuals in the Asia cohort consortium
Boffetta, Paolo; McLerran, Dale; Chen, Yu; Inoue, Manami; Sinha, Rashmi; He, Jiang; Gupta, Prakash Chandra; Tsugane, Shoichiro; Irie, Fujiko; Tamakoshi, Akiko; Gao, Yu-Tang; Shu, Xiao-Ou; Wang, Renwei; Tsuji, Ichiro; Kuriyama, Shinichi; Matsuo, Keitaro; Satoh, Hiroshi; Chen, Chien-Jen; Yuan, Jian-Min; Yoo, Keun-Young; Ahsan, Habibul; Pan, Wen-Harn; Gu, Dongfeng; Pednekar, Mangesh Suryakant; Sasazuki, Shizuka; Sairenchi, Toshimi; Yang, Gong; Xiang, Yong-Bing; Nagai, Masato; Tanaka, Hideo; Nishino, Yoshikazu; You, San-Lin; Koh, Woon-Puay; Park, Sue K; Shen, Chen-Yang; Thornquist, Mark; Kang, Daehee; Rolland, Betsy; Feng, Ziding; Zheng, Wei; Potter, John D
2011 ;6(6):e19930-e19930, PLoS ONE
BACKGROUND: The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact have not been adequately studied in Asia. METHODS AND FINDINGS: A pooled cross-sectional analysis was conducted to evaluate the association between baseline body mass index (BMI, measured as weight in kg divided by the square of height in m) and self-reported diabetes status in over 900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan, Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI, after adjustment for potential confounding factors. OR were pooled across cohorts using a random-effects meta-analysis. The sex- and age-adjusted prevalence of diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across participating cohorts. Using the category 22.5-24.9 Kg/m(2) as reference, the OR for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI lower than 15.0 kg/m(2) to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m(2). The positive association between BMI and diabetes prevalence was present in all cohorts and in all subgroups of the study population, although the association was stronger in individuals below age 50 at baseline (p-value of interaction<0.001), in cohorts from India and Bangladesh (p<0.001), in individuals with low education (p-value 0.02), and in smokers (p-value 0.03); no differences were observed by gender, urban residence, or alcohol drinking. CONCLUSIONS: This study estimated the shape and the strength of the association between BMI and prevalence of diabetes in Asian populations and identified patterns of the association by age, country, and other risk factors for diabetes
— id: 135272, year: 2011, vol: 6, page: e19930, stat: Journal Article,

Perceptual Measurement in Schizophrenia: Promising Electrophysiology and Neuroimaging Paradigms From CNTRICS
Butler PD; Chen Y; Ford JM; Geyer MA; Silverstein SM; Green MF
2011 Jan;38(1):81-91, Schizophrenia bulletin
The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging paradigms for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were 'gain control' and 'visual integration.' CNTRICS received 6 task nominations for imaging paradigms for gain control and 3 task nominations for integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group believed that one task (mismatch negativity) was already mature and was being incorporated into multisite clinical trials. The breakout group recommended that 1 visual task (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased stimuli) and 2 auditory measures (an event-related potential (ERP) measure of corollary discharge and a functional magnetic resonance imaging (fMRI) version of prepulse inhibition of startle) be adapted for use in clinical trials in schizophrenia research. For visual integration, the breakout group recommended that fMRI and ERP versions of a contour integration test and an fMRI version of a coherent motion test be adapted for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used in the breakout group to evaluate and recommend tasks for further development
— id: 138503, year: 2011, vol: 38, page: 81, stat: Journal Article,

Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study
Chen Y; Parvez F; Liu M; Pesola GR; Gamble MV; Slavkovich V; Islam T; Ahmed A; Hasan R; Graziano JH; Ahsan H
2011 Jun;40(3):828-835, International journal of epidemiology
BACKGROUND: Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. METHODS: We evaluated the association between As exposure from drinking water and proteinuria in 11 122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. RESULTS: At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (</=7, 8-39, 40-91, 92-179 and 180-864 microg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77-1.27], POR 1.23 (95% CI 0.97-1.57), POR 1.50 (95% CI 1.18-1.89) and POR 1.59 (95% CI 1.26-2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67-1.03) and POR 0.91 (95% CI 0.74-1.12) for participants with a decreasing level of >70 and 17-70 microg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97-1.42) and POR 1.42 (95% CI 1.16-1.73) for participants with an increasing level of 16-68 and >68 microg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As -16 to 15 microg/l). CONCLUSION: The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure
— id: 124140, year: 2011, vol: 40, page: 828, stat: Journal Article,

Molecular interaction and functional regulation of connexin50 gap junctions by calmodulin
Chen Y; Zhou Y; Lin X; Wong HC; Xu Q; Jiang J; Wang S; Lurtz MM; Louis CF; Veenstra RD; Yang JJ
2011 May 1;435(3):711-722, Biochemical journal
Connexin 50 (Cx50), a member of the alpha family of gap junction proteins expressed in the lens of the eye, has been shown to be essential for normal lens development. In the present study, we identified a calmodulin (CaM) binding domain (CaMBD, residues 141-166) in the intracellular loop of Cx50. Elevations in intracellular Ca2+ concentration effected a 95% decline in junctional conductance (gj) of Cx50 in N2A cells that is likely mediated by CaM, because inclusion of the CaM inhibitor, calmidazolium, prevented this Ca2+-dependent decrease in gj. The direct involvement of the Cx50 CaMBD in this Ca2+/CaM-dependent regulation was further demonstrated by inclusion of a synthetic peptide encompassing the CaMBD in both whole cell patch pipettes, which effectively prevented the intracellular Ca2+-dependent decline in gj. Biophysical studies using NMR and fluorescence spectroscopy further reveal that the peptide stoichiometrically binds to Ca2+/CaM with an affinity of ~5 nM. The binding of the peptide expanded the Ca2+ sensing range of CaM by increasing the Ca2+ affinity of the C-lobe of CaM, while decreasing the Ca2+ affinity of the N-lobe of CaM. Overall, these results demonstrate that the binding of Ca2+/CaM to the intracellular loop of Cx50 is critical for mediating the Ca2+-dependent inhibition of Cx50 gap junctions in the lens of the eye
— id: 124158, year: 2011, vol: 435, page: 711, stat: Journal Article,

Farm microbiome and childhood asthma
Chen, Yu; Blaser, Martin J
2011 May 19;364(20):1972-1973, New England journal of medicine
— id: 140485, year: 2011, vol: 364, page: 1972, stat: Journal Article,

Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study
Chen, Yu; Graziano, Joseph H; Parvez, Faruque; Liu, Mengling; Slavkovich, Vesna; Kalra, Tara; Argos, Maria; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; van Geen, Alexander; Ahsan, Habibul
2011 ;342:d2431-d2431, British medical journal. BMJ (International ed.)
OBJECTIVE: To evaluate the association between arsenic exposure and mortality from cardiovascular disease and to assess whether cigarette smoking influences the association. DESIGN: Prospective cohort study with arsenic exposure measured in drinking water from wells and urine. SETTING: General population in Araihazar, Bangladesh. PARTICIPANTS: 11 746 men and women who provided urine samples in 2000 and were followed up for an average of 6.6 years. MAIN OUTCOME MEASURE: Death from cardiovascular disease. RESULTS: 198 people died from diseases of circulatory system, accounting for 43% of total mortality in the population. The mortality rate for cardiovascular disease was 214.3 per 100 000 person years in people drinking water containing <12.0 microg/L arsenic, compared with 271.1 per 100 000 person years in people drinking water with >/=12.0 microg/L arsenic. There was a dose-response relation between exposure to arsenic in well water assessed at baseline and mortality from ischaemic heart disease and other heart disease; the hazard ratios in increasing quarters of arsenic concentration in well water (0.1-12.0, 12.1-62.0, 62.1-148.0, and 148.1-864.0 microg/L) were 1.00 (reference), 1.22 (0.65 to 2.32), 1.35 (0.71 to 2.57), and 1.92 (1.07 to 3.43) (P=0.0019 for trend), respectively, after adjustment for potential confounders including age, sex, smoking status, educational attainment, body mass index (BMI), and changes in urinary arsenic concentration since baseline. Similar associations were observed when baseline total urinary arsenic was used as the exposure variable and for mortality from ischaemic heart disease specifically. The data indicate a significant synergistic interaction between arsenic exposure and cigarette smoking in mortality from ischaemic heart disease and other heart disease. In particular, the hazard ratio for the joint effect of a moderate level of arsenic exposure (middle third of well arsenic concentration 25.3-114.0 microg/L, mean 63.5 microg/L) and cigarette smoking on mortality from heart disease was greater than the sum of the hazard ratios associated with their individual effect (relative excess risk for interaction 1.56, 0.05 to 3.14; P=0.010). CONCLUSIONS: Exposure to arsenic in drinking water is adversely associated with mortality from heart disease, especially among smokers
— id: 132196, year: 2011, vol: 342, page: d2431, stat: Journal Article,

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,

Arsenic exposure and toxicology: a historical perspective
Hughes, Michael F; Beck, Barbara D; Chen, Yu; Lewis, Ari S; Thomas, David J
2011 Oct;123(2):305-332, Toxicological sciences
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve
— id: 139918, year: 2011, vol: 123, page: 305, stat: Journal Article,

A marked deficiency in circulating and renal IGF-I peptide does not inhibit compensatory renal enlargement in uninephrectomized mice
Landau D.; Biada J.; Chen Y.; Sood S.; Yakar S.; LeRoith D.; Segev Y.; Rabkin R.
2011 ;21(5):279-284, Growth hormone & IGF research
Objective: Increase in kidney IGF-I levels due to its increased trapping from the circulation was hypothesized to be a key mediator of compensatory renal enlargement. We tested this hypothesis using genetically engineered mice with extremely low circulating IGF-I levels. Design: Both IGF-I deficient (ID) and normal (N) mice underwent a uninephrectomy (UNx) and sacrificed 2 or 9. days later. Results: Initial body weight (BW) and kidney weight (KW) were significantly reduced in ID vs. N mice, while KW/BW ratios were similar. KW increased post-UNx to a comparable extent in ID and N mice (125 +/- 4 and 118 +/- 6% of pre-UNx KW, p < 0.05 vs. C). Kidney IGF-I mRNA levels were similar in the ID and N mice and did not change post-UNx. Kidney IGF-I peptide levels pre-UNx were significantly lower in ID vs. N mice (25 +/- 5 vs. 305 +/- 39. ng/g) and increased in both groups after UNx, remaining low in ID mice (45 +/- 4 in ID vs 561 +/- 64. ng/g in N). IGF type 1 receptor phosphorylation was unchanged. Conclusion: While a severe deficiency of circulating IGF-I impairs body growth, UNx induces a significant and proportional increase in renal mass in ID mice despite markedly decreased kidney IGF-I levels (> 90% reduction) and no significant change in receptor phosphorylation. This all suggests that factors other than circulating and locally produced IGF-I are responsible for compensatory renal enlargement. 2011 Elsevier Ltd
— id: 137907, year: 2011, vol: 21, page: 279, stat: Journal Article,

Associations of Arsenic Exposure With Impaired Lung Function and Mortality From Diseases of the Respiratory System: Findings From the Health Effects of Arsenic Longitudinal Study (HEALS)
Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Zaman, Rakib-Uz; Ahmed, Alauddin; Islam, Tariqul; Argos, Maria; Hasan, Rabiul; Slavkovich, Vesna; Graziano, Joseph; Ahsan, Habibul
2011 JAN ;22(1):S179-S179, Epidemiology
— id: 124132, year: 2011, vol: 22, page: S179, stat: Journal Article,

Association Between Oral Health And Gastric Precancerous Lesions
Salazar CR; Francois F; Li Y; Corby P; Hays R; Leung C; Bedi S; Segers S; Queiroz E; Sun J; Wang B; Ho H; Craig R; Cruz G; Blaser MJ; Perez-Perez G; Hayes RB; Dasanayake A; Pei Z; Chen Y
2011 Dec 1;:399-403 #, Carcinogenesis
Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared to non-cases, cases were significantly more likely to not floss their teeth (Odds Ratio [OR] = 2.89, 95% Confidence Interval [CI]: 1.09-7.64), adjusting for age, sex, race, BMI, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n=28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases (OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites [equivalent to 19.7%]), independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions
— id: 147670, year: 2011, vol: , page: 399, stat: Journal Article,

Fast CT image processing using parallelized non-local means
Wu H.; Zhang W.; Gao D.; Yin X.; Chen Y.; Wang W.
2011 ;31(6):437-441, Journal of medical & biological engineering = Zhonghua yi xue gong cheng xue kan
Reducing the radiation dose delivered to patients has been an important concern since the introduction of X-ray computed tomography (CT). However, low-dose CT images tend to be severely degraded by noise. This paper proposes using parallelized non-local means (PNM) under a computation framework for improving low-dose X-ray CT images. For the proposed PNM method, the pixel intensities are processed based on the self-similarity properties of tissues with various levels of attenuation across large-scale neighborhoods. In the experiment, CT images from a Siemens CT scanner with 16 detector rows are collected for various dose levels. Results on both phantom and clinical CT images from various human parts validate the performance of the proposed accelerated parallel approach in terms of noise and artifact suppression and feature preservation
— id: 142056, year: 2011, vol: 31, page: 437, stat: Journal Article,

