GLUTATHIONE S-TRANSFERASE M1 AND T1 NULL GENOTYPES, AND RISK OF BREAST CANCER

Background – Several studies have shown that the null genotypes of glutathione Stransferase M1 (GSTM1) and T1 (GSTT1) predispose to the development of specific types of cancers. A case-control study was carried out to examine the relationship between genetic polymorphisms of GSTM1 and GSTT1, and breast cancer risk. Methods – Blood samples from 57 females with breast cancer and 57 age- and sex-matched healthy individuals were collected. The eligible cases were randomly-selected patients at the Chemotherapy Unit of Nemazi Hospital, Shiraz, South of Iran from October 1999 to August 2000. Both patient and control groups were unrelated Iranian Muslims. Using polymerase chain reaction (PCR) method, the GSTM1 and GSTT1 genotypes were determined. The association between GSTM1 and GSTT1 genotypes, and the development of breast cancer was examined using odds ratio (OR) and 95% confidence intervals (CIs) derived from logistic regression analysis using SPSS 10.0 software (SPSS Inc, Chicago, IL, USA). Results – Homozygote deletion of either GSTM1 (OR = 1.65, 95% CI: 0.77 – 3.53) or GSTT1 (OR = 2.07, 95% CI: 0.96 – 4.48) was not associated with a statistically significant increased risk of breast cancer, whereas deletion of both GSTM1 and GSTT1 genes gave rise to a statistically significant increased risk of this malignancy (OR = 4.50, 95% CI: 1.30 – 15.58). Our results revealed that the combined genotypes were highly associated with breast cancer in the less than 50-year-old patients (OR = 5.63, 95% CI: 1.32 – 24.05). Conclusion – Our findings suggest a novel additive effect of GSTM1 and GSTT1 polymorphisms which plays an important role in susceptibility to breast cancer.