ERCC1基因多态性与肝癌的相关性研究

The Association Between Polymorphism of ERCC1 Gene and Hepatocellular Carcinoma

目的探讨核酸切除修复基因1(ERCC1)的单核苷酸多态性(SNP)与肝癌易感性的相关性,并研究ERCC1基因多态性和肝癌组织ERCC1蛋白表达的关系。方法本研究纳入肝细胞癌患者及对照组各65例,采用SNa Pshot技术对ERCC1基因rs735482,rs1046282,rs3212948三个多态性位点进行基因分析,免疫组织化学方法检测肝癌组织ERCC1蛋白表达,卡方检验分析上述三个多态性位点基因型在研究对象中的分布情况与及其与肝癌组织ERCC1蛋白表达的关系进行分析,非条件Logistic回归分析法对以上三个SNP位点等位基因和基因型频率与肝癌的发病风险关系进行分析,以P <0. 05表明存在统计学差异。结果对照组中三个多态性位点基因型分布均符合哈温平衡规律。病例组ERCC1基因rs1046282位点基因型频数分别为:CC为8(12. 31%),CT为30(46. 15%),TT为27(41. 54%);对照组该位点基因型频率分布:CC为22(33. 85%),CT为25(38. 46%),TT为18(27. 69%),CC、CT、TT基因型在两组中的频数分布差异具有统计学意义P=0. 012;T等位基因在病例组中的分布频率高于对照组(P=0. 004);与CC基因型比较,携带至少1个突变等位基因T(CT+TT)的个体发生肝癌的风险增加了2. 218倍(P=0. 017)。rs3212948和rs735482位点单核苷酸多态性与肝癌患病风险性不存在相关性(P> 0. 05),以上三个位点的单核苷酸多态性与肝癌组织ERCC1蛋白的表达无相关性(P>0. 05)。结论 ERCC1基因rs1046282位点多态性与肝癌易感性相关,且携带突变T等位基因比携带C等位基因患肝癌的风险率高。尚未发现ERCC1基因rs735482,rs3212948位点突变与肝癌的发病风险存在相关性,这三个位点单核苷酸多态性与肝癌组织ERCC1蛋白表达不相关。

Objective To investigate the association between single nucleotide polymorphism （SNP）of nucleic acid excision repair gene 1 （ERCC1）and susceptibility to hepatocellular carcinoma （HCC）,and further study the association between ERCC1 gene polymorphism and ERCC1 protein expression in canceroustissues. Methods This study included 65 patients with HCC and 65 controls.SNaPshot technique was used for genotyping SNP sites of ERCC1 gene （rs735482,rs1046282,rs3212948）.Immunohistochemistry was used to detect ERCC1 protein expression in cancerous tissues.The distribution of three SNPs genotypes and their relationships with the expression of ERCC1 protein in cancerous tissues wereanalyzed bythesquare test.The unconditional logisticregression was used to analyze differences of allele and genotype distributions of the SNPs and their correlations with the risk of hepatocellular carcinoma,with the statistical difference observed at P 〈0.05. Results The genotype distribution of the three SNPs in the control group met with the Hardy- Weinberg equilibrium.The frequency of genotypes of rs1046282 locus in the case group was 8 （12.31%）for CC,30 （46.15%）for CT,and 27 （41.54%）for TT.The genotype frequency distribution of this locus in the control group：CC was 22 （33.85%）,CT was 25 （38.46%）,TT was 18 （27.69%）,and the frequency distribution of CC,CT,TT genotype between the case group and control group had statistically significant differences （ P =0.012）.T allele at siters1046282in the case group was significantly higher than that in the control group （ P =0.004）.Compared with CC genotype,the risk of hepatocellular carcinoma in the subjects carrying the mutated allele T （CT＋TT）was increased 2.218times （ P =0.017）.There was no correlation between the polymorphisms of rs3212948 and rs735482 and the risk of hepatocellular carcinoma （ P 〉0.05）.TheseSNPs were not associated with the expression of ERCC1 protein in hepatocellular carcinoma. Conclusion The polymorphism of rs1046282 in ERCC1 gene was associated with susceptibility to hepatocellular carcinoma,with the risk of carrying T allele higher than carrying C allele.The rs735482 and rs3212948 mutations of ERCC1 genehave not been found to be associated with the risk of hepatocellular carcinoma.These three SNPs are not associated with ERCC1 protein expression in hepatocellular carcinoma.