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Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk¹

Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, 00250 Helsinki, Finland [K. M., A. H.]; Unit of Cancer Epidemiology, 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; Department of Preventive Medicine, Seoul National University College of Medicine, Institute of Environmental Medicine, SNUMRC, Seoul 110-799, Korea [D. K.]; and International Agency for Research on Cancer, 69372 Lyon, France [H. V.]

We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol-O-methyltransferase (COMT) genotype in individual susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression after adjustment for known or suspected risk factors for breast cancer. When studied separately by menopausal status, the COMT-L allele-containing genotypes were inversely associated with premenopausal breast cancer, especially with advanced stage of the disease (OR, 0.44; 95% CI, 0.22–0.87). Among postmenopausal women a similar decreased risk was seen for local carcinoma associated with the COMT-LL genotype (OR, 0.55; 95% CI, 0.31–0.98). The lowest breast cancer risk was seen in the postmenopausal women with the COMT-LL genotype and low body-mass index (25.4 kg/m²; OR, 0.33; 95% CI, 0.13–0.83). Significantly increased risk, on the other hand, was seen for postmenopausal women with the COMT-LL genotype and long-term (>30 months) use of estrogen (OR, 4.02; 95% CI, 1.13–14.3), or with the COMT-L allele-containing genotypes and early age (12 years) at menarche (OR, 8.59; 95% CI, 1.85–39.8). Our study, therefore, suggests that the COMT genotype may define a portion of the individual breast cancer susceptibility that is associated with reproductive events and hormone exposure even if it does not seem to be a major overall risk factor for this malignancy.

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