SCOPE: 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-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTHFR, MTR, MTRR, CBS, TCNII, RFC, GCPII, SHMT, TYMS, and MTHFD1, including five meta-analyses on MTHFR 677C>T (rs1801133) and MTHFR 1298C>T (rs1801131); two meta-analyses on MTR-2756A>C (rs1805087); and one for MTRR 66A>G (rs1801394). METHODS AND RESULTS: This systematic review synthesizes these data, highlighting the consistent inverse association between MTHFR 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-analyses we observed some evidence for SHMT 1420C>T (rs1979277) ((odds ratio) OR = 0.85; 95% confidence interval (CI) = 0.73-1.00 for TT v. CC) and TYMS 5' 28 bp repeat (rs34743033) and CRC risk (OR = 0.84; 95% CI = 0.75-0.94 for 2R/3R v. 3R/3R and OR = 0.82; 95% CI = 0.69-0.98 for 2R/2R v. 3R/3R). CONCLUSION: To gain further insight into the role of folate variants in colorectal neoplasia will require incorporating measures of the metabolites, including B-vitamin cofactors, homocysteine and S-adenosylmethionine, and innovative statistical methods to better approximate the folate one-carbon metabolism pathway.
SCOPE: 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-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTHFR, MTR, MTRR, CBS, TCNII, RFC, GCPII, SHMT, TYMS, and MTHFD1, including five meta-analyses on MTHFR 677C>T (rs1801133) and MTHFR 1298C>T (rs1801131); two meta-analyses on MTR-2756A>C (rs1805087); and one for MTRR 66A>G (rs1801394). METHODS AND RESULTS: This systematic review synthesizes these data, highlighting the consistent inverse association between MTHFR 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-analyses we observed some evidence for SHMT 1420C>T (rs1979277) ((odds ratio) OR = 0.85; 95% confidence interval (CI) = 0.73-1.00 for TT v. CC) and TYMS 5' 28 bp repeat (rs34743033) and CRC risk (OR = 0.84; 95% CI = 0.75-0.94 for 2R/3R v. 3R/3R and OR = 0.82; 95% CI = 0.69-0.98 for 2R/2R v. 3R/3R). CONCLUSION: To gain further insight into the role of folate variants in colorectal neoplasia will require incorporating measures of the metabolites, including B-vitamin cofactors, homocysteine and S-adenosylmethionine, and innovative statistical methods to better approximate the folate one-carbon metabolism pathway.
Authors: Hui Lv; Shao-Yan Hu; Zhi-Zuo Du; Zong Zhai; Lan Cao; Yi-Na Sun; Jun Lu; Jie Li; Hai-Long He; Yi-Huan Chai; Yi Wang Journal: Int J Clin Exp Pathol Date: 2018-03-01
Authors: Ting-Yuan David Cheng; Karen W Makar; Marian L Neuhouser; Joshua W Miller; Xiaoling Song; Elissa C Brown; Shirley A A Beresford; Yingye Zheng; Elizabeth M Poole; Rachel L Galbraith; David J Duggan; Nina Habermann; Lynn B Bailey; David R Maneval; Marie A Caudill; Adetunji T Toriola; Ralph Green; Cornelia M Ulrich Journal: Cancer Date: 2015-06-24 Impact factor: 6.860
Authors: Jun Wang; Isaac Asante; John A Baron; Jane C Figueiredo; Robert Haile; A Joan Levine; Polly A Newcomb; Allyson S Templeton; Fredrick R Schumacher; Stan G Louie; Graham Casey; David V Conti Journal: Genet Epidemiol Date: 2019-09-10 Impact factor: 2.135
Authors: Julia Krushkal; Yingdong Zhao; Curtis Hose; Anne Monks; James H Doroshow; Richard Simon Journal: Clin Epigenetics Date: 2016-06-24 Impact factor: 6.551
Authors: Robin Myte; Björn Gylling; Jenny Häggström; Jörn Schneede; Anna Löfgren-Burström; Jeroen R Huyghe; Göran Hallmans; Klaus Meyer; Ingegerd Johansson; Per Magne Ueland; Richard Palmqvist; Bethany Van Guelpen Journal: PLoS One Date: 2018-04-25 Impact factor: 3.240