Open AccessJournal Article
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,Christine B. Ambrosone +10 more
TLDR
The association of risk with at least one low-activity COMT(Met) allele was strongest among the heaviest premenopausal women and among the leanest post menopausal women, suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.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 ( 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.read more
Citations
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Multifactor-Dimensionality Reduction Reveals High-Order Interactions among Estrogen-Metabolism Genes in Sporadic Breast Cancer
Marylyn D. Ritchie,Lance W. Hahn,Nady Roodi,L. Renee Bailey,William D. Dupont,Fritz F. Parl,Jason H. Moore +6 more
TL;DR: In this article, the authors introduced multifactor dimensionality reduction (MDR) as a method for reducing the dimensionality of multilocus information, to improve the identification of polymorphism combinations associated with disease risk.
Journal Article
Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors.
Pekka T. Männistö,Seppo Kaakkola +1 more
TL;DR: The enzyme responsible for the O- methylation, catechol- O -methyltransferase (COMT) was partly purified and characterized by the same group as EC, which first described the enzyme-catalyzed O-methylation of catechlamines and other catechols in the late 1950s.
Journal Article
A Systematic Review Of Genetic Polymorphisms and Breast Cancer Risk
Alison M. Dunning,Catherine S. Healey,Paul D.P. Pharoah,Teare,B. A. J. Ponder,Douglas F. Easton +5 more
TL;DR: Precise estimation of the risks associated with these and other as yet untested genes, as well as investigation of more complex risks arising from gene-gene and gene-environment interactions, will require much larger studies.
Journal ArticleDOI
Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase.
TL;DR: Experimental strategies used to study methylation pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic, molecular, and genomic approaches that have been used to determine the role of inheritance in variation in drug metabolism, effect, and toxicity.
Journal ArticleDOI
Chapter 3: Endogenous Estrogens as Carcinogens Through Metabolic Activation
TL;DR: Evidence shows that the catechols themselves are signaling molecules that work through the estrogen receptor that give rise to reactive quinones capable of forming direct adducts with glutathione and purines in DNA and of redox cycling to generate reactive oxygen species that can cause oxidative damage.
References
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Journal ArticleDOI
Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders.
Herbert M. Lachman,Demitri F. Papolos,Takuya Saito,Yue Min Yu,Carol L. Szumlanski,Richard M. Weinshilboum +5 more
TL;DR: The identification of a gentic marker associated with significant alterations in enzyme activity will facilitate the analysis of a possible role for the COMT gene in neuropsychiatric conditions in which abnormalities in catecholamine neurotransmission are believed to occur.
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Bao Ting Zhu,Allan H. Conney +1 more
TL;DR: Some of the many actions of estradiol may not be caused by est radiol per se, but may result from the formation of active estrogen metabolite(s) which function as local mediators or may activate their own unique receptors or effectors.
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Molecular origin of cancer: Catechol estrogen-3,4-quinones as endogenous tumor initiators
Ercole L. Cavalieri,Douglas E. Stack,Prabu Devanesan,Rosa Todorovic,I. Dwivedy,Sheila Higginbotham,S. L. Johansson,K. Patil,Michael L. Gross,J. K. Gooden,Ragulan Ramanathan,Ronald L. Cerny,Eleanor G. Rogan +12 more
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Molecular Mechanisms of Estrogen Carcinogenesis
James D. Yager,J G Liehr +1 more
TL;DR: The examples demonstrate that the parent compounds and their metabolites cause both nongenotoxic cell proliferative effects as well as direct and indirect genotoxic effects, which illustrates the complex nature of estrogen carcinogenesis.
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