Abstract
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.
Highlights
Human telomeres, consisting of ‘‘TTAGGG’’ short repetitive sequences, locate at the ends of chromosomes [1,2]
No statistically significant differences were found between HBVrelated hepatocellular carcinoma (HCC) patients, chronic hepatitis B virus (HBV) carriers and healthy controls for Shandong set and Jiangsu set in terms of median age and sex distribution (P.0.05)
In Shandong set consisting of 1186 patients with HBV-related HCC, 508 chronic HBV carriers as well as 1308 healthy controls, we found that two common single nucleotide polymorphisms (SNPs) (14q21 rs398652 and 1p34.2 rs621559) were significantly associated with HBV-related HCC risk
Summary
Human telomeres, consisting of ‘‘TTAGGG’’ short repetitive sequences, locate at the ends of chromosomes [1,2]. Because of the ‘‘end replication problem’’, telomeres would shorten after each DNA replication and each cell division in normal cells. When telomeres shrink to be tremendously short, these normal cells would go through cellcycle arrest, apoptosis or senescence [1]. In normal human leukocytes without or with little telomerase activity, telomere length shortens with age at a rate of 20,40 base pairs (bp) per year [5,6]. Leukocyte telomere length (LTL) has been associated with risk to developing many malignancies [7,8,9,10,11,12,13,14,15,16,17,18], highlighting the predictive role of LTL in carcinogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