Association between body-mass index and risk of death in more than 1 million Asians
Zheng, Wei; McLerran, Dale F; Rolland, Betsy; Zhang, Xianglan; Inoue, Manami; Matsuo, Keitaro; He, Jiang; Gupta, Prakash Chandra; Ramadas, Kunnambath; Tsugane, Shoichiro; Irie, Fujiko; Tamakoshi, Akiko; Gao, Yu-Tang; Wang, Renwei; Shu, Xiao-Ou; Tsuji, Ichiro; Kuriyama, Shinichi; Tanaka, Hideo; Satoh, Hiroshi; Chen, Chien-Jen; Yuan, Jian-Min; Yoo, Keun-Young; Ahsan, Habibul; Pan, Wen-Harn; Gu, Dongfeng; Pednekar, Mangesh Suryakant; Sauvaget, Catherine; Sasazuki, Shizuka; Sairenchi, Toshimi; Yang, Gong; Xiang, Yong-Bing; Nagai, Masato; Suzuki, Takeshi; Nishino, Yoshikazu; You, San-Lin; Koh, Woon-Puay; Park, Sue K; Chen, Yu; Shen, Chen-Yang; Thornquist, Mark; Feng, Ziding; Kang, Daehee; Boffetta, Paolo; Potter, John D
2011 Feb 24;364(8):719-729, New England journal of medicine
BACKGROUND: Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS: We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS: In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS: Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis
— id: 131923, year: 2011, vol: 364, page: 719, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Abnet, Christian C; Chen, Yu; Chow, Wong-Ho; Gao, Yu-Tang; Helzlsouer, Kathy J; Le Marchand, Loic; McCullough, Marjorie L; Shikany, James M; Virtamo, Jarmo; Weinstein, Stephanie J; Xiang, Yong-Bing; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Arslan, Alan A; Campbell, David S; Campbell, Peter T; Hayes, Richard B; Horst, Ronald L; Kolonel, Laurence N; Nomura, Abraham M Y; Purdue, Mark P; Snyder, Kirk; Shu, Xiao-Ou
2010 Jul 1;172(1):94-106, American journal of epidemiology
Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers
— id: 114065, year: 2010, vol: 172, page: 94, stat: Journal Article,

Dietary B vitamin intakes and urinary total arsenic concentration in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh
Argos, Maria; Rathouz, Paul J; Pierce, Brandon L; Kalra, Tara; Parvez, Faruque; Slavkovich, Vesna; Ahmed, Alauddin; Chen, Yu; Ahsan, Habibul
2010 Dec;49(8):473-481, European journal of nutrition
PURPOSE: The objective of this analysis was to evaluate the effects of dietary B vitamin intakes on creatinine-adjusted urinary total arsenic concentration among individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Araihazar, Bangladesh. Arsenic exposure is a major public health problem in Bangladesh, where nearly 77 million people have been chronically exposed to arsenic through the consumption of naturally contaminated groundwater. Dietary factors influencing the metabolism of ingested arsenic may potentially be important modifiers of the health effects of arsenic in this population. METHODS: Daily average B vitamin intakes from a validated food frequency questionnaire and laboratory data on drinking water and urinary arsenic concentrations among 9,833 HEALS cohort participants were utilized. Statistical analyses were conducted using generalized estimating equations incorporating knotted spline linear regression. RESULTS: Increasing dietary intakes of thiamin, niacin, pantothenic acid, and pyridoxine were found to significantly increase urinary total arsenic excretion, adjusted for daily arsenic intake from drinking water and other potential confounders. CONCLUSIONS: These results suggest that higher intakes of certain B vitamins may enhance the excretion of arsenic from the body. This study offers new insights into modifiable dietary factors that relate to arsenic excretion and thus provides potential avenues for the prevention of arsenic-related health effects
— id: 138177, year: 2010, vol: 49, page: 473, stat: Journal Article,

No association between arsenic exposure from drinking water and diabetes mellitus: a cross-sectional study in Bangladesh
Chen, Yu; Ahsan, Habibul; Slavkovich, Vesna; Peltier, Gretchen Loeffler; Gluskin, Rebecca T; Parvez, Faruque; Liu, Xinhua; Graziano, Joseph H
2010 Sep;118(9):1299-1305, Environmental health perspectives
BACKGROUND: The long-term effects of arsenic exposure from drinking water at levels < 300 microg/L and the risk of diabetes mellitus remains a controversial topic. METHOD: We conducted a population-based cross-sectional study using baseline data from 11,319 participants in the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, to evaluate the associations of well water arsenic and total urinary arsenic concentration and the prevalence of diabetes mellitus and glucosuria. We also assessed the concentrations of well water arsenic, total urinary arsenic, and urinary arsenic metabolites in relation to blood glycosylated hemoglobin (HbA1c) levels in subsets of the study population. RESULTS: More than 90% of the cohort members were exposed to drinking water with arsenic concentration < 300 microg/L. We found no association between arsenic exposure and the prevalence of diabetes. The adjusted odds ratios for diabetes were 1.00 (referent), 1.35 [95% confidence interval (CI), 0.90-2.02], 1.24 (0.82-1.87), 0.96 (0.62-1.49), and 1.11 (0.73-1.69) in relation to quintiles of time-weighted water arsenic concentrations of 0.1-8, 8-41, 41-91, 92-176, and > or = 177 microg/L, respectively, and 1.00 (referent), 1.29 (0.87-1.91), 1.05 (0.69-1.59), 0.94 (0.61-1.44), and 0.93 (0.59-1.45) in relation to quintiles of urinary arsenic concentrations of 1-36, 37-66, 67-114, 115-204, and > or = 205 microg/L, respectively. We observed no association between arsenic exposure and prevalence of glucosuria and no evidence of an association between well water arsenic, total urinary arsenic, or the composition of urinary arsenic metabolites and HbA1c level. CONCLUSIONS: Our findings do not support an association of arsenic exposure from drinking water and a significantly increased risk of diabetes mellitus in the range of levels observed. Further prospective studies would be valuable in confirming the findings
— id: 125499, year: 2010, vol: 118, page: 1299, stat: Journal Article,

Determinants of oral health care utilization among diverse groups of immigrants in New York City
Cruz, Gustavo D; Chen, Yu; Salazar, Christian R; Karloopia, Rajiv; LeGeros, Racquel Z
2010 Jul;141(7):871-878, Journal of the American Dental Association
BACKGROUND: Few studies have examined utilization of oral health care services among immigrants. The authors examined the determinants of utilization of oral health care among a diverse group of immigrants in New York City. METHODS: The authors examined and interviewed 1,417 foreign-born people, aged 18 to 65 years, who were residents of New York City. They conducted examinations by using criteria established by the National Institute of Dental and Craniofacial Research, Bethesda, Md. The authors used unconditional logistic regression to estimate odds ratios (ORs) and 95 percent confidence intervals for having visited a dentist within the previous year for each of the independent variables. RESULTS: More than 70 percent of the participants lacked dental insurance and only about 31 percent reported that they had visited a dentist within the previous year. Flossing (OR = 1.18), dental insurance (OR = 1.58), having a regular source of dental care (OR = 4.76) and more filled teeth (1.33) were independent predictors of utilization of services. CONCLUSIONS: Having a regular source of dental care and having dental insurance are important predictors of immigrants' utilization of oral health care services in New York City. CLINICAL IMPLICATIONS: The study results suggest the importance of establishing affordable, culturally appropriate, community-based oral health care services to improve the oral health of vulnerable populations
— id: 146528, year: 2010, vol: 141, page: 871, 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,

Quantitation of major human cutaneous bacterial and fungal populations
Gao, Zhan; Perez-Perez, Guillermo I; Chen, Yu; Blaser, Martin J
2010 Oct;48(10):3575-3581, Journal of clinical microbiology
Because the human skin microbiota may play roles in the causation or modification of skin diseases, we sought to provide initial quantitative analysis from different cutaneous locations. We developed quantitative PCRs to enumerate the total bacterial and fungal populations, as well as the most common bacterial and fungal genera present in six locales, in eight healthy subjects. We used a set of primers and TaqMan MGB probes based on the bacterial 16S rRNA and fungal internally transcribed spacer region, as well as bacterial genus-specific probes for Propionibacterium, Corynebacterium, Streptococcus, and Staphylococcus and a fungal genus-specific probe for Malassezia. The extent of human DNA contamination of the specimen was determined by quantitating the human housekeeping GAPDH gene. The highest level of 16S rRNA copies of bacteria was present in the axilla (4.44 +/- 0.18 log(10) copies/mul [mean +/- standard error of the mean]), with normalization based on GAPDH levels, but the other five locations were similar to one another (range, 2.48 to 2.89 log(10) copies/mul). There was strong symmetry between the left and right sides. The four bacterial genera accounted for 31% to 59% of total bacteria, with the highest percent composition in the axilla and the lowest in the forearm. Streptococcus was the most common genus present on the forehead and behind the ear. Corynebacterium spp. were predominant in the axilla. Fungal levels were 1 to 2 log(10) lower than for bacteria, with Malassezia spp. accounting for the majority of fungal gene copies. These results provide the first quantitation of the site and host specificities of major bacterial and fungal populations in human skin and present simple methods for their assessment in studies of disease
— id: 114044, year: 2010, vol: 48, page: 3575, stat: Journal Article,

Protein and amino acid intakes in a rural area of Bangladesh
Heck, Julia E; Nieves, Jeri W; Chen, Yu; Parvez, Faruque; Brandt-Rauf, Paul W; Howe, Geoffrey R; Ahsan, Habibul
2010 Jun;31(2):206-213, Food & nutrition bulletin
BACKGROUND: Few studies have described protein and amino acid intakes in rural Bangladesh, a country with considerable undernutrition. OBJECTIVE: The purpose of this population-based study was to assess and describe protein and amino acid intakes in Araihazar, Bangladesh. METHODS: The study participants were 11,170 adult men and women who participated in the Health Effects of Arsenic Longitudinal Study (HEALS), which had a 98% participation rate. Dietary exposures were assessed by a food-frequency questionnaire that had been designed and validated for the HEALS study population. RESULTS: The mean body mass index (BMI) was 19.7 among all participants, and 34.9% of women and 44.4% of men had a BMI below 18.5. The average caloric intake was 2142 and 2394 kcal/day among women and men, respectively, and the mean protein intake was 67.5 and 78.2 g/day. The largest sources of protein were from rice and fish. Greater protein intake was related to younger age and several socioeconomic measures, including more years of education, land and television ownership, and employment in business, farming, or as a laborer (for men) or as a homemaker (for women). CONCLUSIONS: This study found a high prevalence of underweight among study participants. Nonetheless, most participants had adequate protein intake according to Food and Agriculture Organization standards for body weight
— id: 132234, year: 2010, vol: 31, page: 206, 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,

A prospective study of respiratory symptoms associated with chronic arsenic exposure in Bangladesh: findings from the Health Effects of Arsenic Longitudinal Study (HEALS)
Parvez, Faruque; Chen, Yu; Brandt-Rauf, Paul W; Slavkovich, Vesna; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Hassan, Rabiul; Yunus, Mahbub; Haque, Syed E; Balac, Olgica; Graziano, Joseph H; Ahsan, Habibul
2010 Jun;65(6):528-533, Thorax
Background and aims A prospective cohort study was conducted to evaluate the effect of arsenic (As) exposure from drinking water on respiratory symptoms using data from the Health Effects of Arsenic Exposure Longitudinal Study (HEALS), a large prospective cohort study established in Ariahazar, Bangladesh in 2000-2002. A total of 7.31, 9.95 and 2.03% of the 11 746 participants completing 4 years of active follow-up reported having a chronic cough, breathing problem or blood in their sputum, respectively, as assessed by trained physicians. Methods Cox regression models were used to estimate HRs for respiratory symptoms during the follow-up period in relation to levels of chronic As exposure assessed at baseline, adjusting for age, gender, smoking, body mass index, education and arsenic-related skin lesion status. Results Significant positive associations were found between As exposure and respiratory symptoms. As compared with those with the lowest quintile of water As level (</=7 mug/l), the HRs for having respiratory symptoms were 1.27 (95% CI 1.09 to 1.48), 1.39 (95% CI 1.19 to 1.63), 1.43 (95% CI 1.23 to 1.68) and 1.43 (95% CI 1.22 to 1.68) for the second to fifth quintiles of baseline water As concentrations (7-40, 40-90, 90-178 and >178 mug/l), respectively. Similarly, the corresponding HRs in relation to the second to fifth quintiles of urinary arsenic were 1.10 (95% CI 0.94 to 1.27), 1.11 (95% CI 0.95 to 1.29), 1.29 (95% CI 1.11 to 1.49) and 1.35 (95% CI 1.16 to 1.56), respectively. These associations did not differ appreciably by cigarette smoking status. Conclusions This prospective cohort study found a dose-response relationship between As exposure and clinical symptoms of respiratory diseases in Bangladesh. In particular, these adverse respiratory effects of As were clearly evident in the low to moderate dose range, suggesting that a large proportion of the country's population may be at risk of developing serious lung diseases in the future
— id: 109860, year: 2010, vol: 65, page: 528, stat: Journal Article,

A prospective study of body mass index and mortality in Bangladesh
Pierce, Brandon L; Kalra, Tara; Argos, Maria; Parvez, Faruque; Chen, Yu; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Rakibuz-Zaman, Muhammad; Graziano, Joseph; Rathouz, Paul J; Ahsan, Habibul
2010 Aug;39(4):1037-1045, International journal of epidemiology
BACKGROUND: Body mass index (BMI) (kg/m(2)) has a U- or J-shaped relationship with all-cause mortality in Western and East Asian populations. However, this relationship is not well characterized in Bangladesh, where the BMI distribution is shifted towards lower values. METHODS: Using data on 11,445 individuals (aged 18-75 years) participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, we prospectively examined associations of BMI (measured at baseline) with all-cause mortality during approximately 6 years of follow-up. We also examined this relationship within strata of key covariates (sex, age, smoking, education and arsenic exposure). Cox proportional hazards models adjusted for these covariates and BMI-related illnesses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for BMI categories defined by the World Health Organization. RESULTS: Low BMI was strongly associated with increased mortality in this cohort (P-trend < 0.0001). Severe underweight (BMI < 16 kg/m(2); HR 2.06, CI 1.53-2.77) and moderate underweight (16.0-16.9 kg/m(2); HR 1.39, CI 1.01-2.90) were associated with increased all-cause mortality compared with normal BMI (18.6-22.9 kg/m(2)). The highest BMI category (> or =23.0 kg/m(2)) did not show a clear association with mortality (HR 1.10, CI 0.77-1.53). The BMI-mortality association was stronger among individuals with <5 years of formal education (interaction P = 0.02). CONCLUSIONS: Underweight (presumably due to malnutrition) is a major determinant of mortality in the rural Bangladeshi population
— id: 138353, year: 2010, vol: 39, page: 1037, 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,

