Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case-control study

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  • Beebe-Dimmer, Jennifer L
    • Other Affiliation: Program of Population Studies and Disparities Research, Karmanos Cancer Institute
  • Iyer, Priyanka T
    • Other Affiliation: Program of Population Studies and Disparities Research, Karmanos Cancer Institute
  • Nriagu, Jerome O
    • Other Affiliation: Department of Environmental Health Sciences and Epidemiology, University of Michigan
  • Keele, Greg R
    • Other Affiliation: Program of Population Studies and Disparities Research, Karmanos Cancer Institute
  • Mehta, Shilpin
    • Other Affiliation: Department of Oncology, Wayne State University
  • Meliker, Jaymie R
    • Other Affiliation: Department of Preventive Medicine and Graduate Program in Public Health, StonyBrook University Medical Center
  • Lange, Ethan
    • Affiliation: School of Medicine, Department of Genetics
  • Schwartz, Ann G
    • Other Affiliation: Program of Population Studies and Disparities Research, Karmanos Cancer Institute
  • Zuhlke, Kimberly A
    • Other Affiliation: Department of Internal Medicine, University of Michigan Medical School
  • Schottenfeld, David
    • Other Affiliation: Department of Epidemiology, University of Michigan
  • Cooney, Kathleen A
    • Other Affiliation: Department of Internal Medicine, University of Michigan Medical School
Abstract
  • Background Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. Methods Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate (<50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. Results While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). Conclusions Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.
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Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Jennifer L Beebe-Dimmer et al.; licensee BioMed Central Ltd.
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Journal title
  • Environmental Health
Journal volume
  • 11
Journal issue
  • 1
Page start
  • 43
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1476-069X
Bibliographic citation
  • Environmental Health. 2012 Jun 29;11(1):43
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • October 5, 2012

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file details 1476-069X-11-43.pdf 2019-05-07 Public Download
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file details Table S1. Pairwise linkage disequilibrium analysis of 5 selected single nucleotide polymorphisms in As3MT among participants of University of Michigan Bladder Cancer Study. 2019-05-07 Public Download