Cm. Maugard et al., Genetic polymorphism at the glutathione S-tranferase (GST) P1 locus is a breast cancer risk modifier, INT J CANC, 91(3), 2001, pp. 334-339
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.