The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer

Abstract

Polymorphisms in genes involved in folate metabolism may modulate the risk of colorectal cancer (CRC), but data from published studies are conflicting. The current meta-analysis was performed to address a more accurate estimation. A total of 41 (17,552 cases and 26,238 controls), 24(8,263 cases and 12,033 controls), 12(3,758 cases and 5,646 controls), and 13 (5,511 cases and 7,265 controls) studies were finally included for the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1289C, methione synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G polymorphisms and the risk of CRC, respectively. The data showed that the MTHFR 677T allele was significantly associated with reduced risk of CRC (OR = 0.93, 95%CI 0.90-0.96), while the MTRR 66G allele was significantly associated with increased risk of CRC (OR = 1.11, 95%CI 1.01-1.18). Sub-group analysis by ethnicity revealed that MTHFR C677T polymorphism was significantly associated with reduced risk of CRC in Asians (OR = 0.80, 95%CI 0.72-0.89) and Caucasians (OR = 0.84, 95%CI 0.76-0.93) in recessive genetic model, while the MTRR 66GG genotype was found to significantly increase the risk of CRC in Caucasians (GG vs. AA: OR = 1.18, 95%CI 1.03-1.36). No significant association was found between MTHFR A1298C and MTR A2756G polymorphisms and the risk of CRC. Cumulative meta-analysis showed no particular time trend existed in the summary estimate. Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test. Collectively, this meta-analysis suggested that MTHFR 677T allele might provide protection against CRC in worldwide populations, while MTRR 66G allele might increase the risk of CRC in Caucasians. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.

Role of polymorphism of methyltetrahydrofolate-homocysteine methyltransferase (MTR) A2756G and breast cancer risk

“…De Also in many studies on other cancers, scientists cannot find a significant association, for example, Jackson et al, 2012 [26], in men 40-80 years old in a Jamaican population with prostate cancer and only serum folate was measured by an immunoassay method, Weiner et al, 2012 [27], with prostatic cancer in the Western Siberian Region of Russia, and Daijun Zhou et al, 2012, by meta-analysis [28], upon colorectal cancer (CRC) in Caucasians.…”

Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Colorectal Cancer among Jordanian Population

“…A marginal association was found in a meta-analysis of the allele and genotypes of MTHFR A1298C (C vs. A, CC vs. AA, and CC vs. CA+AA). The trend disappeared after exclusion of one study, in which the 95% CI did not overlap the lines of the pooled results (Zhou et al, 2012). A lack of association may be due to methodological reasons (e.g., non-population-based study, small sample size), or it may be that there is a relation that depends on the nutrient status of folate and/or related nutrients which we did not investigate.…”

“…Prior to our investigation, based on Zhou et al (2012) the studies that investigated MTHFR C677T were distributed by ethnicity as follows: 20 studies recruited Caucasians; 11 studies examined individuals of Asian descent; the remaining 10 studies were on Indians, Africans, Hawaiian, or mixed populations. There was a single study conducted in an Arab country which is Egypt (El Awady et al, 2009).…”

“…The genetic polymorphism of MTHFR seems to be related to the risk of CRC, but this may not hold true for all populations (Taioli et al, 2009;Zhou et al, 2012). The aim of this study was to determine if MTHFR C677T and A1298C polymorphism is/are associated with an altered risk of developing CRC among Jordanians.…”

“…A systematic review examined the association of genetic polymorphism at A1298C with CRC in 24 previously published studies (Zhou et al, 2012). In contrast to the significant association between MTHFR C677T and the risk of CRC, the MTHFR A1298C polymorphism was found to be not significantly related with the risk of CRC.…”