Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one of major lethal causes in worldwide, especially in patients with hepatitis B virus (HBV) infection (Chemin and Zoulim, 2009)
These findings suggest that PINX1 rs1469557 but not telomerase associated protein 1 (TEP1) rs1469557 might play a role in HCC progression in Thai patients with liver cirrhosis (LC) and be used as the prognosis marker to predict overall survival in HCC patients
We investigated the genetic variation in case of genetic polymorphisms of TEP1 rs1713449 and PINX1 rs1469557 and the effect of these variations on clinical outcomes in HCC patients
Summary
Hepatocellular carcinoma (HCC) is one of major lethal causes in worldwide, especially in patients with hepatitis B virus (HBV) infection (Chemin and Zoulim, 2009). Viral and immunological and host genetic factors involve in pathogenesis of HCC and progression of tumor cells. HCC occurrence is multistep process beginning from chronic hepatitis, cirrhosis to HCC progression. Telomerase participates in cancer development by controlling telomere length and chromosomal stability as well as growth of tumor cells. Mutation of telomerase gene was reported as influence factor on the presence of liver cirrhosis and risk of HCC (Hartmann et al, 2011). Telomerase composes of 2 components, ribonucleoprotein complex (functional RNA component known as hTR or hTERC and catalytic protein or hTERT) and some protein complex called telomerase associated proteins such as telomerase associated protein 1 (TEP1), P23/p90 and hGAR1 that play a role in telomerase function and regulation (Cong et al, 2002). Regulation of telomerase relies on the control of tumor suppressor or telomerase inhibitor gene called PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1) (Chang et al, 2012)
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