Reply to raj et Al
Chen, Yu; Blaser, Martin J
2009 Mar 15;199(6):915-916, Journal of infectious diseases
— id: 95157, year: 2009, vol: 199, page: 915, stat: Journal Article,

Arsenic Exposure at Low-to-Moderate Levels and Skin Lesions, Arsenic Metabolism, Neurological Functions, and Biomarkers for Respiratory and Cardiovascular Diseases: Review of Recent Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh
Chen, Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H; Ahsan, Habibul
2009 Sep 1;239(2):184-192, Toxicology & applied pharmacology
The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (>300 mug/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 mug/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 mug/L, mean 99 mug/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention
— id: 99201, year: 2009, vol: 239, page: 184, stat: Journal Article,

The Association of Immigration and Acculturation Attributes With Oral Health Among Immigrants in New York City
Cruz, Gustavo D; Chen, Yu; Salazar, Christian R; Le Geros, Racquel Z
2009 Oct;99 Suppl 2:S474-S480, American journal of public health. AJPH
Objectives. We examined associations between immigration and acculturation attributes and oral disease among immigrants. Methods. We conducted a large cross-sectional study of 1318 immigrants in New York City. We performed comprehensive interviews and oral examinations of the participants and used linear regression models to assess differences in oral disease levels among immigrant subgroups. We also constructed proportional odds models to evaluate the association of oral disease level with length of stay in the United States, age at immigration, and language preference. Results. After we controlled for most known risk factors, country of birth and age at immigration were associated with variations in oral disease prevalence and need for oral health care. Length of stay was inversely associated with need for treatment of dental caries but not with any other indicator of oral disease. Language preference was not associated with any indicator of oral disease. Conclusions. Immigrants' country of birth, length of stay in the United States, and age at immigration played important roles in their oral disease, independently of most known risk factors for oral disease. Our findings emphasize the need for more studies to elucidate the complex relationships of ethnicity, socioeconomic status, and culturally influenced factors that impact immigrants' oral health
— id: 99202, year: 2009, vol: 99 Suppl 2, page: S474, stat: Journal Article,

Dietary intake of methionine, cysteine, and protein and urinary arsenic excretion in Bangladesh
Heck, Julia E; Nieves, Jeri W; Chen, Yu; Parvez, Faruque; Brandt-Rauf, Paul W; Graziano, Joseph H; Slavkovich, Vesna; Howe, Geoffrey R; Ahsan, Habibul
2009 Jan;117(1):99-104, Environmental health perspectives
BACKGROUND: In Bangladesh, millions of people are exposed to arsenic in drinking water; arsenic is associated with increased risk of cancer. Once ingested, arsenic is metabolized via methylation and excreted in urine. Knowledge about nutritional factors affecting individual variation in methylation is limited. OBJECTIVES: The purpose of this study was to examine associations between intakes of protein, methionine, and cysteine total urinary arsenic in a large population-based sample. METHODS: The study subjects were 10,402 disease-free residents of Araihazar, Bangladesh, who participated in the Health Effects of Arsenic Longitudinal Study (HEALS). Food intakes were assessed using a validated food frequency questionnaire developed for the study population. Nutrient composition was determined by using the U.S. Department of Agriculture National Nutrient Database for Standard Reference. Generalized estimating equations were used to examine association between total urinary arsenic across quintiles of nutrient intakes while controlling for arsenic exposure from drinking water and other predictors of urinary arsenic. RESULTS: Greater intakes of protein, methionine, and cysteine were associated with 10-15% greater total urinary arsenic excretion, after controlling for total energy intake, body weight, sex, age, tobacco use, and intake of some other nutrients. CONCLUSIONS: Given previously reported risks between lower rates of arsenic excretion and increased rates of cancer, these findings support the role of nutrition in preventing arsenic-related disease
— id: 92587, year: 2009, vol: 117, page: 99, stat: Journal Article,

A Prospective Study of Arsenic Induced Respiratory Symptoms and Chronic Obstructive Pulmonary Disease (COPD): Findings from Health Effects of Arsenic Exposure Longitudinal Study (HEALS) in Bangladesh
Parvez, F; Chen, Y; Yunus, M; Argos, M; Slavkovich, V; Islam, T; Balac, O; Brandt-Rauf, P; Graziano, J; Ahsan, H
2009 NOV ;20(6):S82-S83, Epidemiology
— id: 106447, year: 2009, vol: 20, page: S82, stat: Journal Article,

Extent of Biomass Exposures and Health Effects Among Rural Women in Bangladesh
Parvez, F; Santella, R; Chillrud, S; Chen, Y; Ahmed, A; Hasan, K; Kinney, P; Ahsan, H
2009 NOV ;20(6):S92-S92, Epidemiology
— id: 106448, year: 2009, vol: 20, page: S92, stat: Journal Article,

Arsenic and Cardiovascular Disease
States, J Christopher; Srivastava, Sanjay; Chen, Yu; Barchowsky, Aaron
2009 Feb;107(2):312-323, Toxicological sciences
Chronic arsenic exposure is a world wide health problem. Although arsenic induced cancer has been widely studied, comparatively little attention has been paid to arsenic induced vascular disease. Epidemiological studies have shown that chronic arsenic exposure is associated with increased morbidity and mortality from cardiovascular disease. In addition, studies suggest that susceptibility to arsenic induced vascular disease may be modified by nutritional factors in addition to genetic factors. Recently, animal models for arsenic induced atherosclerosis and liver sinusoidal endothelial cell dysfunction have been developed. Initial studies in these models show that arsenic exposure accelerates and exacerbates atherosclerosis in ApoE-knockout mice. Microarray studies of liver mRNA and micoRNA abundance in mice exposed in utero suggest that a permanent state of stress is induced by the arsenic exposure. Furthermore, the livers of the arsenic exposed mice have activated pathways involved in immune responses suggesting a pro-hyperinflammatory state. Arsenic exposure of mice after weaning show a clear dose response in the extent of disease exacerbation. In addition, increased inflammation in arterial wall is evident. In response to arsenic stimulated oxidative signaling, liver sinusoidal endothelium differentiates into a continuous endothelium that limits nutrient exchange and waste elimination. Data suggest that NADPH oxidase derived superoxide or its derivatives are essential second messengers in the signaling pathway for arsenic-stimulated vessel remodeling. The recent findings provide future directions for research into the cardiovascular effects of arsenic exposure
— id: 90755, year: 2009, vol: 107, page: 312, stat: Journal Article,

Does Helicobacter pylori protect against asthma and allergy?
Blaser, Martin J; Chen, Yu; Reibman, Joan
2008 May;57(5):561-567, Gut: journal of the British Society of Gastroenterology
The microbes that persistently colonize their vertebrate hosts are not accidental (1). Although highly numerous and diverse, there is specificity by site and substantial conservation between individuals. The genus Helicobacter includes spiral, highly motile, urease-positive, gram-negative bacteria that colonize the stomach in many mammals. Each mammal has one or more dominant Helicobacter species and they are highly, if not exclusively, host species-specific (2). Such observations are consistent with the hypothesis that when ancestral mammals diverged from reptiles about 150 million years ago, they contained ancestral helicobacters, which then diverged as their hosts changed. According to this hypothesis, helicobacters represent ancestral biota (flora) in the mammalian stomach. The human-adapted strain is H. pylori (3), which has not been reproducibly observed in any animals other than humans and other primates (3)
— id: 76054, year: 2008, vol: 57, page: 561, stat: Journal Article,

Helicobacter pylori Colonization Is Inversely Associated with Childhood Asthma
Chen, Yu; Blaser, Martin J
2008 Aug 15;198(4):553-560, Journal of infectious diseases
Background. @nbsp; Asthma, a serious health problem worldwide, is becoming more common. Colonization with Helicobacter pylori, a major human indigenous (commensal) microbe, during early life may be relevant to the risk of childhood asthma. Methods. @nbsp; We conducted cross-sectional analyses, using data from 7412 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2000, to assess the association between H. pylori and childhood asthma. Results. @nbsp; H. pylori seropositivity was inversely associated with onset of asthma before 5 years of age and current asthma in children aged 3-13 years. Among participants 3-19 years of age, the presence of H. pylori was inversely related to ever having had asthma (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.45-1.06), and the inverse association with onset of asthma before 5 years of age was stronger (OR, 0.58; 95% CI, 0.38-0.88). Among participants 3-13 years of age, H. pylori positivity was significantly inversely associated with current asthma (OR, 0.41; 95% CI, 0.24-0.69). H. pylori seropositivity also was inversely related to recent wheezing, allergic rhinitis, and dermatitis, eczema, or rash. Conclusions. @nbsp; This study is the first to report an inverse association between H. pylori seropositivity and asthma in children. The findings indicate new directions for research and asthma prevention
— id: 80354, year: 2008, vol: 198, page: 553, stat: Journal Article,

Estrogen-biosynthesis Gene CYP17 and Its Interactions with Reproductive, Hormonal and Lifestyle Factors in Breast Cancer Risk: Results from the Long Island Breast Cancer Study Project
Chen, Yu; Gammon, Marilie D; Teitelbaum, Susan L; Britton, Julie A; Terry, Mary Beth; Shantakumar, Sumitra; Eng, Sybil M; Wang, Qiao; Gurvich, Irina; Neugut, Alfred I; Santella, Regina M; Ahsan, Habibul
2008 Apr;29(4):766-771, Carcinogenesis
The genes that are involved in estrogen biosynthesis, cellular binding, and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T->C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index and the variant C allele was associated with an increased the risk of breast cancer (OR, 1.60; 95% CI, 1.15-2.22). The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (> 51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of post-menopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high body mass index in postmenopausal women
— id: 76055, year: 2008, vol: 29, page: 766, stat: Journal Article,

Do Placental Genes Affect Maternal Breast Cancer? Association between Offspring's CGB5 and CSH1 Gene Variants and Maternal Breast Cancer Risk
Chen, Yu; Kibriya, Muhammad G; Jasmine, Farzana; Santella, Regina M; Senie, Ruby T; Ahsan, Habibul
2008 Dec 1;68(23):9729-9734, Cancer research
The protective effect of full-term pregnancy against breast cancer is thought to be induced by two placental hormones: human chorionic gonadotropin and human chorionic somatotropin hormone (CSH) produced by the placental trophoblastic cells. We hypothesized that variants in placental genes encoding these hormones may alter maternal breast cancer risk subsequent to pregnancy. We conducted a case-control study to examine the association between polymorphisms in a woman's placental (i.e., her offspring's) homologous chorionic gonadotrophin beta5 (CGB5) and CSH1 genes and her post-pregnancy breast cancer risk. A total of 293 breast cancer cases and 240 controls with at least one offspring with available DNA were selected from the New York site of the Breast Cancer Family Registry. Three single nucleotide polymorphisms (SNP) in CGB5 and CSH1 genes were genotyped for 844 offspring of the cases and controls. Overall, maternal breast cancer risk did not significantly differ by the offspring's carrier status of the three SNPs. Among women with an earlier age at childbirth (younger than the median age of 26 years), those with a child carrying the variant C allele of CGB5 rs726002 SNP had an elevated breast cancer risk [odds ratio (OR), 2.09; 95% confidence interval (95% CI), 1.17-3.73]. Among women with a later age at childbirth, breast cancer risk did not differ by offspring's carrier status of CGB5 rs726002 SNP (OR, 0.90; 95% CI, 0.53-1.51; P for interaction = 0.04). The findings suggest that placental CGB5 genotype may be predictive of maternal post-pregnancy breast cancer risk among women who give birth early in life. [Cancer Res 2008;68(23):9729-34]
— id: 90756, year: 2008, vol: 68, page: 9729, stat: Journal Article,

Arsenic exposure and anemia in Bangladesh: a population-based study
Heck, Julia E; Chen, Yu; Grann, Victor R; Slavkovich, Vesna; Parvez, Faruque; Ahsan, Habibul
2008 Jan;50(1):80-87, Journal of occupational & environmental medicine
OBJECTIVE: The purpose of this study was to examine the association between arsenic exposure and anemia, based on blood hemoglobin concentration. METHODS: Hemoglobin measures, skin lesions, arsenic exposure, and nutritional and demographic information were collected from 1954 Bangladeshi participants in the Health Effects of Arsenic Longitudinal Study. We used general linear modeling to assess the association between arsenic exposure and hemoglobin concentration, examining men and women separately. RESULTS: Arsenic exposure (urinary arsenic >200 microg/L) was negatively associated with hemoglobin among all men and among women with hemoglobin <10 d/L. Other predictors of anemia in men and women included older age, lower body mass index, and low intake of iron. Among women, the use of contraceptives predicted higher hemoglobin. CONCLUSIONS: The study suggests an association between high arsenic exposure and anemia in Bangladesh
— id: 132235, year: 2008, vol: 50, page: 80, stat: Journal Article,

