%0 Journal Article
%T Folate Intake, MTHFR Polymorphisms, and the Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis
%A Deborah A. Kennedy
%A Seth J. Stern
%A Ilan Matok
%A Myla E. Moretti
%A Moumita Sarkar
%A Thomasin Adams-Webber
%A Gideon Koren
%J Journal of Cancer Epidemiology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/952508
%X Background. The objective was to determine whether relationships exist between the methylene-tetrahydrofolate reductase (MTHFR) polymorphisms and risk of colorectal cancer (CRC) and examine whether the risk is modified by level of folate intake. Methods. MEDLINE, Embase, and SCOPUS were searched to May 2012 using the terms ※folic acid,§ ※folate,§ ※colorectal cancer,§ ※methylenetetrahydrofolate reductase,§ ※MTHFR.§ Observational studies were included which (1) assessed the risk of CRC for each polymorphism and/or (2) had defined levels of folate intake for each polymorphism and assessed the risk of CRC. Results. From 910 references, 67 studies met our criteria; hand searching yielded 10 studies. The summary risk estimate comparing the 677CT versus CC genotype was 1.02 (95% CI 0.95每1.10) and for 677TT versus CC was 0.88 (95% CI 0.80每0.96) both with heterogeneity. The summary risk estimates for A1298C polymorphisms suggested no reduced risk. The summary risk estimate for high versus low total folate for the 677CC genotype was 0.70 (95% CI 0.56每0.89) and the 677TT genotype 0.63 (95% CI 0.41每0.97). Conclusion. These results suggest that the 677TT genotype is associated with a reduced risk of developing CRC, under conditions of high total folate intake, and this associated risk remains reduced for both MTHFR 677 CC and TT genotypes. 1. Introduction Worldwide, colorectal cancer (CRC) is the third most frequently diagnosed cancer in males and the second in females [1]. Australia and New Zealand, Europe and North America have the highest incidence rates of CRC worldwide, and Africa and South-Central Asia, the lowest [1, 2]. Over 75% of CRCs occur sporadically, with only 25% of patients having a family history of CRC [3]. Folate insufficiency has been suggested as one of the possible mechanism for CRC development and progression. DNA strand breaks, impaired DNA methylation and repair have been associated with folate deficiency and CRC [4每7]. There are many enzymes involved with folates and one-carbon metabolism; however, the methylene tetrahydrofolate reductase (MTHFR) enzyme is a key enzyme responsible for determining whether reduced folates are directed towards DNA methylation pathways or pyrimidine or purine synthesis [8]. In 1995, a variant of MTHFR enzyme was identified which causes a substitution of C to T at nucleotide 677 [9]. The MTHFR C677T homozygous variant (TT genotype) is thermolabile, and its activity is reduced by 70% compared to the wild type (CC genotype) [10]. This reduced enzyme activity causes an accumulation of plasma homocysteine and higher
%U http://www.hindawi.com/journals/jce/2012/952508/