let-7启动子区基因多态性与肝细胞肝癌遗传易感性的关联

Relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma

目的 探讨let-7启动子区域基因多态与中国人群肝细胞肝癌（HCC）易感性的关联.方法 采用病例-对照研究设计,以经确诊的1300例乙型肝炎病毒（HBV）阳性HCC患者作为病例组,选取1344例HBV持续性感染患者作为对照组.收集研究对象血液标本5ml,提取基因组DNA.以let-7启动子区rs10877887和rs13293512为研究位点,应用TaqMan探针方法进行多态性检测,并用logistic回归计算OR（95％CI）值,比较不同基因型与HCC患病风险的关系.结果 rs10877887位点3种基因型TT、CT及CC在病例组分布频率分别为43.0％ （542/1261）、44.7％ （564/1261）及12.3％（ 155/1261）；在对照组中分别为44.0％（ 581/1319）、44.4％（ 585/1319）及11.6％ （153/1319）.rsl3293512位点3种基因型TT、CT及CC在病例组分布频率分别为32.0％（ 406/1270）、48.1％（611/1270）及19.9％ （253/1270）,在对照组中分别为33.1％ （427/1291）、49.4％（ 638/1291）及17.5％ （226/1291）.多因素logistic回归分析显示,携带rs10877887位点至少1个突变等位基因C的个体与携带TT基因型的个体相比,HCC患病风险差异无统计学意义（CC＋ CT对TT：调整OR=1.05,95％ CI：0.90～ 1.23）；与携带TT基因型个体比较,携带rs13293512位点至少1个突变等位基因C的个体HCC患病风险差异无统计学意义（CC＋ CT对TT：调整OR=1.06,95％ CI：0.89～ 1.25）.两位点联合分析显示：携带0、1、2及3～4个突变等位基因C的患者在病例组分别占13.3％（ 164/1235）、36.2％ （447/1235）、33.0％ （408/1235）及17.5％ （216/1235）,在对照组中分别占14.2％ （181/1269）、37.0％ （469/1269）、33.1％ （420/1269）及15.7％ （199/1269）.携带1、2及3～4个突变等位基因C个体的HCC患病风险分别是不携带突变等位基因个体的1.05（0.81～1.34）、1.07（0.83～1.38）、1.22（0.91 ～ 1.62）倍,呈一致趋势,但无统计学意义（Wald x2=1.79,P=0.181）.结论 let-7启动子区域rs10877887和rs13293512位点多态改变可能不是中国人群HCC易感性标志.

Objective The purpose of this study was to discuss the relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma （ HCC ） in Chinese population.Methods In this case-control study,1300 cases of HBV positive patients were recruited in case group and another 1344 cases of persistent chronic HBV carriers were selected as control.5 ml of blood sample was collected from each subject,from which the DNA was extracted; and rs10877887 and rs13293512 in promoter region let-7 were selected as the study sites.The polymorphism was detected by TaqMan allelic discrimination assay and the OR value（95% CI）was evaluated by Logistic Regression Method to analyze the relationship between susceptibility to HCC and different genotypes.Results The frequencies of genotype TT,CT and CC in site rs10877887 were 43.0% （542/1261）,44.7% （564/1261）and 12.3%（ 155/1261 ） respectively in case group; while separately 44.0% （ 581/1319 ）,44.4% （ 585/1319 ） and 11.6% （153/1319） in control group.The frequencies of genotype TT,CT and CC in site rs13293512 were 32.0% （ 406/1270 ）,48.1% （ 611/1270 ） and 19.9% （ 253/1270 ） respectively in case group; while separately 33.1% （427/1291）,49.4% （638/1291）and 17.5% （226/1291）in control group.The results of multifactor logistic regression analysis showed no statistical significance in the relationship between different genotype TT,mutated genotype C in site rs10877887 and susceptibility to HCC （ CC ＋ CT vs TT,adjusted OR =1.05,95 % CI：0.90 - 1.23） ; and either no statistical significance in the relationship between different genotype TT,mutated genotype C in site rs13293512 and susceptibility to HCC （CC ＋ CT vs TT,adjusted OR =1.06,95% CI：0.89 - 1.25）.The united-analysis of the two sites showed the frequencies of 0,1,2 and 3 -4 mutated-genotype C were 13.3% （ 164/1235 ）,36.2% （447/1235）,33.0% （408/1235） and 17.5%（216/1235） respectively in case group; and separately 14.2% （181/1269）,37.0% （469/1269）,33.1% （420/1269） and 15.7% （199/1269）in control group.The susceptibility to HCC in 1,2,3 -4 mutated-genotype C carriers were 1.05（0.81 - 1.34）,1.07（0.83 - 1.38） and 1.22（0.91 - 1.62） times of the non-mutated genotype subjects; but there was no statistical significance （Wald x2 =1.79,P =0.181 ）.Conclusion The polymorphism of study sites rs10877887 and rs13293512 may not be the biomarker of susceptibility to HCC in Chinese.