Increased risk of developing digestive tract cancer in subjects carrying the PLCE1 rs2274223 A>G polymorphism: evidence from a meta-analysis

Abstract

Background: To date, the association between phospholipase C epsilon 1 (PLCE1) rs2274223 A>G and risk of digestive tract cancer (DTC) remains inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis on all eligible case-control studies involving 8281 cases and 10,532 controls.

Methods: A comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and digestive tract cancer risk. The pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using a fixed or random effect model. Heterogeneity, publication bias, and sensitivity analysis were also explored.

Results: Overall, the PLCE1 rs2274223 A>G polymorphism was associated with risk of DTC in all genetic models (GA vs. AA: OR = 1.21, 95% CI = 1.14-1.29, P<0.001; GG vs. AA: OR = 1.30, 95% CI = 1.06-1.60, P = 0.012; GG/GA vs. AA: OR = 1.20, 95% CI = 1.10-1.32, P<0.001; GG vs. GA/AA: OR = 1.21, 95% CI = 1.01-1.46, P = 0.040). The recessive model did not reach statistically significance when the P values were Bonferroni corrected to 0.0125. In the stratified analysis by cancer type, ethnicity, and source of controls, significantly increased risk was observed for esophagus cancer, Asians in three genetic models (heterozygote comparison, homozygote comparison and dominant model), population-based studies in all genetic models, and for gastric cancer in the heterozygote comparison and dominant model after Bonferroni correction. However, in the subsite of gastric cancer, no significant association was found either in cardia or non-cardia gastric cancer.

Conclusion: Our study indicated that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of DTC, especially among Asian populations. Due to some minor limitations, our findings should be confirmed in further studies.

Figure 1. Flow diagram summarizing the search strategy.

Figure 2. Forest plot from the meta-analysis of PLCE1 rs2274223 A>G polymorphism and the risk of DTC stratified by cancer types using dominant genetic model.

Figure 3. Forest plot from the meta-analysis of PLCE1 rs2274223 A>G polymorphism and the risk of DTC stratified by ethnicity using dominant genetic model.

Figure 4. Begg’s funnel plot of publication bias test.

(A) GA vs. AA; (B) GG/GA vs. AA. Each point represents a separate study for the indicated association. Log (OR), natural logarithm of OR. Horizontal line, mean effect size.