Nearly 100 million people in the world, including approximately 57 million in Bangladesh and about 15 million in the U.S., are chronically exposed to inorganic arsenic, a Class I human carcinogen, and are at increased risk of skin andother arsenic-induced cancers?as well as cardiovascular, pulmonary and other non-malignant disorders.As part of the Columbia University Superfund Basic Research Program, we have established Health Effectsof Arsenic Longitudinal Study (HEALS)?a large prospective cohort study based on individual level dataamong a population exposed to a wide range of inorganic arsenic (InAs) from drinking water in Araihazar,Bangladesh. Over the past five years, using a population-based sampling frame, we recruited 11,754 menand women (with >99% response rates) and collected detailed questionnaires, clinical data, andbiospecimen samples from them at baseline, two years and four years after recruitment. Through adedicated medical clinic established by Columbia University to exclusively serve the HEALS participants, wehave also developed an effective mechanism of following the cohort, especially for detecting incidence andmortality of dermatological, pulmonary, and cardiovascular disorders (CVD). In this proposal, we proposedto prospectively evaluate the effects of various measures of As exposure and metabolism on: i) incidence ofskin lesions and skin cancer, ii) incidence and mortality from chronic lung disorders and mortality from lungcancers, iii) incidence and mortality from CVD, iv) serum levels of the epidermal growth factor receptor (asan early biomarker of As-induced skin carcinogenesis), v) serum levels of bronchial/alveolar cell-derivedantioxidant Clara cell protein 16 (as an early biomarker of As-induced chronic lung damage andcarcinogenesis), and vi) carotid artery intima-medial thickness (as early preclinical marker of As-inducedvascular damage). A combination of prospective cohort, case-cohort, cross-sectional and case-control studydesigns will be employed to address these Specific Aims in the most efficient manner. In addition toinvestigating these novel research questions, as in the previous funding period, the HEALS will continue tosupport other biomedical research projects (including Projects 1 and 4 of the proposed program). This willbe the first prospective cohort study using individual level data on As exposure and metabolism, and findingsfrom this study will be directly relevant for both research and policy issues pertaining to the health of millionsof people around the world.
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