Faculty Bibliography

PURPOSE: Taurine (2-aminoethanesulfonic acid), a molecule obtained from diet, is involved in bile acid conjugation, blood pressure regulation, anti-oxidation and anti-inflammation. We performed the first prospective study of taurine and CHD risk. METHODS: We conducted a case-control study nested in the New York University Women's Health Study to evaluate the association between circulating taurine levels and risk of coronary heart disease (CHD). Taurine was measured in two yearly pre-diagnostic serum samples of 223 CHD cases and 223 matched controls and averaged for a more reliable measurement of long-term taurine levels. RESULTS: Mean serum taurine was positively related to age and dietary intake of poultry, niacin, vitamin B1, fiber and iron, and negatively related to dietary intake of saturated fat (all p values 250 mg/dL) (adjusted OR = 0.39 (0.19-0.83) for the third versus first tertile; p for trend = 0.02) but not among those with low total serum cholesterol (p for interaction = 0.01). The data suggest a possible inverse association of serum taurine with diabetes and hypertension risk. CONCLUSIONS: The findings suggest that high levels of taurine may be protective against CHD among individuals with high serum cholesterol levels.

We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans) and dental caries (Streptococcus mutans and S. sobrinus). There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR) for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87-2.12), P. gingivalis (OR = 1.12, 0.67-1.88) and T. denticola (OR = 1.34, 0.83-2.12) measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13-5.56) among those with >/= median of percent tooth sites with PD>/=3 mm, compared with no association among those below the median (OR = 0.86, 0.43-1.72). A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03-0.06). Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions.

BACKGROUND: Limited data are available on smoking-related mortality in low-income countries, where both chronic disease burden and prevalence of smoking are increasing. METHODS: Using data on 20,033 individuals in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, we prospectively evaluated the association between tobacco smoking and all-cause, cancer, and cardiovascular disease mortality during approximately 7.6 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for deaths from all-cause, cancer, CVD, ischemic heart disease (IHD), and stroke, in relation to status, duration, and intensity of cigarette/bidi and hookah smoking. RESULTS: Among men, cigarette/bidi smoking was positively associated with all-cause (HR 1.40, 95% CI 1.06 1.86) and cancer mortality (HR 2.91, 1.24 6.80), and there was a dose-response relationship between increasing intensity of cigarette/bidi consumption and increasing mortality. An elevated risk of death from ischemic heart disease (HR 1.87, 1.08 3.24) was associated with current cigarette/bidi smoking. Among women, the corresponding HRs were 1.65 (95% CI 1.16 2.36) for all-cause mortality and 2.69 (95% CI 1.20 6.01) for ischemic heart disease mortality. Similar associations were observed for hookah smoking. There was a trend towards reduced risk for the mortality outcomes with older age at onset of cigarette/bidi smoking and increasing years since quitting cigarette/bibi smoking among men. We estimated that cigarette/bidi smoking accounted for about 25.0% of deaths in men and 7.6% in women. CONCLUSIONS: Tobacco smoking was responsible for substantial proportion of premature deaths in the Bangladeshi population, especially among men. Stringent measures of tobacco control and cessation are needed to reduce tobacco-related deaths in Bangladesh.

Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk.

BACKGROUND: We utilized data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, to evaluate the association of steamed rice consumption with urinary total arsenic concentration and arsenical skin lesions in the overall study cohort (N=18,470) and in a subset with available urinary arsenic metabolite data (N=4,517). METHODS: General linear models with standardized beta coefficients were used to estimate associations between steamed rice consumption and urinary total arsenic concentration and urinary arsenic metabolites. Logistic regression models were used to estimate prevalence odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations between rice intake and prevalent skin lesions at baseline. Discrete time hazard models were used to estimate discrete time (HRs) ratios and their 95% CIs for the associations between rice intake and incident skin lesions. RESULTS: Steamed rice consumption was positively associated with creatinine-adjusted urinary total arsenic (beta=0.041, 95% CI: 0.032-0.051) and urinary total arsenic with statistical adjustment for creatinine in the model (beta=0.043, 95% CI: 0.032-0.053). Additionally, we observed a significant trend in skin lesion prevalence (P-trend=0.007) and a moderate trend in skin lesion incidence (P-trend=0.07) associated with increased intake of steamed rice. CONCLUSIONS: This study suggests that rice intake may be a source of arsenic exposure beyond drinking water.

