GSTM1, GSTT1, and GSTP1 genotypes in relation to breast cancer risk and frequency of mutations in the p53 gene

The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the GSTM1 and GSTT1 genes a nd an A-G polymorphism in the GSTP1 gene were investigated in relation to b reast cancer risk in 500 breast cancer patients and 395 controls. The effec ts of the GST genotypes on the frequency and pattern of p53 mutations in 38 8 breast carcinomas were also studied. A suggestive trend of increasing ris k of breast cancer with increasing number of G alleles of the GSTP1 was obs erved (P for trend, 0.11). The GSTM1 and GSTT1 polymorphisms did not show a n association with breast cancer. No increase in risk was observed with a c ombination of genotypes. A statistically significant association was observ ed between the GSTT1 genotype and p53 mutation status of the tumors, with p atients carrying the GSTT1 null genotype more frequently having mutations i n the p53 gene compared with patients with a GSTT1 gene present (24.6% vers us 12.4%; P = 0.019). There was also a suggestive trend for the GG genotype of the GSTP1 gene, but it was not statistically significant (P = 0.19). No association was observed with the type or location of mutations. We conclu de that the GSTP1 and GSTT1 genes could play a role in carcinogenesis in th e breast, possibly through increased frequency of mutations in tumor suppre ssor genes such as p53.