Nonmalignant respiratory effects of chronic arsenic exposure from drinking water among never-smokers in Bangladesh
Parvez, Faruque; Chen, Yu; Brandt-Rauf, Paul W; Bernard, Alfred; Dumont, Xavier; Slavkovich, Vesna; Argos, Maria; D'Armiento, Jeanine; Foronjy, Robert; Hasan, M Rashidul; Eunus, H E M Mahbubul; Graziano, Joseph H; Ahsan, Habibul
2008 Feb;116(2):190-195, Environmental health perspectives
BACKGROUND: Arsenic from drinking water has been associated with malignant and nonmalignant respiratory illnesses. The association with nonmalignant respiratory illnesses has not been well established because the assessments of respiratory symptoms may be influenced by recall bias or interviewer bias because participants had visible skin lesions. OBJECTIVES: We examined the relationship of the serum level of Clara cell protein CC16--a novel biomarker for respiratory illnesses--with well As, total urinary As, and urinary As methylation indices. METHODS: We conducted a cross-sectional study in nonsmoking individuals (n = 241) selected from a large cohort with a wide range of As exposure (0.1-761 microg/L) from drinking water in Bangladesh. Total urinary As, urinary As metabolites, and serum CC16 were measured in urine and serum samples collected at baseline of the parent cohort study. RESULTS: We observed an inverse association between urinary As and serum CC16 among persons with skin lesions (beta = -0.13, p = 0.01). We also observed a positive association between secondary methylation index in urinary As and CC16 levels (beta = 0.12, p = 0.05) in the overall study population; the association was stronger among people without skin lesions (beta = 0.18, p = 0.04), indicating that increased methylation capability may be protective against As-induced respiratory damage. In a subsample of study participants undergoing spirometric measures (n = 31), we observed inverse associations between urinary As and predictive FEV(1) (forced expiratory volume measured in 1 sec) (r = -0.37; FEV(1)/forced vital capacity ratio and primary methylation index (r = -0.42, p = 0.01). CONCLUSIONS: The findings suggest that serum CC16 may be a useful biomarker of epithelial lung damage in individuals with arsenical skin lesions. Also, we observed the deleterious respiratory effects of As exposure at concentrations lower than reported in earlier studies
— id: 102606, year: 2008, vol: 116, page: 190, stat: Journal Article,

A CYP19 (aromatase) polymorphism is associated with increased premenopausal breast cancer risk
Talbott, Kathryn E; Gammon, Marilie D; Kibriya, Muhammad G; Chen, Yu; Teitelbaum, Susan L; Long, Chang-Min; Gurvich, Irina; Santella, Regina M; Ahsan, Habibul
2008 Oct;111(3):481-487, Breast cancer research & treatment
Due to the established association between estrogen levels and breast cancer risk, polymorphic variation in genes regulating estrogen levels is thought to be related to breast cancer risk. Aromatase, the protein product of the CYP19 gene, is involved in the production of endogenous estrogens via androgen conversion. We examined whether polymorphic variation in CYP19 associated with increased breast cancer risk in a population based case-control study. We examined two single nucleotide polymorphisms (SNP), rs1008805 (A/G) and rs730154 (C/T), which have been shown to tag SNPs within two different haplotype blocks in CYP19. Among premenopausal women, the presence of at least one G allele at rs1008805 was significantly associated with an increase in the risk of breast cancer (OR = 1.72 [95% CI, 1.20-2.49]), especially with estrogen and progesterone receptor negative breast cancer (OR = 3.89 [1.74-8.70] and OR = 2.52 [1.26-5.05], respectively). No association was observed among postmenopausal women (OR = 1.06 [0.82-1.36]). There was no significant association between rs730154 and breast cancer, regardless of menopausal status. Our results suggest that premenopausal women carrying the G allele at CYP19 rs1008805 have increased risk of breast cancer. The finding supports the potential role of variation in estrogen biosynthesis genes in premenopausal breast cancer risk
— id: 74782, year: 2008, vol: 111, page: 481, stat: Journal Article,

Protective effects of B vitamins and antioxidants on the risk of arsenic-related skin lesions in Bangladesh
Zablotska, Lydia B; Chen, Yu; Graziano, Joseph H; Parvez, Faruque; van Geen, Alexander; Howe, Geoffrey R; Ahsan, Habibul
2008 Aug;116(8):1056-1062, Environmental health perspectives
BACKGROUND: An estimated 25-40 million of the 127 million people of Bangladesh have been exposed to high levels of naturally occurring arsenic from drinking groundwater. The mitigating effects of diet on arsenic-related premalignant skin lesions are largely unknown. OBJECTIVES: The purpose of this study was to clarify the effects of the vitamin B group (thiamin, riboflavin, niacin, pyridoxine, and cobalamin) and antioxidants (vitamins A, C, and E) on arsenic-related skin lesions. METHODS: We performed a cross-sectional study using baseline data from the Health Effects of Arsenic Longitudinal Study (HEALS), 2000-2002, with individual-level, time-weighted measures of arsenic exposure from drinking water. A total of 14,828 individuals meeting a set of eligibility criteria were identified among 65,876 users of all 5,996 tube wells in the 25-km(2) area of Araihazar, Bangladesh; 11,746 were recruited into the study. This analysis is based on 10,628 subjects (90.5%) with nonmissing dietary data. Skin lesions were identified according to a structured clinical protocol during screening and confirmed with further clinical review. RESULTS: Riboflavin, pyridoxine, folic acid, and vitamins A, C, and E significantly modified risk of arsenic-related skin lesions. The deleterious effect of ingested arsenic, at a given exposure level, was significantly reduced (ranging from 46% reduction for pyridoxine to 68% for vitamin C) for persons in the highest quintiles of vitamin intake. CONCLUSIONS: Intakes of B-vitamins and antioxidants, at doses greater than the current recommended daily amounts for the country, may reduce the risk of arsenic-related skin lesions in Bangladesh
— id: 90754, year: 2008, vol: 116, page: 1056, stat: Journal Article,

Arsenic metabolism, genetic susceptibility, and risk of premalignant skin lesions in bangladesh
Ahsan, Habibul; Chen, Yu; Kibriya, Muhammad G; Slavkovich, Vesna; Parvez, Faruque; Jasmine, Farzana; Gamble, Mary V; Graziano, Joseph H
2007 Jun;16(6):1270-1278, Cancer epidemiology biomarkers & prevention
We conducted a case-control study to investigate interindividual variability in susceptibility to health effects of inorganic arsenic due to arsenic metabolism efficiency, genetic factors, and their interaction. A total of 594 cases of arsenic-induced skin lesions and 1,041 controls was selected from baseline participants in a large prospective cohort study in Bangladesh. Adjusted odds ratios (OR) for skin lesions were estimated in relation to the polymorphisms in the glutathione S-transferase omega1 and methylenetetrahydrofolate reductase genes, the percentage of monomethylarsonous acid (%MMA) and dimethylarsinic acid (%DMA) in urine, and the ratios of MMA to inorganic arsenic and DMA to MMA. Water arsenic concentration was positively associated with %MMA and inversely associated with %DMA. The dose-response relationship of risk of skin lesion with %MMA was more apparent than those with other methylation indices; the ORs for skin lesions in relation to increasing %MMA quartiles were 1.00 (reference), 1.33 [95% confidence interval (95% CI), 0.92-1.93], 1.68 (95% CI, 1.17-2.42), and 1.57 (95% CI, 1.10-2.26; P for trend = 0.01). The ORs for skin lesions in relation to the methylenetetrahydrofolate reductase 677TT/1298AA and 677CT/1298AA diplotypes (compared with 677CC/1298CC diplotype) were 1.66 (95% CI, 1.00-2.77) and 1.77 (95% CI, 0.61-5.14), respectively. The OR for skin lesions in relation to the glutathione S-transferase omega1 diplotype containing all at-risk alleles was 3.91 (95% CI, 1.03-14.79). Analysis of joint effects of genotypes/diplotypes with water arsenic concentration and urinary %MMA suggests additivity of these factors. The findings suggest that arsenic metabolism, particularly the conversion of MMA to DMA, may be saturable and that differences in urinary arsenic metabolites, genetic factors related to arsenic metabolism, and their joint distributions modulate arsenic toxicity. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1270-8).
— id: 72860, year: 2007, vol: 16, page: 1270, stat: Journal Article,

Socioeconomic status and risk for arsenic-related skin lesions in Bangladesh
Argos, Maria; Parvez, Faruque; Chen, Yu; Hussain, A Z M Iftikhar; Momotaj, Hassina; Howe, Geoffrey R; Graziano, Joseph H; Ahsan, Habibul
2007 May;97(5):825-831, American journal of public health. AJPH
OBJECTIVES: Arsenic contamination of groundwater is a severe public health crisis in Bangladesh, where the population is exposed to arsenic in drinking water through tube wells used for groundwater collection. In this study, we explored the association between socioeconomic status and arsenic toxicity. METHODS: We used baseline data from 11438 men and women who were recruited into the Health Effects of Arsenic Longitudinal Study (HEALS), a prospective cohort study on the health effects of arsenic exposure in Bangladesh. We conducted analyses with logistic regression and generalized estimating equations. RESULTS: We found a strong dose-response association with all measures of arsenic exposure and skin lesions. We also found that the effect of arsenic was modified by land ownership on a multiplicative scale, with an increased risk among non-land owners associated with well water arsenic (P=.04) and urinary total arsenic concentrations (P=.03). CONCLUSIONS: Our study provides insight into potentially modifiable host characteristics and identifies factors that may effectively target susceptible population subgroups for appropriate interventions
— id: 71635, year: 2007, vol: 97, page: 825, stat: Journal Article,

Imputation of Missing Ages in Pedigree Data
Balise, Raymond R; Chen, Yu; Dite, Gillian; Felberg, Anna; Sun, Limei; Ziogas, Argyrios; Whittemore, Alice S
2007 Feb 19;63(3-4):168-174, Human heredity
Background: In human pedigree data age at disease occurrence frequently is missing and is imputed using various methods. However, little is known about the performance of these methods when applied to families. In particular, there is little information about the level of agreement between imputed and actual values of temporal data and their effects on inferences. Methods: We performed two evaluations of five imputation methods used to generate complete data for repositories to be shared by many investigators. Two of the methods are mean substitution methods, two are regression methods and one is a multiple imputation method based on one of the regression methods. To evaluate the methods, we randomly deleted the years of disease diagnosis of some men in a sample of pedigrees ascertained as part of a prostate cancer study. In the first evaluation, we used the five methods to impute the missing diagnosis years and evaluated agreement between imputed and actual values. In the second evaluation, we compared agreement between regression coefficients estimated using imputed diagnosis years with those estimated using the actual years. Results/Conclusions: For both evaluations, we found optimal or near-optimal performance from a regression method that imputes a man's diagnosis year based on the year of birth and year of last observation of all affected men with complete data. The multiple imputation analogue of this method also performed well.
— id: 70550, year: 2007, vol: 63, page: 168, stat: Journal Article,

Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia
Chambers, Mark S; Jones, Christopher Uwe; Biel, Merrill A; Weber, Randal S; Hodge, Kenneth M; Chen, Y; Holland, John M; Ship, Jonathan A; Vitti, Robert; Armstrong, Ingrid; Garden, Adam S; Haddad, Robert
2007 Dec 1;69(5):1369-1376, International journal of radiation oncology biology physics
PURPOSE: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. METHODS AND MATERIALS: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). RESULTS: Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). CONCLUSIONS: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region
— id: 150814, year: 2007, vol: 69, page: 1369, stat: Journal Article,

Inverse Associations of Helicobacter pylori With Asthma and Allergy
Chen, Yu; Blaser, Martin J
2007 Apr 23;167(8):821-827, Archives of internal medicine
BACKGROUND: Acquisition of Helicobacter pylori, which predominantly occurs before age 10 years, may reduce risks of asthma and allergy. METHODS: We evaluated the associations of H pylori status with history of asthma and allergy and with skin sensitization using data from 7663 adults in the Third National Health and Nutrition Examination Survey. Adjusted odds ratios (ORs) for currently and ever having asthma, allergic rhinitis, allergy symptoms in the previous year, and allergen-specific skin sensitization were computed comparing participants seropositive for cagA(-) or cagA(+) strains of H pylori with those without H pylori. RESULTS: The presence of cagA(+) H pylori strains was inversely related to ever having asthma (OR, 0.79; 95% confidence interval [CI], 0.63-0.99), and the inverse association of cagA positivity with childhood-onset (age </=15 years) asthma was stronger (OR, 0.63; 95% CI, 0.43-0.93) than that with adult-onset asthma (OR, 0.97; 95% CI, 0.72-1.32). Colonization with H pylori, especially with a cagA(+) strain, was inversely associated with currently (OR, 0.77; 95% CI, 0.62-0.96) or ever (OR, 0.77; 95% CI, 0.62-0.94) having a diagnosis of allergic rhinitis, especially for childhood onset (OR, 0.55; 95% CI, 0.37-0.82). Consistent inverse associations were found between H pylori colonization and the presence of allergy symptoms in the previous year and sensitization to pollens and molds. CONCLUSION: These observations support the hypothesis that childhood acquisition of H pylori is associated with reduced risks of asthma and allergy
— id: 71638, year: 2007, vol: 167, page: 821, stat: Journal Article,

Arsenic exposure from drinking water, dietary intakes of B vitamins and folate, and risk of high blood pressure in Bangladesh: a population-based, cross-sectional study
Chen, Yu; Factor-Litvak, Pam; Howe, Geoffrey R; Graziano, Joseph H; Brandt-Rauf, Paul; Parvez, Faruque; van Geen, Alexander; Ahsan, Habibul
2007 Mar 1;165(5):541-552, American journal of epidemiology
The authors performed a cross-sectional analysis to evaluate the association between arsenic exposure from drinking water and blood pressure using baseline data of 10,910 participants in the Health Effects of Arsenic Longitudinal Study in Bangladesh (October 2000-May 2002). A time-weighted well arsenic concentration (TWA) based on current and past use of drinking wells was derived. Odds ratios for high pulse pressure (> or = 55 mmHg) by increasing TWA quintiles (< or = 8, 8.1-40.8, 40.9-91.0, 91.1-176.0, and 176.1-864.0 microg/liter) were 1.00 (referent), 1.39 (95% confidence interval (CI): 1.14, 1.71), 1.21 (95% CI: 0.99, 1.49), 1.19 (95% CI: 0.97, 1.45), and 1.19 (95% CI: 0.97, 1.46). Among participants with a lower than average dietary intake level of B vitamins and folate, the odds ratios for high pulse pressure by increasing TWA quintiles were 1.00 (referent), 1.84 (95% CI: 1.07, 3.16), 1.89 (95% CI: 1.11, 3.20), 1.83 (95% CI: 1.09, 3.07), and 1.89 (95% CI: 1.12, 3.20). The odds ratios for systolic hypertension suggest a similar but weaker association. No apparent associations were observed between TWA and general or diastolic hypertension. These findings indicate that the effect of low-level arsenic exposure on blood pressure is nonlinear and may be more pronounced in persons with lower intake of nutrients related to arsenic metabolism and cardiovascular health. Future research is needed to evaluate the effect of low-level arsenic exposure on specific cardiovascular outcomes
— id: 71634, year: 2007, vol: 165, page: 541, stat: Journal Article,

