53BP1和p53基因多态性与食管鳞癌、贲门腺癌遗传易感性的关系  

Correlation of 53BP1 and p53 Polymorphisms to Susceptibility to Esophageal Squamous Cell Carcinoma and Gastric Cardiac Adenocarcinoma

作　　者：曹延延[1] 葛晖[1] 陈龙奇[2] 陈志峰[3] 温登瑰[3] 李琰[1] 张健慧[1] 

机构地区：[1]河北省肿瘤研究所分子生物学研究室,河北石家庄050011 [2]河北医科大学第四医院胸外科,河北石家庄050011 [3]河北省肿瘤研究所流行病学研究室,河北石家庄050011

出　　处：《癌症》2007年第10期1052-1057,共6页Chinese Journal of Cancer

基　　金：国家自然科学基金(No30371591);河北省自然科学基金(NoC200400062)~~

摘　　要：背景与目的:p53结合蛋白1(53BP1)可通过增强p53的转录活性,而在肿瘤抑制方面发挥重要作用。在53BP1的启动子区-885bp处存在着T到G的单核苷酸多态性(single nucleotide polymorphism,SNP)。本实验探讨53BP1 T885G基因多态性以及p53 Arg72Pro的多态性与中国河北高发区人群食管鳞癌(esophageal squamous cell carcinoma,ESCC)和贲门腺癌(gastric cardiac adenocarcinoma,GCA)遗传易感性的关系。方法:应用引物引入限制性内切酶分析-聚合酶链反应(primer-introduced restriction analysis-polymerase chain reaction,PIRA-PCR)方法,分析624例患者(其中ESCC349例,GCA275例)和635例健康对照者的53BP1 T885G和p53 Arg72Pro的基因型。结果:53BP1 T885G基因型分布在总体ESCC、GCA病例组与健康对照组间差异无统计学意义(P>0.05)。根据吸烟状况和上消化道肿瘤(upper gastrointestinal cancer,UGIC)家族史分层分析显示,T885G基因型分布在病例组与健康对照组差异亦无统计学意义(P>0.05)。与Arg/Arg基因型相比,携带p53Arg72Pro Pro/Pro基因型可降低总体GCA的发病风险,经性别、年龄、吸烟状况和UGIC家族史多因素校正后的OR值为0.79(95%CI=0.64～0.98);分层分析显示Pro/Pro基因型主要降低非吸烟组GCA的发病风险,校正后的OR值为0.72(95%CI=0.54～0.97)。未发现p53Arg72Pro对ESCC发病风险的影响。53BP1T885G和p53Arg72Pro联合分析显示,在携带Pro等位基因(Arg/Pro+Pro/Pro基因型)者中,同时携带T885G的G/G基因型可降低GCA的发病风险,校正后的OR值为0.74(95%CI=0.57～0.95)。结论:53BP1T885G位点可能与中国河北高发区ESCC、GCA的遗传易感性无关,p53Arg72Pro的Pro/Pro基因型可降低高发区GCA的发病风险,同时携带Pro等位基因(Arg/Pro+Pro/Pro基因型)和53BP1 T885G的G/G基因型可降低高发区GCA的发病风险。　BACKGROUND ＆ OBJECTIVE： 53BP1 is one of p53-binding proteins, which can enhance the transcriptional activation of p53 and plays a key role in tumor suppression. A single nucleotide polymorphism （SNP） T885G has been found in the promoter of 53BP1. This study was to investigate the correlation of 53BP1 and p53 SNPs to susceptibility to esophageal squamous cell carcinoma （ESCC） and gastric cardiac adenocarcinoma （GCA） in a high incidence area of Hebei Province in China. METHODS： Genotypes of 53BP1 T885G and p53 Arg72Pro in 349 ESCC patients, 275 GCA patients, and 635 healthy subjects were detected by primer-introduced restriction analysis-polymerase chain reaction （PIRA-PCR）. RESULTS： The overall distribution of 53BP1 T885G was not significantly different between ESCC patients, GCA patients and healthy subjects （P〉0.05）. When stratified by smoking status and family history of upper gastrointestinal cancer （UGIC）, the distribution of 53BP1 T885G was not significantly different between ESCC patients, GCA patients and healthy subjects. Compared with p53 Arg72Pro Arg/Arg genotype, Pro/Pro genotype decreased the susceptibility to GCA [the age, sex, smoking status, and family history adjusted odds ratio （OR）=0.79, 95% confidence interval （CI）=0.64-0.98]. Stratification analysis showed that Pro/Pro genotype decreased the susceptibility to GCA among non-smokers （adjusted OR=0.72, 95% CI=0.54-0.97）, but p53 Arg72Pro had no influence on the susceptibility to ESCC. Stratified by p53 Arg72Pro genotype, 53BP1 T885G G/G genotype reduced the susceptibility to GCA among the individuals with Pro allele （Arg/Pro and Pro/Pro genotypes） （adjusted OR=0.74, 95% CI=0.57-0.95）. CONCLUSION： 53BP1 T885G may not be correlated to the susceptibility to ESCC and GCA in the high incidence area of Hebei Province in China; p53 Arg72Pro Pro/Pro genotype could decrease the susceptibility to GCA; 53BP1 T885G G/G genotype could reduce the susceptibility to GCA among the individuals with p53 Pro

关 键 词：食管肿瘤 贲门肿瘤 鳞状细胞癌 腺细胞癌 P53结合蛋白1 多态性 易感性 

分 类 号：R735[医药卫生—肿瘤]