食管癌高发区人群Bcl-2基因多态性与贲门癌及癌前病变易感性研究

Research on genetic susceptibility of Bcl-2 gene polymorphism to gastric cardiac carcinoma and precancerous lesions in population with high incidence of esophageal cancer

目的 Bcl-2作为一种癌基因,与肿瘤早期形成密切相关。本研究旨在探讨凋亡抑制基因Bcl-2启动子区-938(C/A)位点单核苷酸多态性(single nucleotide polymorphism,SNP)与河北省南部高发区人群贲门腺癌及其癌前病变遗传易感性的相关性。方法采用病例对照研究方法,选取2007-12-01-2009-12-30河北省南部食管癌高发区人群195名正常对照者、92例贲门癌前病变患者和169例贲门癌患者组织标本进行研究,应用UNIQ-10柱式动物基因组DNA抽提试剂盒进行组织DNA提取,并通过聚合酶链式反应-限制性片段长度多态性分析(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)方法检测Bcl-2-938位点基因型,随机选取不同基因型的标本进行DNA测序,分析该位点多态性与贲门癌及癌前病变的遗传易感性关系。结果 Bcl-2启动子区-938位点CC基因型频率分别为48.5%、47.8%和33.8%,差异有统计学意义,均P<0.05。携带CC基因型的个体与AA基因型相比,贲门癌(P=0.009)与癌前病变(P=0.020)的发病风险增加,经性别、年龄、吸烟和家族史校正后的OR值分别为2.564(95%CI=1.268~5.184)和2.810(95%CI=1.179~6.639)。贲门癌患者组吸烟者比例为56.8%,高于癌前病变组的43.5%和对照组的34.4%,差异有统计学意义,χ^2=18.446,P<0.001;而吸烟阳性组中与AA基因型相比,携带CC基因型(P=0.020)可增加贲门癌的发病风险,经性别、年龄、家族史和饮酒校正后的OR值为3.635(95%CI=1.226~10.777)。结论 Bcl-2-938位点CC基因型可显著增加河北省食管癌高发区人群贲门癌及癌前病变的遗传易感性和发病风险。

OBJECTIVE As a oncogene,Bcl-2 is closely related to the early formation of tumor.This study aimed to investigate the association of single nucleotide polymorphisms(SNP)in transcription start site-938(C/A)on apoptosis-inhibiting gene Bcl-2 with genetic susceptibility of patients with gastric cardiac adenocarcinoma and precancerous lesions in the high-risk areas,south of Hebei Province,China.METHODS From December 1,2007 to December 30,2009,tissue samples were collected from 195 cases healthy controls,92 cases of cardia precancerous lesions and 169 cases of gastric cardiac adenocarcinoma in Southern of Hebei Province.The DNA samples were extracted from different tissues,and the UNIQ-10 Column animal genome isolation kit was used to extract tissue DNA and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)analysis was adopted to detect the genotype of Bcl-2.Samples with different genotypes were randomly selected for DNA sequencing to analyze the relationship between polymorphism of this site and genetic susceptibility to cardiac cancer and precancerous lesions.RESULTS The frequencies of CC genotype at site-938 in Bcl-2 promoter were 48.5%,47.8% and 33.8%,respectively,and the difference was statistically significant(P<0.05)Compared with AA genotype,the risk of cardiac cancer(P=0.009)and precancerous lesions(P=0.020)was increased in individuals with CC genotype.Adjusted by sex,age,smoking and family history,ORvalues were 2.564(95%CI=1.268-5.184)and 2.810(95%CI=1.179-6.639),respectively.The proportion of smokers in patients with cardiac cancer was56.8%,higher than 43.5%in patients with precancerous lesions and 34.4%in the control group,and the difference was statistically significant,χ^2=18.446,P<0.001.Compared with AA genotype,CC genotype(P=0.020)in smoking positive group increased the risk of cardiac cancer.The ORvalue adjusted by sex,age,family history and drinking was 3.635(95%CI=1.226-10.777).CONCLUSION CC genotype in Bcl-2-938(C/A)SNP can significantly increase the risk of gastric cardiac adenocarcinoma and precancerous lesions at high-risk areas of esophageal cancer in China.