Abstract
BackgroundTo 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.MethodsA 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.ResultsOverall, 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.ConclusionOur 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.
Highlights
Digestive tract cancer (DTC) referring to a group of malignancies is the most common cancer worldwide
Accumulative evidence has shown that genetic factors, especially gene polymorphisms, which involve in multiple biological pathways, such as carcinogen metabolism, apoptosis, DNA repair, cell cycle regulation, and other cellular processes, play important roles in the etiology of digestive tract cancer (DTC) [9,10,11,12]
Test of Heterogeneity When evaluating the association between the phospholipase C epsilon 1 (PLCE1) rs2274223 polymorphism and the susceptibility to DTC, we found that there was significant heterogeneity for the homozygote comparison (GG vs. AA: Pheterogeneity = 0.001, I2 = 65.60%), dominant model comparison (GG/GA vs. AA: Pheterogeneity = 0.009, I2 = 57.60%) and recessive model comparison (GG vs. GA/AA: Pheterogeneity = 0.005, I2 = 60.00%) but not for the heterozygote comparison (GA vs. AA: Pheterogeneity = 0.113, I2 = 35.70%)
Summary
Digestive tract cancer (DTC) referring to a group of malignancies (e.g., located in oral cavity, pharynx and larynx, esophagus, stomach, small and large intestines) is the most common cancer worldwide. It has been estimated that there were nearly 316,970 new diagnosed cases and 147,150 deaths caused by DTC in the United States in 2011 [1]. Identification of potential risk factors for DTC may contribute to the prevention and early diagnoses of these lethal cancers. Alcohol consumption and tobacco smoke are the well-recognized risk factors for DTC [6]. Despite the high prevalence of Helicobacter pylori (HP) infection in gastric cancer, human papillomavirus (HPV) is recognized as a major risk factor for oropharygeal cancer [7,8]. 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
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call