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Supplement 1: Exploring the Relationship Between Arsenic and Cancer

Project Summary

Project Leader:
M. Elena Martinez, Ph.D.

Arsenic (As) in the environment exists in several oxidative and physical states, with a major source of exposure through drinking water. Arsenic is recognized as a human skin, bladder and lung carcinogen following either ingestion or inhalation.  Only limited attention has been paid to the effect of As on gastrointestinal cancers.  However, at least two studies have suggested an increased risk for colon cancer with elevated arsenic levels.  Arsenic concentrations are known to vary across geographical locations with higher levels found in the Western US, such as in Arizona, and northern Mexico. Arsenic is at best a weak mutagen and, at environmentally relevant doses, does not interact directly with DNA.  Several hypotheses exist concerning the mode(s) of action including inhibition of DNA repair, increased oxidative stress, inhibition of cell cycle checkpoint genes, alteration of DNA methylation and increased cell proliferation.  Furthermore, it has been suggested that As metabolism can be modified by genetic polymorphisms in As methylating enzymes.

We have assembled a binational team of investigators from Arizona and Sonora, Mexico who are experienced in arsenic research, exposure assessment, and cancer research. The overall goal of the project is to evaluate associations between elevated As exposure and selected genetic polymorphisms that are either considered to be part of carcinogenesis pathways or can potentially modulate As metabolism.  We propose two research perspectives. Phase 1 will focus on determining the effect of As and As metabolites on cell proliferation in colon cancer cell lines. Phase 2 is a pilot study to evaluate these associations in human populations living in Arizona and Mexico at varying background As exposure levels. We will determine exposure via modeled As exposure and speciated As urinary biomarkers (n=350). We will also evaluate gene polymorphisms potentially affected by As and how these genes modulate associations between modeled and urinary arsenic in these populations. This pilot study will increase the capacity of both Mexican and US investigators and provide preliminary data for future studies of the relationship between potential environmental exposures, such as arsenic, and cancer.

 

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