TERT启动子区rs6853669和-124 C>T、-146 C>T相关性及其与肝细胞肝癌发病相关性研究

The Correlation Between TERT Promoter Regions rs6853669 and-124 C>T,-146 C>T and Their Associations with Hepatocellular Carcinoma

目的探讨端粒酶逆转录酶(TERT)基因启动子区单核苷酸多态性rs2853669和体细胞突变-124 C>T、-146 C>T相关性及其与肝细胞肝癌(HCC)临床病理特征的相关性。方法根据术后病理结果纳入65例HCC石蜡包埋组织基因组DNA标本,根据常规体检结果纳入65例表观健康人外周血DNA标本作为对照。-124C>T、-146 C>T和rs2853669基因型采用Sanger测序法进行检测。结果在HCC患者和对照组中,rs2857669的TT、TC、CC型分别为28例、25例、12例和33例、24例、8例,两组间基因频率差异无统计学意义(χ^(2)=1.230,P=0.541);HCC患者-124/-146体细胞突变共计31例(47.7%),健康对照组0例(0%)。在HCC患者中,rs2853669 TT、TC、CC型的-124/-146体细胞突变频率显著增加,依次为32.1%(9例)、52.0%(13例)、75.0%(9例),差异有统计学意义(χ^(2)=6.487,P=0.039)。与非共同热点/体细胞突变组(43例)比较,rs2853669和-124/-146共同突变(22例)的HCC患者的年龄和肿瘤分期差异具有统计学意义(χ^(2)=4.219,P=0.040和χ^(2)=6.172,P=0.040)。结论rs2853669多态性不是肝癌易感的危险遗传位点,但携带rs2853669突变的HCC患者更易发生-124/-146体细胞突变;rs2853669、-124 C>T和-146 C>T共同突变与HCC的年龄和恶性度增加有关。

Objective To investigate the relationship between single nucleotide polymorphism rs2853669 in the promoter region of telomerase reverse transcriptase(TERT)gene and somatic mutations-124 C>T,-146 C>T,and their relationships with the pathogenesis of hepatocellular carcinoma(HCC).Methods According to the postoperative pathological results,65 paraffin embedded tissue genomic DNA samples of HCC were included as cases,while 65 peripheral blood DNA samples of apparently healthy people were included as controls according to the results of routine physical examination.-124C>T,-146C>T and rs2853669 genotypes were detected by Sanger sequencing.Results Among HCC patients and the control group,TT,TC and CC types of rs2857669 were 28,25,12 and 33,24 and 8,respectively.There was no significant difference in gene frequency between the two groups(χ^(2)=1.230,P=0.541).There were 31 cases(47.7%)of-124/-146 somatic mutations in HCC patients and 0 cases(0%)in the healthy control group.In HCC patients,rs2853669 TT,TC,CC type-124/-146 somatic mutation frequency increased significantly,followed by 32.1%(9 cases),52.0%(13 cases),75.0%(9 cases),with a significant difference(χ^(2)=6.487,P=0.039).Compared with the non-co-mutation group(43 cases),age and tumor stage of HCC patients with rs2853669 and-124/-146 co-mutation(22 cases)were significantly different(χ^(2)=4.219,P=0.040 andχ^(2)=6.172,P=0.040).Conclusion Rs2853669 polymorphism is not a risk genetic locus for HCC susceptibility,but HCC patients with rs2853669 mutation are more prone to-124/-146 somatic mutation;rs2853669,-124C>T and-146 C>T co-mutations are associated with increased age and malignancy of HCC.