{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:59:31Z","timestamp":1791223171779,"version":"4.1.0"},"reference-count":109,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T00:00:00Z","timestamp":1360281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>The metabolism of folate involves a complex network of polymorphic enzymes that may explain a proportion of the risk associated with colorectal neoplasia. Over 60 observational studies primarily in non\u2010Hispanic White populations have been conducted on selected genetic variants in specific genes, <jats:italic>MTHFR<\/jats:italic>, <jats:italic>MTR<\/jats:italic>, <jats:italic>MTRR<\/jats:italic>, <jats:italic>CBS<\/jats:italic>, <jats:italic>TCNII<\/jats:italic>, <jats:italic>RFC<\/jats:italic>, <jats:italic>GCPII<\/jats:italic>, <jats:italic>SHMT<\/jats:italic>, <jats:italic>TYMS<\/jats:italic>, and <jats:italic>MTHFD1<\/jats:italic>, including five meta\u2010analyses on <jats:italic>MTHFR<\/jats:italic> 677C&gt;T (rs1801133) and <jats:italic>MTHFR<\/jats:italic> 1298C&gt;T (rs1801131); two meta\u2010analyses on <jats:italic>MTR<\/jats:italic>\u20102756A&gt;C (rs1805087); and one for <jats:italic>MTRR<\/jats:italic> 66A&gt;G (rs1801394).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>This systematic review synthesizes these data, highlighting the consistent inverse association between <jats:italic>MTHFR<\/jats:italic> 677TT genotype and risk of colorectal cancer (CRC) and its null association with adenoma risk. Results for other variants varied across individual studies; in our meta\u2010analyses we observed some evidence for <jats:italic>SHMT<\/jats:italic> 1420C&gt;T (rs1979277) ((odds ratio) OR = 0.85; 95% confidence interval (CI) = 0.73\u20131.00 for TT v. CC) and <jats:italic>TYMS<\/jats:italic> 5\u2019 28 bp repeat (rs34743033) and CRC risk (OR = 0.84; 95% CI = 0.75\u20130.94 for 2R\/3R v. 3R\/3R and OR = 0.82; 95% CI = 0.69\u20130.98 for 2R\/2R v. 3R\/3R).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To gain further insight into the role of folate variants in colorectal neoplasia will require incorporating measures of the metabolites, including B\u2010vitamin cofactors, homocysteine and <jats:italic>S<\/jats:italic>\u2010adenosylmethionine, and innovative statistical methods to better approximate the folate one\u2010carbon metabolism pathway.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201200278","type":"journal-article","created":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T08:55:04Z","timestamp":1360313704000},"page":"607-627","source":"Crossref","is-referenced-by-count":31,"title":["Folate\u2010genetics and colorectal neoplasia: What we know and need to know next"],"prefix":"10.1002","volume":"57","author":[{"given":"Jane C.","family":"Figueiredo","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine Keck School of Medicine University of Southern California  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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