Genetic polymorphism at the glutathione S-tranferase (GST) P1 locus is a breast cancer risk modifier

The isolation of full-length cDNAs of naturally occurring GSTP1 gene varian ts, and the demonstration that these alleles are distributed in the normal population, have provided conclusive evidence that the human GSTP1 gene loc us is polymorphic and that specific GSTP1 alleles may be associated with di fferent risk for cancers or other diseases. Recent data have indicated that the different GSTP1 alleles encode proteins with different enzymatic activ ities against carcinogens. In this case-control study, we examined the effe ct of the GSTP1 genetic polymorphism and its interaction with other factors to determine breast cancer risk. GSTP1 and GSTM1 genotypes of 220 breast c ancer patients and 196 controls, all residents of western France, were exam ined. Data on menopausal status and family cancer history were obtained fro m 195 patients and 147 controls. Exons 5 and 6 of the GSTP1 gene, which con tain the polymorphic nucleotide transitions, were analyzed by DNA polymeras e chain reaction-restriction fragment length polymorphism to distinguish be tween the GSTP1 alleles. In the control population, GSTP1 allelic frequenci es were 64.3%, 26.0% and 9.7%, respectively, for GSTP1*A, GSTP1*B and GSTP1 *C. In the breast cancer patients, the frequencies were 67.9% for GSTP1*A, 26.8% for GSTP1*B and 5.3% for GSTP1*C. In multivariate analysis, breast ca ncer risk increased by 7.7-fold (p < 0.001) in women with a family history of cancers and 2.18-fold (p = 0.026) in non-GSTP1*C individuals. GSTM1 geno types did not emerge as risk factor. Our results show that in addition to w ell-known risk factors, in particular, a family history of cancer. GSTP1 al lelopolymorphism is a significant modifier of breast cancer risk. The resul ts also suggest a protective role against breast cancer for the GSTP1*C all ele. (C) 2001 Wiley-Liss, Inc.