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Carcinogenesis

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

Patricia A. Thompson, Peter G. Shields, Jo L. Freudenheim, Angie Stone, John E. Vena, James R. Marshall, Saxon Graham, Rosemary Laughlin, Takuma Nemoto, Fred F. Kadlubar and Christine B. Ambrosone
Patricia A. Thompson
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Peter G. Shields
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Jo L. Freudenheim
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Angie Stone
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John E. Vena
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James R. Marshall
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Saxon Graham
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Rosemary Laughlin
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Takuma Nemoto
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Fred F. Kadlubar
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Christine B. Ambrosone
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DOI:  Published May 1998
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Abstract

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 (COMTMet) with breast cancer risk. Compared to women with COMTVal/Val, COMTMet/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 COMTMet 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.

Footnotes

  • ↵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 November 24, 1997.
  • Accepted March 19, 1998.
  • ©1998 American Association for Cancer Research.
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May 1998
Volume 58, Issue 10
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Genetic Polymorphisms in Catechol-O-Methyltransferase, Menopausal Status, and Breast Cancer Risk
Patricia A. Thompson, Peter G. Shields, Jo L. Freudenheim, Angie Stone, John E. Vena, James R. Marshall, Saxon Graham, Rosemary Laughlin, Takuma Nemoto, Fred F. Kadlubar and Christine B. Ambrosone
Cancer Res May 15 1998 (58) (10) 2107-2110;

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Genetic Polymorphisms in Catechol-O-Methyltransferase, Menopausal Status, and Breast Cancer Risk
Patricia A. Thompson, Peter G. Shields, Jo L. Freudenheim, Angie Stone, John E. Vena, James R. Marshall, Saxon Graham, Rosemary Laughlin, Takuma Nemoto, Fred F. Kadlubar and Christine B. Ambrosone
Cancer Res May 15 1998 (58) (10) 2107-2110;
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