Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility

Background: The enzymes encoded by the glutathione S-transferase mu 1 (GSTM 1) and theta 1 (GSTT1) genes are involved in the metabolism (mainly inactiv ation, but activation is possible) of a wide range of carcinogens that are ubiquitous in the environment; the enzyme encoded by the GSTT1 gene may als o be active in endogenous mutagenic processes. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found in the population and result in a lack of enzyme activity. This study was undertaken to evaluate the associat ion between GSTM1 and GSTT1 gene polymorphisms and breast cancer risk. Meth ods: Our study included 466 women with incident cases of breast cancer occu rring from May 1989 through May 1994 and 466 matched control subjects. Thes e individuals were part of a prospective cohort of U.S. women (i.e., the Nu rses' Health Study). Odds ratios (ORs) and 95% confidence intervals (CIs) f rom conditional logistic regression models were used to estimate the associ ation between genetic polymorphisms and breast cancer risk. Results: The GS TM1 and GSTT1 null genotypes were not associated with an increased risk of breast cancer (OR = 1.05 [95% CI = 0.80-1.37] for GSTM1 null; OR = 0.86 [95 % CI = 0.61-1.21] for GSTT1 null). On the contrary, a suggestion of a decre ased risk of breast cancer associated with the GSTT1 null genotype was obse rved among premenopausal women. When considered together, no combination of the GSTM1 and GSTT1 genotypes was associated with an increased risk of bre ast cancer. The relationship between GSTM1 and GSTT1 gene deletions and bre ast cancer risk was not substantially modified by cigarette smoking. Conclu sions: Our data provide evidence against a substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions.