Breast cancer: role of polymorphisms in biotransformation enzymes

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.