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Justenhoven, Ch.* ; Vollmert, C. ; Illig, T.

One-Carbon Metabolism and Breast Cancer Risk: No Association of MTHFR, MTR and TYMS - Polymorphisms in the GENICA Study from Germany.

Cancer Epidemiol. Biomarkers Prev. 14, 3015-3018 (2005)

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Open Access Green as soon as Postprint is submitted to ZB.

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Neoplastic development and growth are suspected to be influenced by availability and metabolism of folate due to effects on gene expression through DNA methylation and on genome integrity through DNA synthesis and repair (1-3). Key enzymatic regulators are methylene-tetrahydrofolate reductase (MTHFR) reducing 5,10-methylene-tetrahydrofolate to 5-methyl-tetrahydrofolate, the plasma form of folate and carbon donor for the remethylation of homocysteine to methionine (4), the methionine synthase (MTR) catalyzing methylation towards S-adenosyl-methionine (4), and thymidylate synthase (TYMS) catalyzing both the conversion of 5,10-methylene-tetrahydrofolate to dihydrofolate and of deoxyuridylate to deoxythymidylate, a rate-limiting nucleotide of DNA synthesis (5). Common variants MTHFR_677_C>T Ala²²²Val and MTHFR_1298_A>C Glu⁴²⁹Ala are associated with reduced in vitro enzyme activity (6-8), thereby increasing the availability of folate for thymidylate and purine synthesis, affect mRNA level in case of the TYMS_1494_del (TAAAGT) polymorphism (9), or are thought to affect the enzymatic activity and induce modest homocysteine reduction and DNA hypomethylation in case of the MTR_2756_A>G Asp⁹¹⁹Gly polymorphism (10-12). Although MTHFR variants are associated with a decreased risk for colon cancer (13), conflicting data on their association with breast cancer exist (14-25). For this reason, we investigated MTHFR, MTR, and TYMS polymorphisms in a population-based breast cancer case-control study (GENICA) from Germany for their potential role in breast cancer risk.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

ISSN (print) / ISBN 1055-9965

e-ISSN 1538-7755

Journal Cancer Epidemiology, Biomarkers & Prevention

Quellenangaben Volume: 14, Pages: 3015-3018

Publisher American Association for Cancer Research (AACR)

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology (EPI)