PLCε1基因rs2274223A〉G多态性与上消化道肿瘤遗传易感性的关系的meta分析

rs2274223 A〉G polymorphism of the PLCεl gene is associated with increased risk of upper gastrointestinal cancer

目的综合评价磷脂酶Cel（PLCε1）基因rs2274223A〉G多态性与上消化道肿瘤遗传易感性的关系。方法通过计算机检索PubMed数据库，并结合文献追溯、手工检索等方法收集所有符合纳入标准的病例对照研究。应用meta分析的方法合并rs2274223多态性与上消化道肿瘤易感性关系的优势比（OR）值，并进行亚组、敏感性、回归分析和文献发表偏倚检验。结果共纳入18篇文献（23项研究数据），其中食管癌16项，胃癌7项；累计患者组16938例，对照组16680例。PLCel基因rs2274223A〉G多态性与上消化道肿瘤发病风险有关；等位基因G较A可增加发病风险。共显性杂合子比较模型、共显性纯合子比较模型、显性遗传模型、隐性遗传模型、等位基因模型均可发挥作用，以共显性纯舍子基因模型为著，GG与AA比较差异有统计学意义[0R=1．37，95％可信区间（95％CI）：1．16～1．62，P=0．001]。PLCε1基因rs2274223A〉G多态性在以上5种基因模型中均显著增加食管鳞状细胞癌（ESCC）的发病风险。与之相反，PLCε1基因rs2274223A〉G多态与胃癌、食管腺癌的发病风险无关。rs2274223多态仅与中国人上消化道肿瘤的发病风险显著相关，与高加索人和其他亚洲人（包括北印度人和朝鲜族人）发病风险无关。结论PLCε1基因rs2274223A〉G多态性与上消化道肿瘤易感性显著相关，尤其是在中国人群及ESCC中。

Objective To assess the association between rs2274223 A〉G polymorphism of the PLCεl（phospholipase C epsilon 1）gene and the susceptibility of upper gastrointestinal cancer using a comprehensive recta-analysis. Methods We searched MED- LINE for all case-control studies on the association between PLCε1 rs2274223 and upper gastrointestinal cancer susceptibility pub- lished before April 2016 using the PubMed search engine. Additional studies were identified by a hand search of references of origi- nal studies or review articles on this topic. Odds ratios and 95 % confidence intervals were calculated by using dominant, recessive and co-dominant genetic models in the random-effects model. Publication bias test, subgroup analysis, regression analysis and sensi- tivity analysis were also performed. Results A comprehensive meta-analysis was conducted on 23 case-control studies,including 13 studies are about esophageal squamous cell carcinoma（ESCC）, 2 are about esophageal adenocarcinoma（EAC）, 1 is esophageal cancer （EC）, 7 are gastric cancer, a total of 16 938 cases, 16 680 controls. Results：Showed the PLCE1 rs2274223A〉G polymorphism have a statistically significant association with an increasing risk of upper gastrointestinal cancer. Compared to allele A,allele G increase the risk of upper gastrointestinal cancer. This included the homozygous genetic model, heterozygous genetic model, the dominant model recessive model, allelic genetic model, especially in the homozygous genetic model（GG vs. AA：OR = 1.37,95% CI：1.16-1. 62 ,P=0. 001）. In a subgroup analysis, the PLCE1 rs2274223 polymorphism was found to be a sensitive marker for ESCC as shown by all genetic models. In contrast,none of the genetic models for gastric cancer or EAC were significant. In subgroup analysis strati- fied by ethnicity,significant association between PLCε1 rs2274223 G allele and the risk of upper gastrointestinal was observed in Chinese population but not in Caucasians or other Asian people（including North Indians and Koreans）. Conclusion In this recta-a- nalysis,the PLCε1 rs2274223A〉G polymorphism was confirmed to have a statistically significant association with an increasing risk of upper gastrointestinal cancer, especially among China populations. The increasing risk was especially observed for ESCC. Due to some minor limitations, our findings should be confirmed in further studies.