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Genetic Polymorphisms in Catechol-O-Methyltransferase, Menopausal Status, and Breast Cancer Risk¹

Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas 72205 [P. A. T., A. S., F. F. K., C. B. A.]; Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892 [P. G. S.]; Department of Social & Preventive Medicine, State University of New York at Buffalo, Buffalo, New York 14214 [J. L. F., J. E. V., S. G., R. L., T. N.]; and Arizona Cancer Center, Tucson, Arizona 85724 [J. R. M.]

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols. In a case-control study, we evaluated the association of the low-activity allele (COMT^Met) with breast cancer risk. Compared to women with COMT^Val/Val, COMT^Met/Met was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4–4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2–0.7). The association of risk with at least one low-activity COMT^Met allele was strongest among the heaviest premenopausal women (OR, 5.7; CI, 1.1–30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1–0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.

¹ This work was a collaborative effort by the Division of Molecular Epidemiology, National Center for Toxicological Research, the Department of Social and Preventive Medicine, State University of New York at Buffalo, and the Laboratory of Human Carcinogenesis, National Cancer Institute. This work was supported, in part, by Grants CA11535, CA/ES62995, and CA01633 from the National Cancer Institute and the National Institute for Environmental Health Sciences and USAMRMC#CAMC17-94-J-4108. This work is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute.

² To whom requests for reprints should be addressed, at Division of Molecular Epidemiology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079. E-mail:cambrosone@nctr.fda.gov.

Received 11/24/97. Accepted 3/19/98.

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