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. 2002 Jun;110(6):591–593. doi: 10.1289/ehp.02110591

GSTT1 and CYP2E1 polymorphisms and trihalomethanes in drinking water: effect on childhood leukemia.

Claire Infante-Rivard 1, Devendra Amre 1, Daniel Sinnett 1
PMCID: PMC1240875  PMID: 12055050

Abstract

The purpose of the study was to determine whether the risk of childhood acute lymphoblastic leukemia (ALL) associated with drinking water disinfection by-products was modified in the presence of variants in genes involved in the metabolism of trihalomethanes (THMs). We included a subset of cases from a population-based case-control study in a case-only study to estimate the interaction odds ratios (IORs) between prenatal and postnatal exposure to THMs and polymorphisms in the GSTT1 and CYP2E1 genes. We compared cases with and without a given variant regarding their exposure to THMs using unconditional logistic regression. The IOR for a postnatal average of total THM above the 95th percentile with GSTT1 null genotype was 9.1 [95% confidence interval (95% CI), 1.4-57.8]. With CYP2E1 (variant G-1259C, known as the allele CYP2E1*5), the effect of exposure during pregnancy for an average exposure to total THM at or above the 75th percentile was 9.7 (95% CI, 1.1-86.0). These results contrast strongly with those from our case-control analysis, in which we considered the exposure to THMs only in relation with ALL, and observed no increase in risk or very moderate ones. The present preliminary study shows suggestive but imprecise results. We found no similar results in the literature, underscoring the need for other studies as well as the potential usefulness of combining exposure and relevant genetic information in such studies.

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Selected References

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  1. Allis J. W., Brown B. L., Zhao G., Pegram R. A. The effects of inhalation exposure to bromo-dichloromethane on specific rat CYP isoenzymes. Toxicology. 2001 Mar 21;161(1-2):67–77. doi: 10.1016/s0300-483x(00)00461-3. [DOI] [PubMed] [Google Scholar]
  2. Constan A. A., Sprankle C. S., Peters J. M., Kedderis G. L., Everitt J. I., Wong B. A., Gonzalez F. L., Butterworth B. E. Metabolism of chloroform by cytochrome P450 2E1 is required for induction of toxicity in the liver, kidney, and nose of male mice. Toxicol Appl Pharmacol. 1999 Oct 15;160(2):120–126. doi: 10.1006/taap.1999.8756. [DOI] [PubMed] [Google Scholar]
  3. Fagliano J., Berry M., Bove F., Burke T. Drinking water contamination and the incidence of leukemia: an ecologic study. Am J Public Health. 1990 Oct;80(10):1209–1212. doi: 10.2105/ajph.80.10.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Foster A. M., Prentice A. G., Copplestone J. A., Cartwright R. A., Ricketts C. The distribution of leukaemia in association with domestic water quality in south west England. Eur J Cancer Prev. 1997 Feb;6(1):11–19. doi: 10.1097/00008469-199702000-00003. [DOI] [PubMed] [Google Scholar]
  5. Hayashi S., Watanabe J., Kawajiri K. Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem. 1991 Oct;110(4):559–565. doi: 10.1093/oxfordjournals.jbchem.a123619. [DOI] [PubMed] [Google Scholar]
  6. Hirvonen A. Polymorphisms of xenobiotic-metabolizing enzymes and susceptibility to cancer. Environ Health Perspect. 1999 Feb;107 (Suppl 1):37–47. doi: 10.1289/ehp.99107s137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Infante-Rivard C., Olson E., Jacques L., Ayotte P. Drinking water contaminants and childhood leukemia. Epidemiology. 2001 Jan;12(1):13–19. doi: 10.1097/00001648-200101000-00004. [DOI] [PubMed] [Google Scholar]
  8. Khoury M. J., Flanders W. D. Nontraditional epidemiologic approaches in the analysis of gene-environment interaction: case-control studies with no controls! Am J Epidemiol. 1996 Aug 1;144(3):207–213. doi: 10.1093/oxfordjournals.aje.a008915. [DOI] [PubMed] [Google Scholar]
  9. Krajinovic M., Labuda D., Richer C., Karimi S., Sinnett D. Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms. Blood. 1999 Mar 1;93(5):1496–1501. [PubMed] [Google Scholar]
  10. Mills C. J., Bull R. J., Cantor K. P., Reif J., Hrudey S. E., Huston P. Workshop report. Health risks of drinking water chlorination by-products: report of an expert working group. Chronic Dis Can. 1998;19(3):91–102. [PubMed] [Google Scholar]
  11. Pegram R. A., Andersen M. E., Warren S. H., Ross T. M., Claxton L. D. Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: contrasting results with bromodichloromethane off chloroform. Toxicol Appl Pharmacol. 1997 May;144(1):183–188. doi: 10.1006/taap.1997.8123. [DOI] [PubMed] [Google Scholar]
  12. Sinnett D., Krajinovic M., Labuda D. Genetic susceptibility to childhood acute lymphoblastic leukemia. Leuk Lymphoma. 2000 Aug;38(5-6):447–462. doi: 10.3109/10428190009059264. [DOI] [PubMed] [Google Scholar]
  13. Wacholder S., Rothman N., Caporaso N. Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias. J Natl Cancer Inst. 2000 Jul 19;92(14):1151–1158. doi: 10.1093/jnci/92.14.1151. [DOI] [PubMed] [Google Scholar]
  14. Weinberg C. R., Umbach D. M. Choosing a retrospective design to assess joint genetic and environmental contributions to risk. Am J Epidemiol. 2000 Aug 1;152(3):197–203. doi: 10.1093/aje/152.3.197. [DOI] [PubMed] [Google Scholar]

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