title: Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Bailey
authors.forename: Allan H
authors.initials: AH
authors.lastname: Smith
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Tokar
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.forename: Kyoung-Woong
authors.initials: KW
authors.lastname: Kim
authors.forename: Panida
authors.initials: P
authors.lastname: Navasumrit
authors.forename: Mathuros
authors.initials: M
authors.lastname: Ruchirawat
authors.forename: Apinya
authors.initials: A
authors.lastname: Thiantanawat
authors.forename: William A
authors.initials: WA
authors.lastname: Suk
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D060766:Drinking Water / Q000032:analysis; D004781:Environmental Exposure; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced*; D012307:Risk Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D055815:Young Adult
chemical_list: D060766:Drinking Water; D014874:Water Pollutants, Chemical; D001151:Arsenic