Huang Fang, Hu Ling-min, Liu Ji-bin, Zhang Yi-xin, Hu Zhi-bin
School of Basic Medicine, Nantong University, Nantong 226001, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2011 Dec;45(12):1093-8.
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.
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.
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 χ(2) = 1.79, P = 0.181).
The polymorphism of study sites rs10877887 and rs13293512 may not be the biomarker of susceptibility to HCC in Chinese.
本研究旨在探讨中国人群中let-7启动子区域基因多态性与肝细胞癌(HCC)遗传易感性之间的关系。
在这项病例对照研究中,病例组招募了1300例HBV阳性患者,另选1344例持续性慢性HBV携带者作为对照组。从每个受试者采集5ml血液样本,从中提取DNA;选择let-7启动子区域的rs10877887和rs13293512作为研究位点。采用TaqMan等位基因鉴别分析检测多态性,并通过Logistic回归方法评估OR值(95%CI),以分析HCC易感性与不同基因型之间的关系。
病例组中rs10877887位点的基因型TT、CT和CC频率分别为43.0%(542/1261)、44.7%(564/1261)和12.3%(155/1261);而对照组分别为44.0%(581/1319)、44.4%(585/1319)和11.6%(153/1319)。病例组中rs13293512位点的基因型TT、CT和CC频率分别为32.0%(406/1270)、48.1%(611/1270)和19.9%(253/1270);而对照组分别为33.1%(427/1291)、49.4%(638/1291)和17.5%(226/1291)。多因素Logistic回归分析结果显示,rs10877887位点不同基因型TT、突变基因型C与HCC易感性之间的关系无统计学意义(CC + CT vs TT,校正OR = 1.05,95%CI:0.90 - 1.23);rs13293512位点不同基因型TT、突变基因型C与HCC易感性之间的关系也无统计学意义(CC + CT vs TT,校正OR = 1.06,95%CI:0.89 - 1.25)。两个位点的联合分析显示,病例组中0、1、2和3 - 4个突变基因型C的频率分别为13.3%(164/1235)、36.2%(447/1235)、33.0%(408/1235)和17.5%(216/1235);对照组分别为14.2%(181/1269)、37.0%(469/1269)、33.1%(420/1269)和15.7%(199/1269)。1、2、3 - 4个突变基因型C携带者的HCC易感性是非突变基因型受试者的1.05(0.81 - 1.34)、1.07(0.83 - 1.38)和1.22(0.91 - 1.62)倍;但无统计学意义(Wald χ(2)=1.79,P = 0.181)。
rs10877887和rs13293512研究位点的多态性可能不是中国人HCC易感性的生物标志物。