Breast cancer: role of polymorphisms in biotransformation enzymes

Eur J Hum Genet. 2004 Oct;12(10):848-54. doi: 10.1038/sj.ejhg.5201249.

Abstract

We aimed at determining whether any association exists between genetic polymorphisms in epoxide hydrolase (EPHX1), NADPH-quinone oxidoreductase (NQO1), glutathione S-transferases (GSTM1/P1/T1) and individual susceptibility to breast cancer. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in EPHX1 (exons 3 and 4), NQO1 (exon 6), GSTM1 (deletion), GSTP1 (exon 5), and GSTT1 (deletion) in a case-control study comprised of 238 patients with breast cancer and 313 healthy individuals. The distribution of genotypes in exon 6 of NQO1 was significantly different between the control group and breast cancer cases. Age-adjusted odds ratio (OR) for variant genotype NQO1*2/*2 was 3.68 (confidence interval (CI) = 1.41-9.62, P = 0.008). Association of GSTP1*2/*2 genotype as well as that of low EPHX1 activity deduced by combinations of genotypes in exons 3 and 4 with breast cancer was suggestive, but nonsignificant. Individuals simultaneously lacking GSTM1 and carrying at least one GSTP1 variant allele were at significantly higher risk of breast cancer (OR = 2.03, CI = 1.18-3.50, P = 0.010). Combinations of either GSTM1null or GSTP1*2 with low activity of EPHX1 presented significant risk of breast cancer (OR = 1.88, CI = 1.00-3.52, P = 0.049 and OR = 2.40, CI = 1.15-5.00, P = 0.019, respectively) as well. In conclusion, the results suggest that genetic polymorphisms in biotransformation enzymes may play a significant role in the development of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotransformation / genetics
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Epoxide Hydrolases / genetics*
  • Female
  • Glutathione Transferase / genetics*
  • Humans
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • Polymorphism, Genetic*

Substances

  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Glutathione Transferase
  • Epoxide Hydrolases