Abstract
Associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and esophageal cancer risk have been reported in many articles recently, but results were controversial. Therefore the present meta-analysis was conducted to to provide a more precise estimation. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Finally, six case- control studies involving a total of 1,302 cases and 2,391controls for the A1298C polymorphism were included. The meta-analysis showed that significantly increased risk for Asians (CC versus AA, OR=3.799, 95%CI=1.541-9.365, P=0.004; CCversusCA+AA, OR=3.997, 95%CI=1.614-9.900, P=0.003) and Caucasians (CC versus AA, OR=1.797, 95%CI=1.335-2.418, P=0.000; CC+CA versus AA,OR=1.240, 95%CI=1.031-1.492, P=0.022; CCversusCA+AA, OR=1.693, 95%CI=1.280-2.240, P=0.000). In addition, there was an association with risk for both ESCC (CC versus AA, OR=2.529, 95%CI=1.688-3.788, P=0.000; CCversusCA+AA, OR=2.572, 95%CI=1.761-3.758, P=0.000) and esophageal adenocarcinoma (EAC) (CC versus AA, OR=1.592, 95%CI=1.139-2.227, P=0.007; CC+CA versus AA,OR=1.247, 95%CI=1.016-1.530, P=0.035; CCversusCA+AA, OR=1.466, 95%CI=1.069-2.011, P=0.018). This meta-analysis suggested associations of the A1298C polymorphism with increased risk of esophageal cancer in both Asians and Caucasians. In addition, we found that the MTHFR A1298C polymorphism might influence risk ofESCC and EAC in the overall studies.
Highlights
In all human cancers, esophageal cancer (EC), with the five- year survival rate less than 20%, is regarded as one of the most common lethal malignancies worldwide
Characteristics of relevant studies According to our search strategy and inclusion criteria,six studies with full-text articles were remained the relationship of Methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism with EC (Song et al, 2001; Stolzenberg et al, 2003; Gao et al, 2004; Zhang et al, 2008; Ibiebele et al, 2011; Ekiz et al, 2012)
In the A1298C polymorphism, we found that a stronger risk for EC (CCversus AA, Odds ratios (ORs)=1.951, 95%confidence intervals (CIs)=1.4752.581, P=0.000; Dominant model CC+CA versus AA, OR=1.790, 95%CI=1,312-2.444, P=0.000; Recessive model CCversusCA+AA, OR=1.843, 95%CI=1.4142.402, P=0.000) (Figure 1)
Summary
Esophageal cancer (EC), with the five- year survival rate less than 20%, is regarded as one of the most common lethal malignancies worldwide. Squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) are the main histological types, In the “esophageal cancer belt” of the ESCC even has reached 90% (Wheeler et al, 2012). It is a multi-factor and multistep process to develop EC, such as poor nutritional status, drinking of alcohol, smoking, ethnic group, hot beverage and high-temperature cooking methods, serious shortage of vegetable and fruit intake (Yu et al, 1988; Farrow et al, 2000; Lin et al, 2011). Associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and esophageal cancer risk have been reported in many articles recently, but results were controversial. Conclusion: This meta-analysis suggested associations of the A1298C polymorphism with increased risk of esophageal cancer in both Asians and Caucasians. We found that the MTHFR A1298C polymorphism might influence risk ofESCC and EAC in the overall studies
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