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Abstract Details
Prognostic impact of telomere maintenance gene polymorphisms in hepatocellular carcinoma patients with chronic Hepatitis B
Jung SW, Park NH, Shin JW, Park BR, Kim CJ, Lee JE, Shin ES, Kim JA, Chung YH. Hepatology. 2013 Aug 1. doi: 10.1002/hep.26655. [Epub ahead of print]
Source
Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea.
Abstract
Our goal was to determine whether single nucleotide polymorphisms (SNPs) of telomere maintenance genes influence the development and clinical outcomes of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. We evaluated 20 SNPs of five telomere maintenance genes in 702 patients with HCC and 351 HBsAg positive controls without HCC. Significant SNPs were then validated in an independent cohort of 857 HCCs and 429 controls. We assessed the association of each SNP with the development and overall survival by multivariate Cox proportional analysis. A significantly increased risk of HCC development was identified for TEP1 rs1713449 SNP in both the discovery and replication phases (ORcombined , 1.42; P = 9.378 × 10-5 ). In addition, the SNPs of TEP1 rs1713449, TEP1 rs872072, POT1 rs7784168, TERT rs13167280, and TERF1 rs2306494 had a significant effect on the overall survival and a similar survival effect was validated in the replication cohort. Moreover, there was a significant dose-dependent association between the number of putative high-risk genotypes of the above 5 SNPs regarding the overall survival. The median survival time of HCC with ≤ 2 putative high-risk genotypes was significantly prolonged compared to those with ≥ 3 high-risk genotypes (85 vs. 44 months, respectively, log-rank P = 4.483 × 10-5 ), which was demonstrated in the replication cohort (52 vs. 37 months, respectively, log-rank P = 0.026). Conclusion: These observations suggest that the SNPs of telomere maintenance genes play a potential role in the development and survival of HCC patients with chronic HBV infection.