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Glutathione S-Transferase M1, M3, P1, and T1 Genetic Polymorphisms and Susceptibility to Breast Cancer¹

Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, 00250 Helsinki, Finland [K. M., A. H.]; Unit of Cancer Epidemiology (INSERM U521), Gustave-Roussy Institute, 54805 Villejuif, France [N. J., S. B.]; Departments of Oncology [V. K.], and Surgery [M. E.], Kuopio University Hospital, 70211 Kuopio, Finland; Departments of Clinical Pathology and Forensic Medicine [V-M. K.], and Clinical Nutrition [M. U.], University of Kuopio, 70211 Kuopio, Finland; and International Agency for Research on Cancer, 69372 Lyon, France [H. V.]

This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03–2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/Ile genotype (OR, 2.07; 95% CI, 1.02–4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10–90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99–15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations.

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