Sriprapun Methee, Chuaypen Natthaya, Khlaiphuengsin Apichaya, Pinjaroen Nutcha, Payungporn Sunchai, Tangkijvanich Pisit
Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand E-mail :
Asian Pac J Cancer Prev. 2016;17(4):2019-25. doi: 10.7314/apjcp.2016.17.4.2019.
Hepatocellular carcinoma (HCC) is major health problem with high mortality rates, especially in patients with hepatitis B virus (HBV) infection. Telomerase function is one of common mechanisms affecting genome stability and cancer development. Recent studies demonstrated that genetic polymorphisms of telomerase associated genes such as telomerase associated protein 1 (TEP1) rs1713449 and PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1) rs1469557 may be associated with risk of HCC and other cancers. In this study, 325 patients with HCC and 539 non-HCC groups [193 healthy controls, 80 patients with HBV-related liver cirrhosis (LC) and 266 patients with HBV-related chronic hepatitis (CH)] were enrolled to explore genetic polymorphisms of both SNPs using the allelic discrimination method based on MGB probe TaqMan real time PCR. We demonstrated that all genotypes of both genes were in Hardy-Wienberg equilibrium (>0.05). Moreover, there was no significant association between rs1713449 genotypes and HCC risk, HCC progression and overall survival (>0.05). Interestingly, we observed positive association of rs1469557 with risk of HCC when compared with the LC group under dominant (CC versus CT+TT, OR=1.89, 95% CI= 1.06-3.40, P=0.031) and allelic (C versus T alleles, OR=1.75, 95% CI=1.04-2.94, P=0.033) models, respectively. Moreover, overall survival of HCC patients with CC genotype of rs1469557 was significantly higher than non-CC genotype (Log-rank P=0.015). These findings suggest that PINX1 rs1469557 but not TEP1 rs1469557 might play a role in HCC progression in Thai patients with LC and be used as the prognosis marker to predict overall survival in HCC patients.
肝细胞癌（HCC）是一个主要的健康问题，死亡率很高，尤其是在乙型肝炎病毒（HBV）感染患者中。端粒酶功能是影响基因组稳定性和癌症发展的常见机制之一。最近的研究表明，端粒酶相关基因的遗传多态性，如端粒酶相关蛋白1（TEP1）rs1713449和PIN2/TERF1相互作用端粒酶抑制剂1（PINX1）rs1469557，可能与HCC及其他癌症的风险相关。在本研究中，纳入了325例HCC患者和539例非HCC组[193例健康对照、80例HBV相关肝硬化（LC）患者和266例HBV相关慢性肝炎（CH）患者]，采用基于MGB探针TaqMan实时PCR的等位基因鉴别方法，探索这两个单核苷酸多态性（SNP）的基因多态性。我们证明这两个基因的所有基因型均处于Hardy-Weinberg平衡（>0.05）。此外，rs1713449基因型与HCC风险、HCC进展和总生存期之间无显著关联（>0.05）。有趣的是，与LC组相比，在显性模型（CC与CT+TT，OR=1.89，95%CI=1.06-3.40，P=0.031）和等位基因模型（C与T等位基因，OR=1.75，95%CI=1.04-2.94，P=0.033）下，我们观察到rs1469557与HCC风险呈正相关。此外，rs1469557 CC基因型的HCC患者的总生存期显著高于非CC基因型（对数秩检验P=0.015）。这些发现表明，PINX1 rs1469557而非TEP1 rs1469557可能在泰国LC患者的HCC进展中起作用，并可作为预测HCC患者总生存期的预后标志物。
