EGF+61A/G polymorphism contributes to increased gastric cancer risk: evidence from a meta-analysis

Background: Epidermal growth factor (EGF) plays a pivotal role in cell proliferation, differentiation, and tumorigenesis of epithelial tissues. Variation of the EGF +61A/G (rs4444903) can lead to an alteration in EGF production and/or activity, which may result in individual susceptibility to gastric cancer. Studies investigating the association between EGF +61A/G polymorphism and gastric cancer risk produced inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association. Methods: Eligible studies on the association between EGF +61A/G polymorphism and gastric cancer risk were identified by search of electronic databases including PubMed, EMBASE, Cochrane Library, and Chinese Biomedical Literature database (CBM). Data were extracted by two independent authors and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results: Finally, six case-control studies with 1547 gastric cancer cases and 2762 controls were eventually identified. Overall, significant increased gastric cancer risk was found when all studies were pooled in the meta-analysis (GG vs. AA: OR = 1.438, 95% CI 1.021-2.025, P = 0.038; GG + AG vs. AA: OR = 1.256, 95% CI 1.025-1.539, P = 0.028; GG vs. AG + AA: OR = 1.265, 95% CI 1.002-1.596, P = 0.048). In subgroup analysis by ethnicity, source of control, study quality, and HWE in controls, significant increased gastric cancer risk was observed in Asians, population-based studies, high quality studies, and studies consistent with HWE. In subgroup analysis according to tumor location, and histological type, significant association was observed in all subgroups. Conclusions: This meta-analysis suggested that the EGF +61A/G polymorphism contributes to increased gastric cancer risk, especially in Asian populations. Further well-designed studies based on large sample size in diverse populations are needed to confirm this association.