Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer.

Abstract

Background: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer. Methods: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22–3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95%CI = 1.34–4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77–5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95% CI = 0.76–2.95). The risk of breast cancer increased as the number of putative highrisk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10–12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity). Conclusions: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.