Risk of skin lesions due to chronic arsenic exposure can be further affected by nutrient intake. We prospectively evaluated the association of nutrient intake and gender with incident skin lesions using data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh. Discrete time hazard models were used to estimate these effects in stratified analyses based on skin lesion severity. Overall, we observed significant associations between low intakes of various nutrients (retinol, calcium, fiber, folate, iron, riboflavin, thiamin, and vitamins A, C, and E) and skin lesion incidence, particularly for keratotic skin lesions. Associations for vitamins C and E showed significant linear trends. Gender-specific analyses revealed an inverse association between the lowest quartile of nutrient intake and keratotic skin lesion incidence for retinol equivalents, calcium, folate, iron, and fiber among women. Interactions by gender were observed for retinol equivalents (P-interaction = 0.03), calcium (P-interaction = 0.04), vitamin A (P-interaction = 0.03), and riboflavin (P-interaction = 0.04) with the incidence of keratotic skin lesions. Understanding differential susceptibility to skin lesion incidence based on nutrient intake will help researchers develop targeted interventions to prevent health consequences of arsenic poisoning in Bangladesh and beyond.

Background: The effects of arsenic exposure from drinking water at levels < 300 mug/L on diabetes remains controversial. Objectives: To evaluate the associations of well water arsenic and total urinary arsenic with the prevalence of diabetes mellitus and glucosuria. Methods: 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. We also assessed the relationship of arsenic exposure and the composition of urinary arsenic metabolites with blood glycosylated hemoglobin (HbA1c) levels in a subset of 2,100 participants. Results: 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 > 177 mug/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 > 205 mug/L, respectively. We observed no association between arsenic exposure and prevalence of glucosuria and no evidence of an association between arsenic exposure or the composition of urinary arsenic metabolites and HbA1c levels. 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

Background: Limited evidence exists for the effects of arsenic on lung function and tuberculosis particularly those exposed to low-to-moderate levels of arsenic exposure. Methods: We conducted a population-based study to evaluate the association between arsenic exposure, measured in well water and urine samples, and pulmonary function in 1,042 Health Effects of Arsenic Longitudinal Study (HEALS) participants in Araihazar, Bangladesh. Results: We have observed baseline water arsenic exposure to be inversely associated with reduced Forced Expiratory Volume in 1 second (FEV1) (-46.52 ml, p<0.0005) and Forced Vital Capacity (FVC) (-53.10 ml, p<0.01) in models adjusted for age, sex, body mass index, smoking, socioeconomic status, and skin lesions status. Similar inverse relationship were observed between baseline urinary arsenic and FEV1 (-48.35 ml, p<0.005) and FVC (-55.23 ml, p<0.01) in adjusted models. In cohort analyses, 237 tuberculosis cases were observed during the follow-up, and a dose-response relationship between arsenic exposure and the risk of tuberculosis was observed. As compared to those at the lowest quartile of well water arsenic (<=5.5 mug/L), the hazard ratio (HRs) of tuberculosis were 1.08 (95% CI: 0.75-1.62), 1.17 (95% CI: 0.81-1.71), and 1.27 (95% CI: 0.84-1.83), for the 2nd-4th quintiles of baseline water arsenic concentration (5.5-43.2, 43.2-116, >116 mug/L), respectively. Risks of increased tuberculosis associated with well arsenic concentration were comparable with that related to baseline urinary arsenic. Conclusion: Our study demonstrates for the first time in a large cohort that low-to-moderate levels of water arsenic may increase risk of impaired lung function and tuberculosis