Background: Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer.

Objectives: This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure.

Discussion: Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects.

Conclusions: Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes.

Citation: Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360

Address correspondence to R.C. Fry, Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, 135 Dauer Dr., CB 7431, University of North Carolina, Chapel Hill, NC 27599-7295 USA. Telephone: (919) 843-6864. E-mail: rfry@unc.edu

This research was supported by grants from the National Institute of Environmental Health Sciences (P30-ES010126, P42-ES005948, R01-ES019315, T32-ES07018, and P42-ES04705).

The authors declare they have no actual or potential competing financial interests.

Received: 17 October 2014 Accepted: 23 June 2015 Advance Publication: 26 June 2015 Final Publication: 1 February 2016

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