Dataset Information

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.

SUBMITTER: Pan W

PROVIDER: S-EPMC4218833 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Pan Wenting W Cheng Guangxia G Xing Huaixin H Shi Juan J Lu Chao C Wei Jinyu J Li Lichao L Zhou Changchun C Yuan Qipeng Q Zhou Liqing L Yang Ming M

PloS one 20141103 11

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 hea ...[more]

PMID: 25365256

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Project description:In this study, we examined 130 patients with pituitary adenomas (PAs) and 320 healthy subjects, using DNA samples from peripheral blood leukocytes purified through the DNA salting-out method. Real-time polymerase chain reaction (RT-PCR) was used to assess single nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (RLTLs), while enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of TERF1, TERF2, TNKS2, CTC1, and ZNF676 in blood serum. Our findings reveal several significant associations. Genetic associations with pituitary adenoma occurrence: the TERF1 rs1545827 CT + TT genotypes were linked to 2.9-fold decreased odds of PA occurrence. Conversely, the TNKS2 rs10509637 GG genotype showed 6.5-fold increased odds of PA occurrence. Gender-specific genetic associations with PA occurrence: in females, the TERF1 rs1545827 CC + TT genotypes indicated 3.1-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was associated with 4.6-fold increased odds. In males, the presence of the TERF1 rs1545827 T allele was associated with 2.2-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was linked to a substantial 10.6-fold increase in odds. Associations with pituitary adenoma recurrence: the TNKS2 rs10509637 AA genotype was associated with 4.2-fold increased odds of PA recurrence. On the other hand, the TERF1 rs1545827 CT + TT genotypes were linked to 3.5-fold decreased odds of PA without recurrence, while the TNKS2 rs10509637 AA genotype was associated with 6.4-fold increased odds of PA without recurrence. Serum TERF2 and TERF1 levels: patients with PA exhibited elevated serum TERF2 levels compared to the reference group. Conversely, patients with PA had decreased TERF1 serum levels compared to the reference group. Relative leukocyte telomere length (RLTL): a significant difference in RLTL between the PA group and the reference group was observed, with PA patients having longer telomeres. Genetic associations with telomere shortening: the TERF1 rs1545827 T allele was associated with 1.4-fold decreased odds of telomere shortening. In contrast, the CTC1 rs3027234 TT genotype was linked to 4.8-fold increased odds of telomere shortening. These findings suggest a complex interplay between genetic factors, telomere length, and pituitary adenoma occurrence and recurrence, with potential gender-specific effects. Furthermore, variations in TERF1 and TNKS2 genes may play crucial roles in telomere length regulation and disease susceptibility.

Project description:BackgroundRelative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.ObjectiveWe performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.Design, setting, and participantsGenotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.Outcome measurements and statistical analysisOdds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.Results and limitationsLonger genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).ConclusionsOur investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.Patient summaryTelomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

Dataset Information

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

Publications

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

Similar Datasets

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