A prospective study of blood selenium levels and the risk of arsenic-related premalignant skin lesions
Chen, Yu; Hall, Marni; Graziano, Joseph H; Slavkovich, Vesna; van Geen, Alexander; Parvez, Faruque; Ahsan, Habibul
2007 Feb;16(2):207-213, Cancer epidemiology biomarkers & prevention
Arsenic exposure from drinking water is considered to be a risk factor for skin and internal cancers. Animal studies suggest a potential antagonism between arsenic and selenium in the body. We did a case-cohort analysis to prospectively evaluate the association between arsenic-related premalignant skin lesions and prediagnostic blood selenium levels in 303 cases of skin lesions newly diagnosed from November 2002 to April 2004 and 849 subcohort members randomly selected from the 8,092 participants in the Health Effects of Arsenic Longitudinal Study with available baseline blood and urine samples collected in 2000. Incidence rate ratios for skin lesions in increasing blood selenium quintiles were 1.00 (reference), 0.68 [95% confidence interval (95% CI), 0.39-1.18], 0.51 (95% CI, 0.29-0.87), 0.52 (95% CI, 0.30-0.91), and 0.53 (95% CI, 0.31-0.90). Effect estimates remained similar with adjustments for age, sex, body mass index, smoking status, excessive sunlight exposure (in men), well water arsenic concentration at baseline, and nutritional intakes of folate, iron, protein, vitamin E, and B vitamins. At any given arsenic exposure level, the risk of premalignant skin lesions was consistently greater among participants with blood selenium lower than the average level. The findings support the hypothesis that dietary selenium intake may reduce the incidence of arsenic-related premalignant skin lesions among populations exposed to arsenic exposure from drinking water. (Cancer Epidemiol Biomarkers Prev 2007;16(2):207-13)
— id: 70551, year: 2007, vol: 16, page: 207, stat: Journal Article,

Association between arsenic exposure from drinking water and plasma levels of soluble cell adhesion molecules
Chen, Yu; Santella, Regina M; Kibriya, Muhammad G; Wang, Qiao; Kappil, Maya; Verret, Wendy J; Graziano, Joseph H; Ahsan, Habibul
2007 Oct;115(10):1415-1420, Environmental health perspectives
BACKGROUND: Epidemiologic studies of cardiovascular disease risk factors and appropriate biomarkers in populations exposed to a wide range of arsenic levels are a public health research priority. OBJECTIVE: We investigated the relationship between inorganic arsenic exposure from drinking water and plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), both markers of endothelial dysfunction and vascular inflammation, in an arsenic-exposed population in Araihazar, Bangladesh. METHODS: The study participants included 115 individuals with arsenic-related skin lesions participating in a 2 x 2 randomized, placebo-controlled, double-blind trial of vitamin E and selenium supplementation. Arsenic exposure status and plasma levels of sICAM-1 and sVCAM-1 were assessed at baseline and after 6 months of follow-up. RESULTS: Baseline well arsenic, a long-term measure of arsenic exposure, was positively associated with baseline levels of both sICAM-1 and sVCAM-1 and with changes in the two markers over time. At baseline, for every 1-mug/L increase in well arsenic there was an increase of 0.10 ng/mL [95% confidence interval (CI), 0.00-0.20] and 0.33 ng/mL (95% CI, 0.15-0.51) in plasma sICAM-1 and sVCAM-1, respectively. Every 1-microg/L increase in well arsenic was associated with a rise of 0.11 ng/mL (95% CI, 0.01-0.22) and 0.17 ng/mL (95% CI, 0.00-0.35) in sICAM-1 and sVCAM-1 from baseline to follow-up, respectively, in spite of recent changes in urinary arsenic as well as vitamin E and selenium supplementation during the study period. CONCLUSIONS: The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation that persists over time and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease
— id: 75254, year: 2007, vol: 115, page: 1415, stat: Journal Article,

Reduction in urinary arsenic levels in response to arsenic mitigation efforts in Araihazar, Bangladesh
Chen, Yu; van Geen, Alexander; Graziano, Joseph H; Pfaff, Alexander; Madajewicz, Malgosia; Parvez, Faruque; Hussain, A Z M Iftekhar; Slavkovich, Vesna; Islam, Tariqul; Ahsan, Habibul
2007 Jun;115(6):917-923, Environmental health perspectives
BACKGROUND: There is a need to identify and evaluate an effective mitigation program for arsenic exposure from drinking water in Bangladesh. OBJECTIVE: We evaluated the effectiveness of a multifaceted mitigation program to reduce As exposure among 11,746 individuals in a prospective cohort study initiated in 2000 in Araihazar, Bangladesh, by interviewing participants and measuring changes in urinary As levels. METHODS: The interventions included a) person-to-person reporting of well test results and health education; b) well labeling and village-level health education; and c) installations of 50 deep, low-As community wells in villages with the highest As exposure. RESULTS: Two years after these interventions, 58% of the 6,512 participants with unsafe wells (As >/=50 microg) at baseline had responded by switching to other wells. Well labeling and village-level health education was positively related to switching to safe wells (As < 50 mug/L) among participants with unsafe wells [rate ratio (RR) = 1.84; 95% confidence interval (CI), 1.60-2.11] and inversely related to any well switching among those with safe wells (RR = 0.80; 95% CI, 0.66-0.98). The urinary As level in participants who switched to a well identified as safe (< 50 microg As/L) dropped from an average of 375 microg As/g creatinine to 200 microg As/g creatinine, a 46% reduction toward the average urinary As content of 136 microg As/g creatinine for participants that used safe wells throughout. Urinary As reduction was positively related to educational attainment, body mass index, never-smoking, absence of skin lesions, and time since switching (p for trend < 0.05). CONCLUSIONS: Our study shows that testing of wells and informing households of the consequences of As exposure, combined with installation of deep community wells where most needed, can effectively address the continuing public health emergency from arsenic in drinking water in Bangladesh
— id: 73397, year: 2007, vol: 115, page: 917, stat: Journal Article,

Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer
Greenlee, Heather; Chen, Yu; Kabat, Geoffrey C; Wang, Qiao; Kibriya, Muhammad G; Gurvich, Irina; Sepkovic, Daniel W; Bradlow, H Leon; Senie, Ruby T; Santella, Regina M; Ahsan, Habibul
2007 Mar;102(1):111-117, Breast cancer research & treatment
We examined associations between polymorphisms in genes related to estrogen metabolism (CYP1B1 codon 432G --> C rs#1056836, CYP1B1 codon 453A --> G rs#1800440, COMT codon 158G --> A rs#4680) and biosynthesis (CYP17 T --> C promoter rs#743572, CYP19 exon 4 TTTA repeat) and urinary estrogen metabolites (2-hydroxyestrogens (2-OHE), 16alpha-hydroxyestrone (16alpha-OHE1), and their ratio) in a pilot study of 64 pre- and post-menopausal women with a family history of breast cancer. Women were participants in the Metropolitan New York Registry of Breast Cancer Families, one of six international sites of the National Cancer Institute's Breast Cancer Family Registry. We used linear regression to examine the effects of genetic variants on log-transformed urinary estrogen metabolites. After adjusting for menopausal status, BMI, and age, carriers of the CYP1B1 codon 453G variant allele had 31.0% lower levels of 2-OHE (P-value = 0.05) and 40.2% lower levels of 16alpha-OHE1 (P = 0.01). Results were similar after restricting the analyses to pre-menopausal women (n = 41). Consistent with other studies, among pre-menopausal women, carriers of the COMT codon 158A variant allele had increased 2-OHE levels (P = 0.03) and an increased 2-OHE/16alpha-OHE1 ratio (P = 0.04); carriers of the CYP17 C promoter variant allele had increased 2-OHE levels (P = 0.08). To our knowledge this is the first report showing associations between the CYP1B1 codon 453G variant allele and urinary 2-OHE and 16alpha-OHE1 metabolites. Further larger studies should be conducted to confirm these results. Future identification of individuals with genetic polymorphisms that affect estrogen metabolism and biosynthesis may help characterize women at higher breast cancer risk and could guide breast cancer prevention strategies for those individuals
— id: 67438, year: 2007, vol: 102, page: 111, stat: Journal Article,

Consumption of folate-related nutrients and metabolism of arsenic in Bangladesh
Heck, Julia E; Gamble, Mary V; Chen, Yu; Graziano, Joseph H; Slavkovich, Vesna; Parvez, Faruque; Baron, John A; Howe, Geoffrey R; Ahsan, Habibul
2007 May;85(5):1367-1374, American journal of clinical nutrition
BACKGROUND: Inorganic arsenic (InAs) is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and this methylation facilitates urinary arsenic excretion. Previous studies suggest that persons with more complete methylation, characterized as greater proportions of DMA and lesser proportions of MMA and InAs in urine, have a lower risk of adverse arsenic-related health outcomes. OBJECTIVE: The purpose of this study was to examine whether the capacity to methylate arsenic differs by nutrient intake. DESIGN: Participants were 1016 Bangladeshi adults exposed to arsenic in drinking water. Nutrient intake was assessed with a validated food-frequency questionnaire. Multivariate regression analyses were used to examine associations of nutrients with urinary arsenic metabolite profiles. RESULTS: In multivariate analyses, higher intakes of cysteine, methionine, calcium, protein, and vitamin B-12 were associated with lower percentages of InAs and higher ratios of MMA to InAs in urine. Higher intakes of niacin (beta=0.22, P=0.02) and choline (beta=0.10, P=0.02) were associated with higher DMA-to-MMA ratios, after adjustment for age, sex, smoking, total urinary arsenic, and total energy intake. CONCLUSIONS: Findings from the current study show the influence of multiple nutrients on arsenic methylation. In particular, this study highlights the potential importance of dietary intakes of cysteine, methionine, niacin, vitamin B-12, and choline on health effects of arsenic by modulating its metabolism.
— id: 72859, year: 2007, vol: 85, page: 1367, stat: Journal Article,

Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in Bangladesh
Li, Y; Chen, Y; Slavkovic, V; Ahsan, H; Parvez, F; Graziano, J H; Brandt-Rauf, P W
2007 May-Jun;12(3):256-265, Biomarkers
Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p</=0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p </= 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions
— id: 71636, year: 2007, vol: 12, page: 256, stat: Journal Article,

Health Effects of Arsenic Longitudinal Study (HEALS): Description of a multidisciplinary epidemiologic investigation
Ahsan, Habibul; Chen, Yu; Parvez, Faruque; Argos, Maria; Hussain, Azm Iftikhar; Momotaj, Hassina; Levy, Diane; van Geen, Alexander; Howe, Geoffrey; Graziano, Joseph
2006 Mar;16(2):191-205, Journal of exposure analysis & environmental epidemiology
Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes, including premalignant and malignant skin tumors, total mortality, pregnancy outcomes, and children's cognitive development. In this paper, we provide descriptions of the study methods including study design, study population, data collection, response rates, and exposure and outcome assessments. We also present characteristics of the study participants including the distribution of exposure and the prevalence of skin lesion at baseline recruitment. A total of 11,746 married men and women between 18 and 75 years of age participated in the study at baseline (a response rate of 98%) and completed a full questionnaire interview that included a food frequency questionnaire, with a response rate of 98%. Among the 98% of the participants who completed the clinical evaluation, over 90% provided blood samples and spot urine samples. Higher educational status, male gender, and presence of premalignant skin lesions were associated with an increased likelihood of providing blood and urine samples. Older participants were less likely to donate a blood sample. About one-third of the participants consumed water from a well with As concentration in each of three groups: >100 mug/l, 25-100 mug/l, and <25 mug/l. Average urinary As concentrations were 140 and 136 mug/l for males and females, respectively. HEALS has several unique features, including a prospective study design, comprehensive assessments of both past and future changes in As exposure at the individual level, a large repository of biological samples, and a full dose range of As exposures in the study population. HEALS is a valuable resource for examining novel research questions on the health effects of As exposure.Journal of Exposure Analysis and Environmental Epidemiology advance online publication, 14 September 2005; doi:10.1038/sj.jea.7500449
— id: 61169, year: 2006, vol: 16, page: 191, stat: Journal Article,

Arsenic Exposure from Drinking Water and Risk of Premalignant Skin Lesions in Bangladesh: Baseline Results from the Health Effects of Arsenic Longitudinal Study
Ahsan, Habibul; Chen, Yu; Parvez, Faruque; Zablotska, Lydia; Argos, Maria; Hussain, Iftikhar; Momotaj, Hassina; Levy, Diane; Cheng, Zhongqi; Slavkovich, Vesna; van Geen, Alexander; Howe, Geoffrey R; Graziano, Joseph H
2006 Jun 15;163(12):1138-1148, American journal of epidemiology
Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions
— id: 64145, year: 2006, vol: 163, page: 1138, stat: Journal Article,

Nutritional influence on risk of high blood pressure in Bangladesh: a population-based cross-sectional study
Chen, Yu; Factor-Litvak, Pam; Howe, Geoffrey R; Parvez, Faruque; Ahsan, Habibul
2006 Nov;84(5):1224-1232, American journal of clinical nutrition
BACKGROUND: The nutritional determinants of hypertension in Bangladesh and other low-income countries are largely unknown. OBJECTIVE: We assessed the associations of general hypertension with nutrient intakes and diet patterns in Bangladesh. DESIGN: This was a cross-sectional analysis of 11 116 participants enrolled in the Health Effects of Arsenic Longitudinal Study in Bangladesh. Dietary intakes were measured by use of a validated food-frequency questionnaire. RESULTS: Three major dietary patterns were identified by using principal component analysis: 1) the 'balanced' pattern, which was characterized by rice, some meat, small fish, fruit, and vegetables; 2) the 'animal protein' pattern, which was more heavily weighted on meat, milk, poultry, eggs, bread, large fish, and fruit; and 3) the 'gourd and root vegetable' pattern, which consisted largely of squashes and root and leafy vegetables. Adjusted prevalence odds ratios for general hypertension in increasing quintiles of balanced pattern scores were 1.00 (reference), 0.81 (95% CI: 0.79, 0.97), 0.82 (0.68, 0.97), 0.79 (0.66, 0.94), and 0.71 (0.59, 0.85) (P for trend < 0.01). Prevalence odds ratios for general hypertension in increasing quintiles of animal protein pattern scores were 1.00 (reference), 1.30 (1.01, 1.52), 1.20 (1.01, 1.47), 1.22 (1.00, 1.44), and 1.21 (1.03, 1.49) (P for trend = 0.23). Markers of high socioeconomic status were positively associated with the animal protein pattern. CONCLUSION: Our findings suggest the importance of dietary patterns in general hypertension in a low-income population undergoing the early stage of the epidemiologic transition
— id: 69361, year: 2006, vol: 84, page: 1224, stat: Journal Article,

