TERT-CLPTM1 locus polymorphism (rs401681) is associated with the prognosis of hepatocellular carcinoma

Abstract

Telomere length is associated with the development of hepatocellular carcinoma (HCC), and recent studies have focused on the genetic alteration or polymorphism in telomere-maintaining genes. We examined the clinicopathologic and prognostic value of rs401681 polymorphism, located in the TERT-CLPTM1L locus, in HCC. The relationship between rs401681 variants and telomere length was also analyzed in 156 HCC patients. The rs401681 polymorphism had the following genotype frequencies: C/C in 51.3% of the samples, C/T in 39.7%, and T/T in 9.0%. Telomeres in the tumor samples were 4.04-fold longer, on average, than the telomeres in matched normal samples (SD =1.32), and there were no differences in telomere length according to rs401681 polymorphism (p=0.802). Our results indicate that the rs401681 C allele was significantly associated with increased T and International Union for Cancer Control stages (p<0.01). Univariate and multivariate survival analyses showed that HCC with C allele had poorer prognosis (p<0.01). In conclusion, our findings suggest that rs401681 is a possible prognostic biomarker for HCC patients.

Keywords:

• CLPTM1L polymorphism
• hepatocellular carcinoma
• TERT-CLPTM1L locus
• telomere length

Acknowledgments

This study was supported by grants of the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2014R1A6A3A04058057), and by the Korean Government (MSIP; No 2014R1A5A2010008).

Author contributions

Conceptualization: Lee HW, Lee JH; data curation: Park WJ, Heo YR, Lee HW; formal analysis: Lee HW, Lee JH; funding acquisition: Lee JH; investigation: Park WJ, Park TI, Park SY, Heo YR; methodology: Park WJ, Park TI, Park SY, Heo YR; project administration: Lee HW, Lee JH; resources: Lee HW, Park WJ, Park TI, Park SY, Heo YR; supervision: Lee JH; validation: Lee HW, Lee JH; visualization: Park WJ, Heo YR, Lee JH; writing original draft: Lee HW, Lee JH; writing review and editing: Lee HW, Park WJ, Park TI, Park SY, Heo YR, Lee JH. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.