Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C>T polymorphism and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls

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Global DNA hypomethylation associates with development of cancer. DNA hypomethylation also associates with hyperhomocysteinemia and MTHFR c.677C>T homozygosity, both of which may associate with increased risk of cancer. We tested the putative association of hyperhomocysteinemia with cancer and the association of the MTHFR c.677TC>T variant with hyperhomocysteinemia and with cancer. We performed a cross-sectional study of 5,949 Danish general population adults, a prospective study of 9,235 Danish general population adults with up to 60 years of registry surveillance, and meta-analyses of 231 studies including 74,671 cases and 93,344 controls. Cross-sectionally, plasma homocysteine levels were 12.9 and 11.6 µmol/L in those with and without cancer (p <0.0001). age age-adjusted and any cancer for homocysteine however, in increased levels odds ratio those with>12.4 versus <9.4 µmol 1.0. 11.7 14.7 and c.677c cancer-free did differ from homocysteine in l levels mthfr not participants, plasma were>T homozygtes and noncarriers (p <0.0001). and any c.677c cancer for hazard in mthfr prospectively, ratios subtypes>T homozygotes versus noncarriers did not differ from 1.0. However, in meta-analyses odds ratio for MTHFR c.677C>T homozygotes versus noncarriers were 1.07 (95% CI: 1.01-1.12) for any cancer, 1.77 (1.17-2.68) for esophagus cancer, 1.40 (1.19-1.66) for gastric cancer and 0.85 (0.77-0.94) for colorectal cancer. Increased plasma homocysteine levels are not associated with an increased age-adjusted risk of any cancer. However, MTHFR c.677C>T homozygosity with lifelong hyperhomocysteinemia and hence hypomethylation associate with increased risk of esophagus and gastric cancer, and with decreased risk of colorectal cancer.
Original languageEnglish
JournalInternational Journal of Cancer
Volume128
Issue number3
Pages (from-to)644-52
Number of pages9
ISSN0020-7136
DOIs
Publication statusPublished - 2011

ID: 40184948