# Arsenic and the Human Genome:  susceptibility and response to exposure  Supplement 3

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2022 · $56,610

## Abstract

SUMMARY
Inorganic arsenic (iAs) is a human carcinogen, and exposure to iAs affects >200 million individuals worldwide.
In Bangladesh, >57 million individuals (>25% of exposed individuals worldwide) are chronically exposed to iAs
through drinking-water from naturally contaminated wells that have some of the highest iAs concentrations
reported in the world. There is inter-individual variation in arsenic metabolism efficiency (AME) due to inherited
genetic variation, and this variability impacts individuals’ internal dose of arsenic and their toxicity risk.
Identifying genetic determinants of AME to help identify individuals at higher risk for toxicity has been a focus
within genetic epidemiology research. Previous studies have identified genetic variants in the AS3MT
(10q24.32) and FTCD (21q22.3) regions as showing clear association with AME. However, we currently know
of no other regions of the human genome that contain variants that show robust and replicable evidence of
association with AME, although studies of heritability suggest that additional variants are likely to exist. Our
first aim is to identify new regions that contain inherited genetic variation that affects individuals’ ability to
metabolize arsenic and their susceptibility to toxicity. We will achieve this aim by leveraging existing data from
>7,000 Bangladeshi participants from two studies of Bangladesh individuals with varying levels of exposure to
arsenic through drinking water: The Health Effects of Arsenic Longitudinal Study (HEALS) and the Bangladesh
Vitamin E and Selenium Trial (BEST). Our second aim is to assess the impact of returning personal genetic
information on susceptibility to arsenic toxicity to participants in rural Bangladesh. Using existing participant
data on inherited genetic variation known to impact AME and risk for arsenic toxicities, we will examine the
impact of returning of genetic information on arsenic susceptibility on subsequent behavioral changes related
to arsenic exposure reduction within HEALS. Returning genetic results to research participants is timely as we
are now aware of specific genetic risk factors that have a clear impact on arsenic toxicity risk. The proposed
work will make significant contributions to knowledge of genetic and environmental susceptibility to cancer and
will inform potential prevention strategies. We hope to identify novel inherited variants that impact susceptibility
to arsenic exposure. We will test the feasibility and benefits of returning genetic results to participants in a
rural, low resource setting, an intervention that, if successful, could be expanded in this population to reduce
exposure and prevent cancer. The training activities described in this proposal will build critical expertise in
genetic epidemiology, environmental health, and intervention research, and prepare the trainee for a career
focused on generating knowledge of genetic and environmental risk factors and applying genetic technologies
to impro...

## Key facts

- **NIH application ID:** 10479449
- **Project number:** 3R35ES028379-05S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Brandon Lee Pierce
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $56,610
- **Award type:** 3
- **Project period:** 2022-01-07 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479449

## Citation

> US National Institutes of Health, RePORTER application 10479449, Arsenic and the Human Genome:  susceptibility and response to exposure  Supplement 3 (3R35ES028379-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10479449. Licensed CC0.

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