Faculty Bibliography

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

In Latin America, several regions have a long history of widespread arsenic (As) contamination from both natural and anthropological sources. Yet, relatively little is known about the extent of As exposure from drinking water and its related health consequences in these countries. It has been estimated that at least 4.5 million people in Latin America are chronically exposed to high levels of As (>50 mug/L), some to as high as 2000 mug/L--200 times higher than the World Health Organization (WHO) provisional standard for drinking water. We conducted a systematic review of 82 peer reviewed papers and reports to fully explore the current understanding of As exposure and its health effects, as well as the influence of genetic factors that modulate those effects in the populations of Latin America. Despite some methodological limitations, these studies suggested important links between the high levels of chronic As exposure and elevated risks of numerous adverse health outcomes in Latin America--including internal and external cancers, reproductive outcomes, and childhood cognitive function. Several studies demonstrated genetic polymorphisms that influence susceptibility to these and other disease states through their modulation of As metabolism, with As methyltransferase (AS3MT), glutathione S-transferase (GST), and genes of one-carbon metabolism being specifically implicated. While the full extent and nature of the health burden are yet to be known in Latin America, these studies have significantly enriched knowledge of As toxicity and led to subsequent research. Targeted future studies will not only yield a better understanding of the public health impact of As in Latin America populations, but also allow for effective and timely mitigation efforts.

The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007-2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln mug/L) and urinary arsenic (ln mug/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.