E-钙粘蛋白基因多态性与食管癌、贲门癌的关系

Correlation of E-cadherin Polymorphisms to Esophageal Squamous Cell Carcinoma and Gastric Cardiac Adenocarcinoma

背景与目的:E-钙粘蛋白(E-cadherin,CDH1)是钙粘蛋白家族中的一个成员,与肿瘤侵袭转移密切相关。该基因启动子区存在的多态性位点可通过改变转录活性而影响该蛋白的表达。本研究旨在探讨该基因启动子区C-160A和G-347GA单核苷多态性(single nucleotide polym orphism,SNP)与中国北方人食管鳞状细胞癌(esophagealsquam ous cellcarcinom a,ESCC)、贲门腺癌(gastric cardiacadenocarcinom a,GCA)易感性和淋巴结转移的关系。方法:采用聚合酶链反应-限制性片段长度多态性(polym erase chain reaction-restrictionfragm entlength polym orphism,PCR-RFLP)分析方法检测333名ESCC患者、239名GCA患者和343名健康对照的CDH1C-160A及G-347GA SNP的基因型。结果:CDH1C-160A及G-347GA SNP的基因型及等位基因型分布在总体ESCC患者、GCA患者和健康对照中无显著性差异(P=0.08)。根据吸烟状况及上消化道肿瘤家族史分层分析及淋巴结转移状况的分析也未发现CDH1SNPs对ESCC和GCA发病及淋巴结转移的影响。然而,与G-347GA G/G基因型相比,携带GA等位基因(G/GA+GA/GA基因型)可显著增加GCA患病风险,经性别、年龄校正后的OR值为1.45(95%CI=1.03～2.04)。应用EH软件分析显示。

BACKGROUND & OBJECTIVE: E-cadherin (CDH1) relates with invasion and metastasis of various cancers. Polymorphisms in the promoter region of E-cadherin gene may modify its transcriptional activity and protein level. This study was designed to investigate the correlation of CDH1 C-160A and G-347GA single nucleotide polymorphisms(SNPs) to susceptibilities and lymphatic metastases of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in northern China population. METHODS: CDH1 promoter SNPs (C-160A and G-347GA) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 333 ESCC patients, 239 GCA patients, and 343 healthy controls. The combined effect of C-160A and G-347GA was analyzed by EH software. RESULTS: The overall genotype and allelotype distributions of C-160A and G-347GA in ESCC and GCA patients were not significantly different from those in healthy controls (P = 0.08). When stratified by smoking status, family history of upper gastrointestinal cancer, and lymph node metastasis state, CDH1 SNPs also did not significantly influence the development and lymphatic metastasis of ESCC and GCA. However, compared with individuals with G-347GA G/G genotype, individuals with GA allele (G/GA or GA/GA genotype) had significantly higher risk to develop GCA [age and gender adjusted odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.03-2.04]. The haplotype distribution of CDH1 in the 333 ESCC patients was significantly different from that in the 343 healthy controls (P = 0.008). Compared with -160C/-347G haplotype, -160A/-347GA haplotype significantly increased the risk of developing ESCC (age and gender adjusted OR = 24.26, 95% CI = 3.25-180.87). CONCLUSIONS: CDH1 C-160A SNP has no relation with susceptibility and lymphatic metastasis of ESCC and GCA. However, individuals with G-347GA GA allele have high risk of developing GCA; individuals with -160A/-347GA haplotype have high risk of developing ESCC.