PLCE1 rs2274223 A>G polymorphism and cancer risk: a meta-analysis.

ABSTRACT

Phospholipase C epsilon 1 gene (PLCE1) encodes a phospholipase enzyme which regulates various physiological processes (cell growth, differentiation, and apoptosis) and is supposed to play a critical role in carcinogenesis. Recently, a single nucleotide polymorphism (rs2274223 A>G) in PLCE1 was reported as a novel susceptibility locus for esophageal and gastric cancers by genome-wide association studies performed in Chinese population. However, individual association studies replicating this finding showed inconclusive results. Therefore, we performed a meta-analysis of eligible studies to derive precise estimation of the association of PLCE1 rs2274223 A>G polymorphism with cancer risk. We performed pooled analysis of 12 case­control studies including 7,622 cases and 9,555 controls. Odds ratios and 95 % confidence interval were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity, cancer types, and source of controls. All statistical analyses were performed by MIX 2.0 software. We found that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of cancer in log additive/dominant model and at allele level (GG vs. AA OR = 1.24, 95 % CI = 1.01­1.53, P = 0.039; AG vs. AA OR = 1.24, 95 % CI = 1.16­1.32, P < 0.001; AG + GG vs. AA OR = 1.22, 95 % CI = 1.12­1.34, P < 0.001; and G vs. A allele OR = 1.15, 95 % CI = 1.05­1.25, P = 0.002). Further, stratified analysis showed elevated risk of only gastric and esophageal tumors. Sub-group analysis based on ethnicity suggests PLCE1 polymorphism conferred significant risk among Asian (Chinese) but not in Caucasian. In conclusion, PLCE1 rs2274223 polymorphism may be used as potential biomarker for cancer susceptibility particularly for esophageal/gastric cancer and for the Chinese population.