Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis

Abstract

To clarify the influence of MTHFR C677T and A1298C polymorphisms on gastric cancer (GC), a meta-analysis of eight case-control studies (1,584/2,785 cases/controls) was carried out. Overall, there was moderate heterogeneity among studies, and the C677T allele T was associated with a 27% increased risk of GC compared with C allele: the random effects (RE) OR (95% confidence interval in parenthesis) was significant [OR=1.27 (1.13-1.44)]. In East Asians, the association was significant: RE OR=1.28 (1.14-1.44), whereas, in Caucasians it was not significant. Regarding gastric cancer adenocarcinoma (GCA), an association for the allele contrast in East Asians was detected: fixed effects (FE) OR=1.36 (1.18-1.56). The recessive model for allele T produced significant results overall and in East Asians for GC ) and FE OR=1.61 (1.32-1.96), respectively] and for GCA [RE OR=1.53 (1.13-2.05) and FE OR=1.70 (1.36-2.12)]. The A1298C polymorphism was associated with GCA in East Asians: the FE OR for the allele contrast (C vs. A) was 1.38 (1.18-1.62), and under a recessive model for allele C, OR=1.62 (1.28-2.06). There were no sources of bias in the selected studies; the differential magnitude of effect in large versus small studies was not significant. In conclusion, there is evidence of association between MTHFR polymorphisms and GC, mainly in East Asians.

The Association of Gastric Cancer Risk with Plasma Folate, Cobalamin, and Methylenetetrahydrofolate Reductase Polymorphisms in the European Prospective Investigation into Cancer and Nutrition

“…The number of studies of gastric cancer and the 1298 A!C SNP was limited and allowed only to estimate its role in East Asian populations where it was observed to be a risk factor for gastric cancer. Thus, a null result for the 677 C!T SNP in our study of Europeans combined with a suggestion of an effect of the variant 1298 genotype on gastric cancer risk agrees well with the meta-analysis (34). Furthermore, we did not observe any evidence of effect modification by folate status on the MTHFR-cancer relationship as has been observed with colorectal cancer (63).…”

“…The number of controls in our study was too small to show the weaker relationships between the 1298 A!C polymorphism and folate and tHcy (60). A recent meta-analysis of the two MTHFR polymorphisms and gastric cancer showed that the T allele and TT genotype of the 677 SNP is a strong risk factor in East Asian (particularly Chinese) populations (34). No such relationship was found in European or other populations.…”

“…Notably, a series of case-control studies have shown that the variant TT genotype is a strong risk factor for gastric cancer in Chinese (24)(25)(26)(27)(28), Italian (29), and Mexican (30) populations but not in Korean (31), German (32), or Polish (33) populations. A meta-analysis recently summarized these studies and concluded that the relationship between MTHFR 677 C!T polymorphism and gastric cancer was present in East Asian but not in the other studied populations (34).…”

Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis

“…Folate deficiency has been shown to induce DNA damage through uracil misincorporation into DNA during replication, leading to an increased risk of DNA doublestrand breaks during DNA excision repair and subsequent genetic instability (Blount et al 1997). MTHFR C677T and A1298C are two common polymorphisms that have been described for this enzyme (Frosst et al 1995;Weisberg et al 1998) and these have been associated with different disorders/ diseases Zintzaras 2006aZintzaras , 2006bZintzaras , 2006c. MTRR maintains the methionine synthase enzyme at an active stage for the remethylation of homocysteine to methionine (Hobbs et al 2000).…”

APOE gene polymorphisms and response to statin therapy

“…39 A differential magnitude of effect in large versus small studies was checked using the Egger regression test 40 and the Begg-Mazumdar test, which is based on Kendall's tau. 41 Given that these tests are underpowered, a differential magnitude of effect in large versus small studies were considered statistically significant at Po0.10.…”