Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Gastric Cancer Risk: A Huge-GSEC Review

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640 controls for C677T and seven studies, 1,223 cases and 2,015 controls for A1298C; pooled analyses: nine studies, 1,540 cases and 2,577 controls for C677T and five studies, 1,146 cases and 1,549 controls for A1298C). An increased risk was found for MTHFR 677 TT in the meta-analysis (odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.31, 1.77) and pooled analysis (OR = 1.49, 95% CI: 1.14, 1.95). No association resulted for MTHFR 1298 CC (meta-OR = 0.94, 95% CI: 0.65, 1.35; pooled OR = 0.90, 95% CI: 0.69, 1.34). Results from the pooled analysis of four studies on C677T stratified according to folate levels showed an increased risk for individuals with low (OR = 2.05, 95% CI: 1.13, 3.72) versus high (OR = 0.95, 95% CI: 0.54, 1.67) folate levels. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis.

MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption

“…They were not different from those found in our control subjects and comparable to those reported previously in other European populations (Boccia et al, 2008). Furthermore, similar frequencies, always in equilibrium with the Hardy-Weinberg equation, were detected in patients with viral or alcoholic cirrhosis.…”

“…Not surprisingly, therefore, the relationship between MTHFR C677T SNP and the occurrence of malignant diseases has been explored in leukemia (Franco et al, 2001;Robien and Ulrich, 2003;Skibola et al, 1999), stomach (Boccia et al, 2008), colon (Ma et al, 1997;Sharp and Little, 2004;Slattery et al, 1999), breast (Beilby et al, 2004), and bladder (Lin et al, 2004) cancer. Two studies in patients with HCC have yielded conflicting results (Mu et al, 2007;Saffroy et al, 2004).…”

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

“…20 The potential associations between MTHFR genotype status and a number of medical complications have been evaluated using methodologies such as case-control, cohort, Mendelian randomization, and meta-analysis. A modest positive association has been found between the MTHFR "thermolabile" polymorphism and many different medical complications, including, but not limited to, thromboembolic disease (in non-North-American populations only), 21,22 stroke, [23][24][25][26][27] aneurysm, 28 peripheral artery disease, 29 migraine, 30 hypertension, 31,32 recurrent pregnancy loss, 33,34 male infertility, 35,36 risk for offspring with neural tube defects, 37,38 certain cancers, [39][40][41] neuropsychiatric disease, 42 and chemotherapy toxicity. 43,44 …”

MTHFR Gene Polymorphisms are Not Involved in Pancreatic Cancer Risk: A Meta-analysis

“…To our knowledge, this is the first meta-analysis considering MTHFR polymorphisms and the risk of pancreatic cancer.Previous meta-analyses have shown the MTHFR 677TT genotype increase gastric cancer risk (Boccia, 2008),the possible mechanism is 677T allele contributes to DNA hypomethylation,which in turn may lead to altered gene expression and the polymorphism decrease the risk of colorectal cancer (Botto, 2000;Kono, 2005;Sanjoaquin, 2005;Taioli, 2009). It may be due to C677T polymorphism exert a protective effect by increasing the levels of the MTHFR substrate (essential for DNA synthesis).…”