title: Leukocyte telomere length-related rs621559 and rs398652 genetic variants influence risk of HBV-related hepatocellular carcinoma.
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.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Pan
authors.affiliation: Clinical Laboratory, Jinan Infectious Disease Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Guangxia
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Huaixin
authors.initials: H
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Li
authors.affiliation: Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics*; D006515:Hepatitis B virus; D006801:Humans; D007962:Leukocytes; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012307:Risk Factors; D016615:Telomere / Q000235:genetics*