Modification of Risk of Arsenic-Induced Skin Lesions by Sunlight Exposure, Smoking, and Occupational Exposures in Bangladesh
Chen, Yu; Graziano, Joseph H; Parvez, Faruque; Hussain, Iftikhar; Momotaj, Hassina; van Geen, Alexander; Howe, Geoffrey R; Ahsan, Habibul
2006 Jul;17(4):459-467, Epidemiology
BACKGROUND:: The risk of skin lesions associated with arsenic exposure from drinking water in Bangladesh is considerably greater in men than in women. METHODS:: Using baseline data from 11,062 cohort members in the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, we performed a cross-sectional analysis to evaluate whether the association between arsenic exposure from drinking water and the risk of skin lesions is modified by tobacco smoking, excessive sunlight, the use of fertilizer, and the use of pesticides. A time-weighted well arsenic concentration was estimated for each participant by incorporating history of well use. Relative excess risk for interaction (RERI) and its 95% confidence intervals (CIs) were estimated using adjusted prevalence odds ratios. RESULTS:: We observed a synergistic effect between the highest level of arsenic exposure (>113 mug/L) and tobacco smoking on risk of skin lesions in men (RERI = 1.5 [95% CI = 0.3 to 2.7] overall and 1.7 [0.2 to 3.4] for the subpopulation with longer-term arsenic exposure). We also observed suggestive synergistic effects between higher levels (28.1-113.0 mug/L and 113.1-864.0 mug/L) of arsenic exposure and fertilizer use in men (RERI = 1.0 [-0.2 to 2.2] and 1.3 [-0.2 to 2.9] respectively). Furthermore, the risk of skin lesions associated with any given level of arsenic exposure was greater in men with excessive sun exposure. The patterns of effect estimates in women indicate similar-but-weaker interaction effects of arsenic exposure with tobacco smoking and fertilizer use. CONCLUSIONS:: These findings help explain why the risk of arsenic-related skin lesions was much greater in men than in women in Bangladesh. Because most arsenic-induced skin cancers arise from these skin lesions, treatment and remediation plans should take into consideration these etiologic cofactors.
— id: 64377, year: 2006, vol: 17, page: 459, stat: Journal Article,

Arsenic exposure from drinking-water and carotid artery intima-medial thickness in healthy young adults in Bangladesh
Chen, Yu; Hakim, Mohammad Enamul; Parvez, Faruque; Islam, Tariqul; Rahman, Atiar M; Ahsan, Habibul
2006 Jun;24(2):253-257, Journal of health, population, & nutrition
Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies
— id: 71637, year: 2006, vol: 24, page: 253, stat: Journal Article,

Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh
Gamble, Mary V; Liu, Xinhua; Ahsan, Habibul; Pilsner, J Richard; Ilievski, Vesna; Slavkovich, Vesna; Parvez, Faruque; Chen, Yu; Levy, Diane; Factor-Litvak, Pam; Graziano, Joseph H
2006 Nov;84(5):1093-1101, American journal of clinical nutrition
BACKGROUND: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water. To various degrees, ingested inorganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one-carbon metabolism; impaired methylation is associated with adverse health outcomes. Consequently, folate nutritional status may influence arsenic methylation and toxicity. OBJECTIVE: The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation. DESIGN: Two hundred adults in a rural region of Bangladesh, previously found to have low plasma concentrations of folate (</=9 nmol/L) were enrolled in a randomized, double-blind, placebo-controlled folic acid-supplementation trial. Plasma concentrations of folate and homocysteine and urinary concentrations of arsenic metabolites were analyzed at baseline and after 12 wk of supplementation with folic acid at a dose of 400 microg/d or placebo. RESULTS: The increase in the proportion of total urinary arsenic excreted as DMA in the folic acid group (72% before and 79% after supplementation) was significantly (P < 0.0001) greater than that in the placebo group, as was the reduction in the proportions of total urinary arsenic excreted as MMA (13% and 10%, respectively; P < 0.0001) and as InAs (15% and 11%, respectively; P < 0.001). CONCLUSIONS: These data indicate that folic acid supplementation to participants with low plasma folate enhances arsenic methylation. Because persons whose urine contains low proportions of DMA and high proportions of MMA and InAs have been reported to be at greater risk of skin and bladder cancers and peripheral vascular disease, these results suggest that folic acid supplementation may reduce the risk of arsenic-related health outcomes
— id: 69362, year: 2006, vol: 84, page: 1093, stat: Journal Article,

Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study
Hall, Marni; Chen, Yu; Ahsan, Habibul; Slavkovich, Vesna; van Geen, Alexander; Parvez, Faruque; Graziano, Joseph
2006 Aug 15;225(2-3):225-233, Toxicology
Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r=0.85) and with water As (WAs) (r=0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population
— id: 67437, year: 2006, vol: 225, page: 225, stat: Journal Article,

Prevalence of arsenic exposure from drinking water and awareness of its health risks in a Bangladeshi population: results from a large population-based study
Parvez, Faruque; Chen, Yu; Argos, Maria; Hussain, A Z M Iftikhar; Momotaj, Hassina; Dhar, Ratan; van Geen, Alexander; Graziano, Joseph H; Ahsan, Habibul
2006 Mar;114(3):355-359, Environmental health perspectives
We conducted a population-based prevalence survey in Araihazar, Bangladesh, to describe the distribution of arsenic exposure in a rural Bangladeshi population and to assess the population's awareness to this problem as well as to possible remediation options. Water samples from 5,967 contiguous tube wells in a defined geographic area were tested using laboratory-based methods. Additionally, for each well, the owner/caretaker (or a close relative) was interviewed regarding his or her awareness of the health consequences of As exposure. Arsenic exposure data and demographic characteristics for the 65,876 users of these wells were also collected from the 5,967 respondents. Among the 65,876 residents, more than half (54%) regularly consumed well water with an As concentration > or = 50 microg/L--above the acceptable government standard in Bangladesh. Respondents were 15-92 years of age, with an average age of 42 years, and 43% were male. Presence of awareness was significantly related to male sex, nonlabor head of household occupation, better housing, and having had the well tested for As concentration. Most respondents (92%) expressed a willingness to take steps to reduce their exposure, with switching to a safe well the most favored option (46.2%). Willingness to reduce exposure was positively related to awareness of the health risks of As. However, the association between awareness and switching to a safe well [odds ratio (OR) = 1.25; 95% confidence interval (CI), 1.01-1.54] was no stronger than the associations between awareness and using surface water (with or without treatments) (OR = 1.54; 95% CI, 1.22-1.95) or using an existing well after treatment or increasing the depth (OR = 1.34; 95% CI, 1.08-1.67). These findings suggest that health education programs may need to target individuals with lower socioeconomic status and that well switching should be encouraged with more appropriate health education. Increasing knowledge of the health consequences of As may be an important element in facilitating remediation
— id: 64151, year: 2006, vol: 114, page: 355, stat: Journal Article,

An epidemiologic study of hepatitis B virus infection among Asian Americans in New York City
Wan, K; Chen, Y; Tsang, T; Sherman, A; Tso, A; Korenblit, P; Son, S; Poon, E; Ramos, R; Tobias, H; Rey, M; Pollack, H
2006 JUN 1 ;163(11):S252-S252, American journal of epidemiology
— id: 68859, year: 2006, vol: 163, page: S252, stat: Journal Article,

Aflatoxin B(1) and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients
Zhang, Yu-Jing; Rossner, Pavel Jr; Chen, Yu; Agrawal, Meenakshi; Wang, Qiao; Wang, Lillian; Ahsan, Habibul; Yu, Ming-Whei; Lee, Po-Huang; Santella, Regina M
2006 Sep 1;119(5):985-991, International journal of cancer
Elevated aflatoxin B(1)-albumin adducts (AFB(1)-Alb) have been associated with an increased risk for HCC development. However, there are no studies in humans, correlating albumin adducts in blood with liver DNA adducts. Forty frozen tumor tissues and 39 paired plasma samples from HCC patients were collected in Taiwan, to determine the relationship between albumin adducts in blood and DNA adducts in liver tissue as well as mutations in p53 and methylation of p16. AFB(1)- and polycyclic aromatic hydrocarbon (PAH)-DNA adducts in tissue and albumin adducts in plasma were determined by immunohistochemistry and competitive ELISA, respectively. Plasma AFB(1)-Alb adducts in subjects with low, medium and high levels of AFB(1)-DNA adducts in tumor tissues were 51.0 +/- 36.5, 70.5 +/- 48.1 and 84.9 +/- 48.2 fmol/mg, respectively (p(trend) = 0.05). No significant correlation was found for PAH. Fourteen of 40 (36%) tissues were positive for mutant p53 protein by immunohistochemistry; 11 of 40 tissue DNA samples (28%) were positive for p53 mutations, but not their corresponding plasma DNAs. p16 was methylated in 24 of 40 (62%) tissues and 12 of 39 (32%) plasma DNAs. Significant correlations were observed between AFB(1)-Alb adducts and p53 mutations and p16 methylation. These data suggest that genetic, epigenetic and environmental exposure biomarkers in plasma may help in estimating the risk for the development of HCC. (c) 2006 Wiley-Liss, Inc
— id: 64144, year: 2006, vol: 119, page: 985, stat: Journal Article,

Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study
Ahsan, Habibul; Whittemore, Alice S; Chen, Yu; Senie, Ruby T; Hamilton, Steven P; Wang, Qiao; Gurvich, Irina; Santella, Regina M
2005 ;7(1):R71-R81, Breast cancer research
BACKGROUND: Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T-->C promoter polymorphism) and CYP19 (TTTA repeat polymorphism). METHODS: We conducted the study among 278 nuclear families containing one or more daughters with breast cancer, with a total of 1123 family members (702 with available constitutional DNA and questionnaire data and 421 without them). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry, one of the six centers of the National Cancer Institute's Breast Cancer Family Registry. We used likelihood-based statistical methods to examine allelic associations. RESULTS: We found the CYP19 allele with 11 TTTA repeats to be associated with breast cancer risk in these families. We also found that maternal (but not paternal) carrier status of CYP19 alleles with 11 repeats tended to be associated with breast cancer risk in daughters (independently of the daughters' own genotype), suggesting a possible in utero effect of CYP19. We found no association of a woman's breast cancer risk either with her own or with her mother's CYP17 genotype. CONCLUSION: This family-based study indicates that a woman's personal and maternal carrier status of CYP19 11 TTTA repeat allele might be related to increased breast cancer risk. However, because this is the first study to report an association between CYP19 11 TTTA repeat allele and breast cancer, and because multiple comparisons have been made, the associations should be interpreted with caution and need confirmation in future family-based studies
— id: 61162, year: 2005, vol: 7, page: R71, stat: Journal Article,

TGFBR1*6A may contribute to hereditary colorectal cancer
Bian, Yansong; Caldes, Trinidad; Wijnen, Juul; Franken, Patrick; Vasen, Hans; Kaklamani, Virginia; Nafa, Khedoudja; Peterlongo, Paolo; Ellis, Nathan; Baron, John A; Burn, John; Moeslein, Gabriela; Morrison, Patrick J; Chen, Yu; Ahsan, Habibul; Watson, Patrice; Lynch, Henry T; de la Chapelle, Albert; Fodde, Riccardo; Pasche, Boris
2005 May 1;23(13):3074-3078, Journal of clinical oncology
PURPOSE: TGFBR16A is a tumor susceptibility gene that increases breast, colon, and ovarian cancer risk. Fourteen percent of the general population carries TGFBR16A, and TGFBR16A homozygotes have a greater than 100% increased colon cancer risk compared with noncarriers. Low-penetrance genes such as TGFBR16A may account for a sizable proportion of familial colorectal cancer occurrences. To test this hypothesis, we determined whether TGFBR16A contributes to a proportion of mismatch repair (MMR) gene mutation-negative hereditary nonpolyposis colorectal cancer (HNPCC) patients. PATIENTS AND METHODS: A case-case study was performed of 208 index patients with HNPCC meeting the Amsterdam criteria. Patients were examined for mutations and genomic rearrangements in the MLH1, MSH2, and MSH6 genes and genotyped for TGFBR16A. Tumor microsatellite instability status was available for 95 patients. RESULTS: A total of 144 patients (69.2%) carried a deleterious mutation and were classified as positive for MMR gene mutation; 64 patients (30.8%) had no evidence of mutations and were classified as MMR negative. TGFBR16A allelic frequency was significantly higher among MMR-negative patients (0.195) than among MMR-positive patients (0.104; P = .011). The proportion of TGFBR16A homozygotes was nine-fold higher among MMR-negative (6.3%) than among MMR-positive patients (0.7%; P = .032). The highest TGFBR16A allelic frequency was found among MMR-negative patients with tumors exhibiting no microsatellite instability (0.211), and the lowest frequency was found among MMR-positive patients with tumors exhibiting microsatellite instability (0.121); the difference was not statistically significant (P = .17). CONCLUSION: TGFBR16A may be causally responsible for a proportion of HNPCC occurrences
— id: 61170, year: 2005, vol: 23, page: 3074, stat: Journal Article,

