Arsenic is a carcinogen, a Superfund toxic compound, and a common drinking-water contaminant. The Environmental Protection Agency (EPA) has identified 1,300 sites on its National Priorities List (NPL) and arsenic has been found in at least 781 of these sites in the USA. Exposure may occur by a variety of pathways including inhalation of dusts in air, ingestion of contaminated soil or water, or through the food chain. The primary mode of exposure in non-occupationally exposed populations is drinking-water contamination from either alluvial deposits or industrial contamination. The precise relation of arsenic to cancer has not been established at low exposure levels. In addition, arsenic toxicokinetics in humans remains poorly understood. Thus, we propose to assess exposure and skin-lesion risk, as well as arsenic dosimetrics in a population with a wide range of arsenic exposure via drinking-water contamination. The proposal builds upon a small study in which a case-control study has been initiated. This proposal will use the necessary resources to analyze biomarkers of exposure and susceptibility and for statistical analyses of both a case-control study of skin lesions and a repeated-measures biomarker dosimetry study. The proposed studies in Bangladesh will assess this risk in a population with a wide range of exposures - from low to very high. Together, these data will add substantially to the existing risk assessment information by elucidating both early and late outcomes alter arsenic exposure, and the influence of susceptibility traits at all levels of exposure. This project is relevant to the overall aims of NIEHS in several ways: First, we will examine a range of health effects of an important environmental carcinogen. Second, we will define human biomarkers of exposure, early effects, and genetic susceptibility to arsenic exposure. Third, we will examine exposure-response relationships for arsenic-induced non-malignant skin lesions as well as for skin cancers.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Gray, Kimberly A
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Harvard University
Public Health & Prev Medicine
Schools of Public Health
United States
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Lee, Jane J; Valeri, Linda; Kapur, Kush et al. (2018) Growth parameters at birth mediate the relationship between prenatal manganese exposure and cognitive test scores among a cohort of 2- to 3-year-old Bangladeshi children. Int J Epidemiol 47:1169-1179
Matthews, Natalie H; Fitch, Katherine; Li, Wen-Qing et al. (2018) Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies. Cancer Epidemiol Biomarkers Prev :
Lin, Pi-I D; Bromage, Sabri; Mostofa, Md Golam et al. (2017) Associations between Diet and Toenail Arsenic Concentration among Pregnant Women in Bangladesh: A Prospective Study. Nutrients 9:
Lee, Jane J; Kapur, Kush; Rodrigues, Ema G et al. (2017) Anthropometric measures at birth and early childhood are associated with neurodevelopmental outcomes among Bangladeshi children aged 2-3years. Sci Total Environ 607-608:475-482
Kile, Molly L; Faraj, Joycelyn M; Ronnenberg, Alayne G et al. (2016) A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women. BMC Public Health 16:158
Rodrigues, Ema G; Bellinger, David C; Valeri, Linda et al. (2016) Neurodevelopmental outcomes among 2- to 3-year-old children in Bangladesh with elevated blood lead and exposure to arsenic and manganese in drinking water. Environ Health 15:44
Huque, Md Hamidul; Carroll, Raymond J; Diao, Nancy et al. (2016) Exposure Enriched Case-Control (EECC) Design for the Assessment of Gene-Environment Interaction. Genet Epidemiol 40:570-578
Seow, Wei Jie; Kile, Molly L; Baccarelli, Andrea A et al. (2014) Epigenome-wide DNA methylation changes with development of arsenic-induced skin lesions in Bangladesh: a case-control follow-up study. Environ Mol Mutagen 55:449-56
Pan, Wen-Chi; Kile, Molly L; Seow, Wei Jie et al. (2013) Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes. PLoS One 8:e70792
Pan, Wen-Chi; Seow, Wei Jie; Kile, Molly L et al. (2013) Association of low to moderate levels of arsenic exposure with risk of type 2 diabetes in Bangladesh. Am J Epidemiol 178:1563-70

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