{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:23:52Z","timestamp":1770722632925,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,11,27]],"date-time":"2010-11-27T00:00:00Z","timestamp":1290816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Global DNA hypomethylation associates with development of cancer. DNA hypomethylation also associates with hyperhomocysteinemia and <jats:italic>MTHFR<\/jats:italic> c.677C&gt;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 <jats:italic>MTHFR<\/jats:italic> c.677TC&gt;T variant with hyperhomocysteinemia and with cancer. We performed a cross\u2010sectional 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\u2010analyses of 231 studies including 74,671 cases and 93,344 controls. Cross\u2010sectionally, plasma homocysteine levels were 12.9 and 11.6 \u03bcmol\/L in those with and without cancer (<jats:italic>p<\/jats:italic> &lt; 0.0001). However, homocysteine levels increased with age and age\u2010adjusted odds ratio for any cancer in those with homocysteine levels &gt;12.4 <jats:italic>versus<\/jats:italic> &lt; 9.4 \u03bcmol\/L did not differ from 1.0. In cancer\u2010free participants, plasma homocysteine levels were 14.7 and 11.7 \u03bcmol\/L in <jats:italic>MTHFR<\/jats:italic> c.677C&gt;T homozygtes and noncarriers (<jats:italic>p<\/jats:italic> &lt; 0.0001). Prospectively, hazard ratios for any cancer and for cancer subtypes in <jats:italic>MTHFR<\/jats:italic> c.677C&gt;T homozygotes <jats:italic>versus<\/jats:italic> noncarriers did not differ from 1.0. However, in meta\u2010analyses odds ratio for <jats:italic>MTHFR<\/jats:italic> c.677C&gt;T homozygotes <jats:italic>versus<\/jats:italic> noncarriers were 1.07 (95% CI: 1.01\u20131.12) for any cancer, 1.77 (1.17\u20132.68) for esophagus cancer, 1.40 (1.19\u20131.66) for gastric cancer and 0.85 (0.77\u20130.94) for colorectal cancer. Increased plasma homocysteine levels are not associated with an increased age\u2010adjusted risk of any cancer. However, <jats:italic>MTHFR<\/jats:italic> c.677C&gt;T homozygosity with lifelong hyperhomocysteinemia and hence hypomethylation associate with increased risk of esophagus and gastric cancer, and with decreased risk of colorectal cancer.<\/jats:p>","DOI":"10.1002\/ijc.25375","type":"journal-article","created":{"date-parts":[[2010,4,5]],"date-time":"2010-04-05T14:52:42Z","timestamp":1270479162000},"page":"644-652","source":"Crossref","is-referenced-by-count":45,"title":["Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C&gt;T polymorphism and risk of cancer: Cross\u2010sectional and prospective studies and meta\u2010analyses of 75,000 cases and 93,000 controls"],"prefix":"10.1002","volume":"128","author":[{"given":"Jeppe","family":"Zacho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiva","family":"Yazdanyar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stig E.","family":"Bojesen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Tybj\u00e6rg\u2010Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00f8rge G.","family":"Nordestgaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,11,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-2863(98)00074-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2005.05.001"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023075"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/128.7.1204"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.8.2444S"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2257.2001.00370.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(94)90149-X"},{"key":"e_1_2_6_9_2","first-page":"23","volume-title":"Folate in health and in disease","author":"Wagner C","year":"1995"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-111"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1370"},{"key":"e_1_2_6_12_2","first-page":"5860","article-title":"The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase","volume":"9","author":"Kawakami K","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_13_2","first-page":"849","article-title":"Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene","volume":"9","author":"Stern LL","year":"2000","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062066299"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.328.7433.211"},{"key":"e_1_2_6_16_2","first-page":"1089","article-title":"The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro","volume":"10","author":"Crott JW","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3290"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00261686"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djg005"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.8367"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.3.299"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707402"},{"key":"e_1_2_6_23_2","first-page":"535","article-title":"The Danish Cancer Registry\u2014history, content, quality and use","volume":"44","author":"Storm HH","year":"1997","journal-title":"Dan Med Bull"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/17.1.44"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00350-1"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0897"},{"key":"e_1_2_6_27_2","first-page":"391","volume-title":"Competing risks survival analysis. 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