Leukocyte telomere length-related rs621559 and rs398652 genetic variants influence risk of HBV-related hepatocellular carcinoma

PLoS One. 2014 Nov 3;9(11):e110863. doi: 10.1371/journal.pone.0110863. eCollection 2014.


Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10(-6)). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10(-6)). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles*
  • Carcinoma, Hepatocellular / etiology*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Variation
  • Genome-Wide Association Study
  • Genotype
  • Hepatitis B / complications*
  • Hepatitis B / genetics*
  • Hepatitis B virus*
  • Humans
  • Leukocytes*
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk
  • Risk Factors
  • Telomere / genetics*

Grants and funding

This study was supported by the National Natural Science Foundation of China (81201586 & 31271382); Beijing Natural Science Foundation (5122020); the open project of State Key Laboratory of Molecular Oncology (SKL-KF-2013-03); Beijing Higher Education Young Elite Teacher Project (YETP0521); Program for Changjiang Scholars and Innovative Research Team in University (IRT13045); Beijing City Talent Training Project (2012D009016000002); Shandong Provincial Natural Science Foundation (Y2008C36). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.