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中国人群中PLCE1基因的新型功能变异位点与消化道癌易感性的Meta分析

Novel functional variants locus in PLCE1 and susceptibility to digestive tract cancer in the Chinese population: a meta-analysis.

作者信息

Duan Fujiao, Song Chunhua, Dai Liping, Cui Shuli, Zhang Xiaoqin, Zhao Xia

机构信息

1 Department of Hospital Infection Management, Affiliated Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou, Henan - P.R. China.

出版信息

Int J Biol Markers. 2014 Dec 9;29(4):e301-9. doi: 10.5301/jbm.5000090.

DOI:10.5301/jbm.5000090
PMID:24874112
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.

摘要

三项大规模全基因组关联研究(GWAS)已在中国人群中确定了食管鳞状细胞癌(ESCC)和/或贲门腺癌(GCA)的一个共同易感性变异——磷脂酶Cε1(PLCE1)rs2274223。然而,PLCE1 rs2274223 A>G与消化道癌(DTC)风险之间的关联并不一致。因此,我们对已发表的病例对照研究进行了荟萃分析,以更精确地估计PLCE1 rs2274223 A>G与DTC风险之间的关联。进行了全面检索,以确定所有符合条件的关于PLCE1 rs2274223多态性与DTC风险的研究。计算了具有95%置信区间(95%CI)的粗比值比(OR),以估计固定效应或随机效应模型中的关联强度。还评估了异质性和发表偏倚。共确定了15项病例对照研究,包括29805例病例和32225例对照。总体而言,我们发现PLCE1 rs2274223多态性与DTC风险之间存在统计学显著关联(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),但隐性模型未达到统计学显著性(GG vs GA/AA:OR=0.94,95%CI:0.63 - 1.42)。在按癌症类型进行的亚组分析中,我们在ESCC和GCA亚组中观察到DTC有显著风险。当按对照来源分层时,基于人群的亚组分析结果表明,除了基于医院的亚组外,变异G等位基因通常可能会显著增加DTC风险。总之,PLCE1 rs2274223多态性可能用作DTC易感性的潜在生物标志物,特别是在中国人群的ESCC和GCA中。

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