Novel Functional Variants Locus in PLCE1 and Susceptibility to Digestive Tract Cancer in the Chinese Population: A Meta-Analysis

Abstract

Three large-scale genome-wide association studies (GWAS) have identified a shared susceptibility variation phospholipase C epsilon 1 (PLCE1) rs2274223 for esophageal squamous cell carcinoma (ESCC) and/or gastric cardia adenocarcinomas (GCA) in the Chinese population. However, the association between PLCE1 rs2274223 A>G and the risk of digestive tract cancer (DTC) has been inconsistent. We therefore carried out a meta-analysis of published case-control studies to derive a more precise estimation of the association between PLCE1 rs2274223 A>G and DTC risk. A comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and DTC risk. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the strength of associations in fixed or random effect models. Heterogeneity and publication bias were also assessed. A total of 15 case-control studies were identified, including 29,805 cases and 32,225 controls. Overall, we found a statistically significant association between the PLCE1 rs2274223 polymorphism and DTC risk (G vs A: OR=1.29, 95% CI: 1.17-1.43; GA vs AA: OR=1.33, 95% CI: 1.18-1.51; GG vs AA: OR=1.71, 95% CI: 1.26-2.32; GG/GA vs AA: OR=1.33, 95% CI: 1.17-1.51), but the recessive model did not reach statistical significance (GG vs GA/AA: OR=0.94, 95% CI: 0.63-1.42). In the subgroup analysis by cancer types, we observed a significant risk for DTC in the ESCC and GCA subgroups. When stratified for source of controls, the results of the population-based subgroup analysis showed that the variant G allele might generally induce a significantly increased risk of DTC, except in hospital-based subgroups. In conclusion, PLCE1 rs2274223 polymorphism may be used as a potential biomarker for DTC susceptibility particularly for ESCC and GCA in the Chinese population.