EP300基因外显子区SNP与中国人食管鳞癌易感性关联分析

Correlation of genetic polymorphism in the exon region of EP300 gene with susceptibility to esophageal squamous cell carcinoma in Chinese population

目的食管鳞癌(esophageal squamous cell carcinoma,ESCC)是我国高发的恶性肿瘤,EP300在ESCC的发生发展中起到重要作用,本研究拟探索EP300基因外显子区的单核苷酸多态性(single-nucleotide polymorphism,SNP)与中国人群ESCC易感性的关联。方法从千人基因组计划中寻找EP300基因外显子区的SNP,发现2个位点(rs146242251和rs20551)在中国人群的最小等位基因型频率>1%。收集2000-01-01-2009-12-31中国医学科学院肿瘤医院就诊的ESCC患者528例,收集同期在社区营养调查中的健康人571名作为对照人群,使用Taqman基因分型法对这2个SNP进行了基因分型。SNP与ESCC风险之间的关联使用Logistic回归计算,并校正性别、年龄和吸烟饮酒状态。结果 EP300基因外显子的rs20551的低频变异与ESCC易感性之间无显著关联。与携带rs20551的AA基因型人群相比,携带AG基因型人群食管癌的患病风险差异无统计学意义(OR=1.09,95%CI:0.77~0.54,P=0.620),携带GG基因型人群食管癌的患病风险差异也无统计学意义(OR=1.39,95%CI:0.40~4.80,P=0.604)。而另一个错义SNP(rs146242251)与ESCC易感性显著相关。相比携带rs146242251的AA基因型人群,携带AG基因型的人群具有更高的ESCC发病风险(OR=2.20,95%CI:1.14~4.27,P=0.019)。结论 EP300基因外显子区遗传多态性与中国人群ESCC易感性相关,提示其可能在ESCC的发生发展中发挥重要作用。

OBJECTIVE Esophageal squamous cell carcinoma（ESCC）is a malignant tumor with high incidence in China.EP300 plays an important role in the development of ESCC.In this study,the relationship between the single nucleotide polymorphism（SNP）in the exon region of EP300 gene and the susceptibility to esophageal squamous cell carcinoma in Chinese population was explored.METHODS The SNPs in the exon region of the EP300 gene were searched from the1000-genome project.The minimum allele frequencies of the two sites（rs146242251 and rs20551）in the Chinese population were found to be greater than 〉1%.A total of 528 ESCC patients from January 1,2000 to December 31,2009 at National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College were collected.A total of 571 healthy people in the community nutrition survey as control subjects were collected at the same period.The Taqman genotyping method was used to genotype these two SNPs in 528 patients with esophageal squamous cell carcinoma and 571 healthy controls.Associations between single nucleotide polymorphisms and ESCC risk were calculated by using logistic regression and corrected for gender,age,and smoking and drinking status.RESULTS There was no significant correlation between low frequency variation of rs20551 in the exon of EP300 gene and ESCC susceptibility.Compared with the rs20551 AA genotype carriers,there was no significant difference of the risk of ESCC in the AG genotype carriers（OR=1.09,95% confidence interval：0.77 to 0.54,P=0.620）,and also no significant difference of the risk of ESCC in the GG genotype carriers（OR=1.39,95% confidence interval：0.40 to 4.80,P=0.604）.Another missense SNP（rs146242251）was significantly associated with the risk of ESCC.Compared with AA genotype carriers,AG genotype carriers were associated with an increased risk of esophageal squamous cell carcinoma with an OR of 2.20（95%confidence interval：1.14-4.27,P=0.019）.CONCLUSION The genetic polymorphism in the exon region of EP300 gene correlates with susceptibility to ESCC in Chinese population,suggesting that EP300 may play an important role in the development of ESCC.