Osteopetrosis-like phenotype in latent TGF-beta binding protein 3 deficient mice
Dabovic, B; Levasseur, R; Zambuto, L; Chen, Y; Karsenty, G; Rifkin, D B
2005 Jul;37(1):25-31, Bone
LTBPs are extracellular matrix proteins resembling fibrillins. LTBP-1, 3, and 4 covalently bind latent TGF-beta and modulate tissue levels of this potent cytokine through regulation of its secretion, localization, and/or activation. To address LTBP function in vivo, we generated Ltbp-3 null mice. Ltbp-3-/- animals developed craniofacial abnormalities due to early ossification of the skull base synchondroses and displayed reduced body size. In addition, histological examination of Ltbp-3-/- skeletons revealed an increase in bone mass. The osteoblast numbers and mineral apposition rates were decreased in Ltbp-3-/- mice, whereas the osteoclast numbers were similar in null and wild type mice. Histological examination revealed persistence of cartilage remnants in Ltbp-3-/- trabecular bone. Taken together, these results indicate that the Ltbp-3-/- high bone mass phenotype was due to a defect in bone resorption. We hypothesize that lack of Ltbp-3 results in decreased levels of TGF-beta in bone and cartilage, which leads to compromised osteoclast function and decreased bone turnover
— id: 146003, year: 2005, vol: 37, page: 25, stat: Journal Article,

Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk
Kaklamani, Virginia G; Baddi, Lisa; Liu, Junjian; Rosman, Diana; Phukan, Sharbani; Bradley, Ciaran; Hegarty, Chris; McDaniel, Bree; Rademaker, Alfred; Oddoux, Carole; Ostrer, Harry; Michel, Loren S; Huang, Helen; Chen, Yu; Ahsan, Habibul; Offit, Kenneth; Pasche, Boris
2005 Apr 15;65(8):3454-3461, Cancer research
There is growing evidence that common variants of the transforming growth factor-beta (TGF-beta) signaling pathway may modify breast cancer risk. In vitro studies have shown that some variants increase TGF-beta signaling, whereas others have an opposite effect. We tested the hypothesis that a combined genetic assessment of two well-characterized variants may predict breast cancer risk. Consecutive patients (n = 660) with breast cancer from the Memorial Sloan-Kettering Cancer Center (New York, NY) and healthy females (n = 880) from New York City were genotyped for the hypomorphic TGFBR1*6A allele and for the TGFB1 T29C variant that results in increased TGF-beta circulating levels. Cases and controls were of similar ethnicity and geographic location. Thirty percent of cases were identified as high or low TGF-beta signalers based on TGFB1 and TGFBR1 genotypes. There was a significantly higher proportion of high signalers (TGFBR1/TGFBR1 and TGFB1*CC) among controls (21.6%) than cases (15.7%; P = 0.003). The odds ratio [OR; 95% confidence interval (95% CI)] for individuals with the lowest expected TGF-beta signaling level (TGFB1*TT or TGFB1*TC and TGFBR1*6A) was 1.69 (1.08-2.66) when compared with individuals with the highest expected TGF-signaling levels. Breast cancer risk incurred by low signalers was most pronounced among women after age 50 years (OR, 2.05; 95% CI, 1.01-4.16). TGFBR1*6A was associated with a significantly increased risk for breast cancer (OR, 1.46; 95% CI, 1.04-2.06), but the TGFB1*CC genotype was not associated with any appreciable risk (OR, 0.89; 95% CI, 0.63-1.21). TGFBR1*6A effect was most pronounced among women diagnosed after age 50 years (OR, 2.20; 95% CI, 1.25-3.87). This is the first study assessing the TGF-beta signaling pathway through two common and functionally relevant TGFBR1 and TGFB1 variants. This approach may predict breast cancer risk in a large subset of the population
— id: 61171, year: 2005, vol: 65, page: 3454, stat: Journal Article,

A randomized, double-blind placebo-controlled trial evaluating the effects of vitamin E and selenium on arsenic-induced skin lesions in Bangladesh
Verret, Wendy J; Chen, Yu; Ahmed, Alauddin; Islam, Tariqul; Parvez, Faruque; Kibriya, Muhammad G; Graziano, Joseph H; Ahsan, Habibul
2005 Oct;47(10):1026-1035, Journal of occupational & environmental medicine
OBJECTIVE: We sought to determine whether supplementation of vitamin E (alpha-tocopherol), selenium (L-selenomethionine), or their combination improves arsenical skin lesions. METHODS: A 2 x 2 randomized, placebo-controlled, double-blind trial among 121 men and women chronically exposed to arsenic in drinking water was conducted in rural Bangladesh. Participants were randomized to one of four treatment arms: vitamin E, selenium, vitamin E and selenium (combination), or placebo and were treated for 6 months. RESULTS: At baseline, the average skin lesion scores were 2.23, 2.26, and 2.63 and at follow-up, the average skin lesion scores went down to 2.00, 2.06, and 2.47 in those receiving vitamin E, selenium, and the combination, respectively. CONCLUSIONS: Supplementation with vitamin E and selenium, either alone or in combination, slightly improved skin lesion status, although the improvement was not statistically significant
— id: 61168, year: 2005, vol: 47, page: 1026, stat: Journal Article,

Inflammatory bowel disease in patients with celiac disease
Yang, Alice; Chen, Yu; Scherl, Ellen; Neugut, Alfred I; Bhagat, Govind; Green, Peter H R
2005 Jun;11(6):528-532, Inflammatory bowel diseases
BACKGROUND: Several case reports and series report an association between celiac disease and inflammatory bowel disease (IBD); however, there is no current data assessing this association. We therefore studied the occurrence of these conditions in a cohort of patients with celiac disease seen at a referral center. METHODS: A database of patients with celiac disease seen between 1981 and 2002 was analyzed. Only biopsy-proven adults were included. Patients who had endoscopic and pathologic evidence of IBD were identified, and their pathology was reviewed. Age- and sex-adjusted prevalence rate ratios were determined by comparing results with population-based prevalence data. RESULTS: Among 455 patients with celiac disease, IBD was identified in 10 (5 had ulcerative colitis and 5 had Crohn's disease). This represented an age- and sex-adjusted prevalence rate ratio for ulcerative colitis of 3.56 (95% confidence interval, 1.48-8.56) and for Crohn's disease of 8.49 (95% confidence interval, 3.53-20.42). CONCLUSION: Within our cohort of patients with celiac disease, IBD was significantly more common than in the general population
— id: 61175, year: 2005, vol: 11, page: 528, stat: Journal Article,

Silencing of glutathione S-transferase P1 by promoter hypermethylation and its relationship to environmental chemical carcinogens in hepatocellular carcinoma
Zhang, Yu-jing; Chen, Yu; Ahsan, Habibul; Lunn, Ruth M; Chen, Shu-Yuan; Lee, Po-huang; Chen, Chien-Jen; Santella, Regina M
2005 Apr 28;221(2):135-143, Cancer letters
Glutathione S-transferases (GSTs) are a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents. GSTpi is encoded by the GSTP1 gene. GSTP1 null mice show an increased risk of skin tumorigenesis induced by carcinogens. GSTP1 is transcriptionally silenced by promoter hypermethylation in several human cancers including hepatocellular carcinoma (HCC). Methylation-specific PCR (MSP) was used to analyze the GSTP1 promoter hypermethylation status of 83 hepatocellular carcinoma tissues from Taiwan. Hypermethylation was detected in 38 of 83 (46%) tumors. GSTP1 expression by immunohistochemical staining of HCC tissue samples was significantly associated with methylation status. The relationship between methylation status and clinical parameters and tumor markers including environmental exposure to aflatoxin B1(AFB1) and polycyclic aromatic hydrocarbons (PAH), measured as DNA adducts, was also investigated. A statistically significant association was found between GSTP1 promoter hypermethylation and the level of AFB1-DNA adducts in tumor tissue (OR 2.81, 95% CI 1.03-7.70); a marginally significant association was found for adjacent non-tumor tissue (OR 2.57, 95% CI 0.97-6.80). There was no association between GSTP1 hypermethylation and PAH-DNA adducts in tumor or adjacent non-tumor tissues. These results suggest that epigenetic inactivation of GSTP1 plays an important role in the development of HCC and exposure to environmental carcinogens may be related to altered methylation of genes involved in hepatocarcinogenesis. The mechanism by which environmental exposures induce epigenetic changes in HCC needs further analysis
— id: 61161, year: 2005, vol: 221, page: 135, stat: Journal Article,

A family-based genetic association study of variants in estrogen-metabolism genes COMT and CYP1B1 and breast cancer risk
Ahsan, Habibul; Chen, Yu; Whittemore, Alice S; Kibriya, Muhammad G; Gurvich, Irina; Senie, Ruby T; Santella, Regina M
2004 May;85(2):121-131, Breast cancer research & treatment
In this paper, we report findings from a family-based association study examining the association between polymorphisms in two key estrogen-metabolism genes CYP1B1 (codon 432 G --> C and codon 453 A --> G variants) and COMT (codon 158 G --> A variant) and female breast cancer. We conducted the study among 280 nuclear families containing one or more daughters with breast cancer with a total of 1124 family members (702 with available constitutional DNA and questionnaire data and 421 without). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry (MNYR) - one of the six centers of NCI's Breast Cooperative Family Registry. We used likelihood-based statistical methods to examine the allelic associations. We found none of the variant alleles of the CYP1B1 and COMT genes to be associated with breast cancer in these families. This was consistent with results from matched case-control analyses using all available sib-ships in these families. However, we found that parental carrier status of the CYP1B1 codon 453 variant G allele and the COMT codon 158 variant A allele was associated with breast cancer risk in daughters (independent of the daughters' own genotype). In conclusion, findings from this family-based study indicate that a woman's own CYP1B1 or COMT genotypes are not associated with her breast cancer risk. Although the study found that parental carrier status of certain CYP1B1 or COMT genotypes might be associated with daughter's breast cancer risk, the biological basis as well as independent confirmation of this finding need to be investigated in future larger family-based studies before making meaningful inferences
— id: 61163, year: 2004, vol: 85, page: 121, stat: Journal Article,

Cancer burden from arsenic in drinking water in Bangladesh
Chen, Yu; Ahsan, Habibul
2004 May;94(5):741-744, American journal of public health. AJPH
We assessed the potential burden of internal cancers due to arsenic exposure in Bangladesh. We estimated excess lifetime risks of death from liver, bladder, and lung cancers using an exposure distribution, death probabilities, and cancer mortality rates from Bangladesh and dose-specific relative risk estimates from Taiwan. Results indicated at least a doubling of lifetime mortality risk from liver, bladder, and lung cancers (229.6 vs 103.5 per 100 000 population) in Bangladesh owing to arsenic in drinking water
— id: 61174, year: 2004, vol: 94, page: 741, stat: Journal Article,

Validity of a food-frequency questionnaire for a large prospective cohort study in Bangladesh
Chen, Yu; Ahsan, Habibul; Parvez, Faruque; Howe, Geoffrey R
2004 Nov;92(5):851-859, British journal of nutrition
We have developed a thirty-nine-item semi-quantitative food-frequency questionnaire (FFQ) to assess the dietary consumption of 11,746 men and women in a prospective cohort study that evaluates the health effects of As from drinking water in Bangladesh. In order to validate the FFQ, two 7 d food diaries (FD) were completed for 189 randomly selected cohort participants in two different seasons of the year. Nutrient values were converted based on both the United States Department of Agriculture's National Nutrient Database and a food composition table for the Indian subcontinent. Pearson product-moment and Spearman non-parametric rank correlation coefficients comparing food and nutrient consumptions estimated from FFQ and 7 d FD were calculated based on log-transformed consumption values with or without adjustment for total energy and correction for within-individual variation. Correlations of macronutrients and common micronutrients including total fat, monounsaturated fat, polyunsaturated fat, saturated fat, protein, carbohydrate, dietary fibre, Na, K, vitamin B6, vitamin B12, riboflavin, Mn, thiamin and Fe were moderately good, ranging from 0.30 to 0.76. However, correlations of other micronutrients were weak (<0.30). Large seasonal variations in intakes of retinol equivalents and vitamin C were observed. This analysis documents the degree of validity of the FFQ in measuring specific nutrient intakes in the study population. To our knowledge, the present study is the first to document the validity of a FFQ with the use of 7 d FD in a Bangladeshi population
— id: 61172, year: 2004, vol: 92, page: 851, stat: Journal Article,

No major association between TGFBR1*6A and prostate cancer
Kaklamani, Virginia; Baddi, Lisa; Rosman, Diana; Liu, Junjian; Ellis, Nathan; Oddoux, Carole; Ostrer, Harry; Chen, Yu; Ahsan, Habibul; Offit, Kenneth; Pasche, Boris
2004 Sep 22;5:28-28, BMC genetics
Prostate cancer is the most commonly diagnosed cancer in men and one of the leading causes of cancer deaths. There is strong genetic evidence indicating that a large proportion of prostate cancers are caused by heritable factors but the search for prostate cancer susceptibility genes has thus far remained elusive. TGFBR1*6A, a common hypomorphic variant of the type I Transforming Growth Factor Beta receptor, is emerging as a tumor susceptibility allele that predisposes to the development of breast, colon and ovarian cancer. The association with prostate cancer has not yet been explored. A total of 907 cases and controls from New York City were genotyped to test the hypothesis that TGFBR1*6A may contribute to the development of prostate cancer. TGFBR1*6A allelic frequency among cases (0.086) was slightly higher than among controls (0.080) but the differences in TGFBR1*6A genotype distribution between cases and controls did not reach statistical significance (p = 0.67). Our data suggest that TGFBR1*6A does not contribute to the development of prostate cancer
— id: 61173, year: 2004, vol: 5, page: 28, stat: Journal Article,

Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalase
Ahsan, Habibul; Chen, Yu; Kibriya, Muhammad G; Islam, Mohammad N; Slavkovich, Vesna N; Graziano, Joseph H; Santella, Regina M
2003 Nov 10;201(1):57-65, Cancer letters
Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. We examined whether genetic susceptibility, as determined by single nucleotide polymorphisms -463G-->A and -262C-->T in the oxidative stress genes myeloperoxidase (MPO) and catalase (CAT), respectively, are associated with the risk of arsenic-induced hyperkeratotic skin lesions-precursors of skin cancer-in a case-control study in Bangladesh. Carriers of the susceptible MPO and CAT genotypes were at elevated risk (OR 2.1 and 95% CI 0.7-6.2 for MPO; OR 1.9 and 95% CI 0.8-4.7 for CAT) of hyperkeratosis after adjustment for arsenic exposure and other covariates. Subjects carrying the high-risk MPO genotype and with high arsenic exposure were at almost six times (OR 5.8; 95% CI 1.1-30.1) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Similarly, highly exposed subjects carrying the high-risk CAT genotype were at more than four times (OR 4.6; 95% CI 1.4-15.6) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Our findings, although based on small numbers, suggest that the oxidative stress genes MPO and CAT may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions
— id: 61164, year: 2003, vol: 201, page: 57, stat: Journal Article,

DNA repair gene XPD and susceptibility to arsenic-induced hyperkeratosis
Ahsan, Habibul; Chen, Yu; Wang, Qiao; Slavkovich, Vesna; Graziano, Joseph H; Santella, Regina M
2003 Jul 20;143(2):123-131, Toxicology letters
Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. An estimated 50-70 million people in Bangladesh have been chronically exposed to arsenic from drinking water and are at risk of skin and other cancers. We undertook the first study to examine whether genetic susceptibility, as determined by the codon 751 SNP (A-->C) of the DNA repair gene XPD, influences the risk of arsenic-induced hyperkeratotic skin lesions, precursors of skin cancer, in a case-control study of 29 hyperkeratosis cases and 105 healthy controls from the same community in an area of Bangladesh. As expected, there was a monotonic increase in risk of hyperkeratosis in relation to urinary arsenic measures but the XPD genotype was not independently associated with the risk. However, the increase in hyperkeratosis risk in relation to urinary arsenic measures genotype was borderline significant for urinary total arsenic (P for trend=0.06) and statistically significant for urinary creatinine adjusted arsenic (P for trend=0.01) among subjects with the XPD A allele (AA) but not among subjects with the other XPD genotypes. Among AA carriers, the risk for the highest arsenic exposed group compared with the lowest was more than 7-fold for urinary total arsenic and about 11-fold for urinary creatinine adjusted arsenic. In conclusion, our findings suggest that the DNA repair gene XPD may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions. Future larger studies are needed to confirm this novel finding and investigate how combinations of different candidate genes and/or other host and environmental factors may influence the risk of arsenic induced skin and other cancers
— id: 61165, year: 2003, vol: 143, page: 123, stat: Journal Article,

Lung cancer risk in white and black Americans
Stellman, Steven D; Chen, Yu; Muscat, Joshua E; Djordjevic, Mirjana V; Richie, John P Jr; Lazarus, Philip; Thompson, Seth; Altorki, Nasser; Berwick, Marianne; Citron, Marc L; Harlap, Susan; Kaur, Tajinder B; Neugut, Alfred I; Olson, Sara; Travaline, John M; Witorsch, Philip; Zhang, Zuo-Feng
2003 Apr;13(4):294-302, Annals of epidemiology
PURPOSE: To test whether differences in smoking-related lung cancer risks in blacks and whites can explain why lung cancer incidence is greater in black males than in white males but about equal in black and white females, given that a greater proportion of blacks are smokers, but smoke far fewer cigarettes per day than do whites. METHODS: A hospital-based case-control study was conducted between 1984 and 1998 that included interviews with 1,710 white male and 1,321 white female cases of histologically confirmed lung cancer, 254 black male and 163 black female cases, and 8,151 controls. Relative risks were estimated via odds ratios using logistic regression, adjusted for age, education, and body mass index. RESULTS. We confirmed prior reports that smoking prevalence is higher but overall dosage is lower among blacks. Overall ORs were similar for blacks and whites, except among the heaviest smoking males (21+ cigarettes per day or 37.5 pack-years), in whom ORs for blacks were considerably greater than for whites. Long-term benefits of cessation were similar for white and black ex-smokers. Smokers of menthol flavored cigarettes were at no greater risk for lung cancer than were smokers of unflavored brands. CONCLUSIONS. Lung cancer risks were similar for whites and blacks with similar smoking habits, except possibly for blacks who were very heavy smokers; this sub-group is unusual in the general population of African American smokers. Explanations of racial disparities in lung cancer risk may need to account for modifying factors including type of cigarette (yield, mentholation), diet, occupation, and host factors such as ability to metabolize mainstream smoke carcinogens
— id: 44881, year: 2003, vol: 13, page: 294, stat: Journal Article,

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B1-DNA adducts and p53 mutation in hepatocellular carcinoma
Zhang, Yu-Jing; Chen, Yu; Ahsan, Habibul; Lunn, Ruth M; Lee, Po-Huang; Chen, Chien-Jen; Santella, Regina M
2003 Feb 10;103(4):440-444, International journal of cancer
O(6)-methylguanine-DNA methyltransferase (MGMT) is a repair protein that specifically removes promutagenic alkyl groups from the O(6) position of guanine in DNA. MGMT is transcriptionally silenced by promoter hypermethylation in several human cancers. Methylation-specific PCR (MSP) was used to analyze the MGMT promoter methylation status of 83 hepatocellular carcinomas (HCC) and 2 HCC cell lines (HepG2 and Hep3B). Hypermethylation was detected in 32 of 83 (39%) HCC tissues, but it was not found in either HCC cell line. We also analyzed MGMT expression by immunohistochemical analysis of HCC tissue samples. The presence of aberrant hypermethylation was associated with loss of MGMT protein. The relationship between methylation status and risk factors and tumor markers including environmental exposure to aflatoxin B(1) (AFB(1)), measured as DNA adducts, and status of tumor suppressor gene p53 was also investigated. A statistically significant association was found between MGMT promoter hypermethylation and high level of AFB(1)-DNA adducts in tumor tissues (OR = 5.05, 95% CI = 1.29-19.73). A significant association was also found between methylation and p53 mutation status (OR = 2.97, 95% CI = 1.09-8.11). These results suggest that epigenetic inactivation of MGMT plays an important role in the development of HCC and exposure to environmental carcinogens may be related to altered methylation of genes involved in cancer development. The role of chemical carcinogens in hypermethylation needs further investigation
— id: 61166, year: 2003, vol: 103, page: 440, stat: Journal Article,

High frequency of promoter hypermethylation of RASSF1A and p16 and its relationship to aflatoxin B1-DNA adduct levels in human hepatocellular carcinoma
Zhang, Yu-Jing; Ahsan, Habibul; Chen, Yu; Lunn, Ruth M; Wang, Li-Yu; Chen, Shu-Yuan; Lee, Po-Huang; Chen, Chien-Jen; Santella, Regina M
2002 Oct;35(2):85-92, Molecular carcinogenesis
Epigenetic changes in gene expression due to extensive CpG island methylation is now accepted as the main cause of inactivation of the p16 gene. More recently, it has been suggested that the human ras association domain family (RASSF) 1 gene, cloned from the lung tumor-suppressor locus 3p21.3, also may be inactivated by methylation. It consists of two major alternative transcripts, RASSF1A and RASSF1C. Epigenetic inactivation of isoform A was observed in several carcinomas and tumor cell lines. In this study, promoter hypermethylation of RASSF1A and p16 was investigated in 83 hepatocellular carcinoma (HCC) tissue samples from Taiwan and in two HCC cell lines (Hep3B and HepG2). High frequencies (85% and 47%, respectively) of methylation of the CpG island promoters of RASSF1A and p16 were found in the HCC tissues. The methylation of RASSF1A also was detected in Hep3B cells but not in HepG2 cells; p16 was not methylated in either cell line. Methylation status was determined in 12 normal control liver tissues and 10 adjacent nontumor tissues. No methylation was found in normal liver control tissues for both RASSF1A and p16; methylation was detected in one of 10 and seven of 10 adjacent nontumor tissue sampless for p16 and RASSF1A, respectively, in subjects with positive tumors. These data indicate that aberrant methylation of the CpG island promoters of both genes is a frequent occurrence in hepatocarcinogenesis. The high frequency of RASSF1A methylation in adjacent tissues suggests that this may be an early event. The relationship between methylation status and clinical parameters and tumor markers, including DNA damage resulting from aflatoxin B(1) (AFB(1)), an environmental carcinogen, and p53 status, also was analyzed. A statistically significant association was found between RASSF1A methylation status and the level of AFB(1)-DNA adducts in tumor tissues. No association was found between methylation status and p53 status. These results suggest the hypothesis that exposure to environmental carcinogens may be involved in altered methylation of genes involved in cancer development
— id: 61167, year: 2002, vol: 35, page: 85, stat: Journal Article,

Cost-effectiveness analysis of long-term moderate exercise training in chronic heart failure
Georgiou D; Chen Y; Appadoo S; Belardinelli R; Greene R; Parides MK; Glied S
2001 Apr 15;87(8):984-988 A4, American journal of cardiology
The purpose of this study is to perform a cost-effectiveness analysis of long-term moderate exercise training (ET) in patients with stable chronic heart failure. In particular, the study focuses on the survival analysis and cost savings from the reduction in the hospitalization rate in the exercise group. In the past 10 years, ET has been shown to be beneficial for patients with stable class II and III heart failure in many randomized clinical trials. However, the cost-effectiveness of a long-term ET program has not been addressed for outcomes related to morbidity/mortality end points or health care utilization. We examined the cost-effectiveness of a 14-month long-term training in patients with stable chronic heart failure. The estimated increment cost for the training group, $3,227/patient, was calculated by subtracting the averted hospitalization cost, $1,336/patient, from the cost of ET and wage lost due to ET, estimated at $4,563/patient. For patients receiving ET, the estimated increment in life expectancy was 1.82 years/person in a time period of 15.5 years, compared with patients in the control group. The cost-effectiveness ratio for long-term ET in patients with stable heart failure was thus determined at $1,773/life-year saved, at a 3% discount rate. Long-term ET in patients with stable chronic heart failure is cost-effective and prolongs survival by an additional 1.82 years at a low cost of $1,773 per/life-year saved
— id: 61159, year: 2001, vol: 87, page: 984, stat: Journal Article,

Smoking and lung cancer risk in American and Japanese men: an international case-control study
Stellman SD; Takezaki T; Wang L; Chen Y; Citron ML; Djordjevic MV; Harlap S; Muscat JE; Neugut AI; Wynder EL; Ogawa H; Tajima K; Aoki K
2001 Nov;10(11):1193-1199, Cancer epidemiology biomarkers & prevention
Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking
— id: 61160, year: 2001, vol: 10, page: 1193, stat: Journal Article,

Changes in high-dose-rate tandem and ovoid applicator positions during treatment in an unfixed brachytherapy system
Pham, H T; Chen, Y; Rouby, E; Lustig, R A; Wallner, P E
1998 Feb;206(2):525-531, Radiology
PURPOSE: To measure the change in applicator position during treatment in an unfixed high-dose-rate (HDR) brachytherapy system and to evaluate the effect of the shifts on dose calculations. MATERIALS AND METHODS: Posttreatment localization radiographs were obtained for 47 HDR treatments (26 tandem and ovoid applicators, 21 ovoids-only applicators). The authors measured the change in applicator position relative to the patient's bone anatomy. Doses to the target and critical structures were calculated for posttreatment applicator positions for comparison. RESULTS: Average displacements of the tandem and ovoid applicators in anteroposterior dimension were 5 and 4 mm for the tandem and ovoids, respectively. Anterior displacement occurred twice as often as posterior displacement. The average lateral and longitudinal shifts were less. Less displacement was observed with ovoids-only insertions. The largest displacement for ovoids-only applicators was 3 mm in the anteroposterior dimension. A high bladder dose difference (17.4%) for tandem and ovoid applications correlated with anterior shifts of the applicators. CONCLUSION: Patient movement in an unfixed HDR brachytherapy system can displace the applicators, especially the tandem. Anterior shifts correlate with high bladder dose differences. Immobilization of the patient's hips and legs, as well as stabilization of applicators, would reduce these shifts
— id: 140206, year: 1998, vol: 206, page: 525, stat: Journal Article,

Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies
Chen, Y T; Stockert, E; Chen, Y; Garin-Chesa, P; Rettig, W J; van der Bruggen, P; Boon, T; Old, L J
1994 Feb 1;91(3):1004-1008, Proceedings of the National Academy of Sciences of the United States of America
The human MAGE-1 gene encodes a melanoma peptide antigen recognized by autologous cytotoxic T lymphocytes. To produce antibodies against the MAGE-1 gene product, several approaches were taken. Three oligopeptides were synthesized based on predicted MAGE-1 amino acid sequences and were used to generate rabbit anti-peptide anti-sera. In addition, a truncated MAGE-1 cDNA was cloned into an Escherichia coli expression vector, and recombinant protein was produced and purified. All three rabbit anti-peptide antisera showed reactivity against the immunizing peptide, and one reacted with the recombinant MAGE-1 protein by immunoblotting, but none reacted with cell lysates from MAGE-1 mRNA-positive cells. The recombinant MAGE-1 protein was then used for the generation of mouse monoclonal and rabbit polyclonal antibodies. One IgG1 monoclonal antibody, MA454, as well as rabbit polyclonal antisera recognized a 46-kDa protein in extracts of MAGE-1 mRNA-positive melanoma cell lines. The antibodies showed no apparent cross-reactivity with products of the closely related MAGE-2 and MAGE-3 genes. Serological typing of normal and tumor cell lysates was in full agreement with mRNA analysis, showing expression of MAGE-1 protein in MAGE-1 mRNA-positive testis and a subset of melanomas but not in MAGE-1 mRNA-negative normal or tumor tissues. Transfection of the MAGE-1 gene into a MAGE-1 mRNA-negative melanoma cell line resulted in the expression of the 46-kDa protein, confirming the identity of this protein as the MAGE-1 gene product
— id: 145137, year: 1994, vol: 91, page: 1004, stat: Journal Article,