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Glutathione-S-transferase (GSTM1) Genetic Polymorphisms Do Not Affect Human Breast Cancer Risk, Regardless of Dietary Antioxidants

Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR 72079; ^a Department of Social & Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214; and ^b Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892

Glutathione-S-transferases catalyze the detoxication of carcinogen metabolites and reactive oxygen species (ROS) produced through a number of mechanisms. Glutathione-S-transferase (GST) M1 is polymorphic, and the null allele results in a lack of enzyme activity. Because there are indications that ROS may be involved in breast carcinogenesis, we sought to determine whether the GSTM1 null allele was associated with increased breast cancer, particularly among women with lower consumption of dietary sources of -tocopherol, carotenoids and ascorbic acid. In a study of diet and cancer in western New York, women with primary, incident, histologically confirmed breast cancer (n = 740) and community controls (n = 810) were interviewed and an extensive food-frequency questionnaire administered. A subset of these women provided a blood specimen. DNA was extracted and genotyping performed for GSTM1. Data were available for 279 cases and 340 controls. The null allele did not increase breast cancer risk, regardless of menopausal status. There were also no differences in associations between the polymorphism and risk among lower and higher consumers of dietary sources of antioxidants or smokers and nonsmokers. These results indicate that GSTM1 genetic polymorphisms are not associated with breast cancer risk, even in an environment low in antioxidant defenses.

KEY WORDS: • breast neoplasms • epidemiology/molecular • glutathione-S-transferase • oxidative stress • antioxidants

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