Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer:: Results from the Shanghai breast cancer study and meta-analysis

Purpose: We studied the relation of breast cancer to common deletion mutations in GSTM1 and GSTT1 and the functional Ile(105)Val polymorphism in GSTP1 in a large, population-based case-control study conducted in China and performed a meta-analysis to summarize the literature. Experimental Design: In the case-control study, a total of 1144 breast cancer cases and 1221 community controls were genotyped for GSTM1, GSTP1, and GSTT1 using PCR-based methods. Associations of genotypes and breast cancer were evaluated in logistic regression models. Meta-analysis odds ratios (ORs) were estimated using a fixed effects model. Results: In the case-control study, associations were null for GSTM1 [age-adjusted OR 0.97, 95% confidence interval (Cl): 0.82-1.14] and GSTT1 (OR 0.97, 95% CI: 0.83-1.15). A significant increase in risk was observed among homozygotes for the variant Ile(105)Val polymorphism (OR 1.92, 95% CI: 1.21-3.04). No combined effects of GSTM1, GSTP1, and GSTT1 genotypes or interactions with potential effect modifiers were detected. All results were similar in pre- and postmenopausal women and for early versus advanced stage breast cancer. The meta-analysis, based predominately on Caucasian women, supported null results for the homozygous deletion variant in GSTM1 (summary OR 1.05; combining 19 studies) and GSTT1 (summary OR 1.11; 15 studies). Meta-analysis results for the homozygous; GSTP1 variant indicated no overall association (summary OR 1.04; 10 studies), although results varied significantly across studies (P = 0.009). Conclusions: This large case-control study provides strong support for earlier studies showing no overall association of the GSTM1 and GSTT1 deletion