The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
| Autor: | Ping Li, Tiantian Liu, Feng Kong, Guanghui Cheng, Qing Sun, Jingya Yu, Shunzhen Zheng, Magnus Björkholm, Chao Sun, Dawei Xu, Kailin Li, Yiteng Xu, Xiaotian Yuan, Zhaomin Lin |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Telomerase Carcinoma Hepatocellular SNP Single-nucleotide polymorphism Polymorphism Single Nucleotide Germline 03 medical and health sciences 0302 clinical medicine Germline mutation Gene Frequency rs2736098 Genotype Humans Medicine Genetic Predisposition to Disease Telomerase reverse transcriptase HCC Promoter Regions Genetic Germ-Line Mutation Aged Genetics business.industry Incidence Liver Neoplasms Cancer Middle Aged HCCS medicine.disease Molecular biology rs2736100 030104 developmental biology Oncology Case-Control Studies 030220 oncology & carcinogenesis promoter mutations Female business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.15498 |
| Popis: | Telomerase activation via induction of the catalytic component telomerase reverse transcriptase (TERT) plays essential roles in malignant transformation. TERT promoter-activating mutations were recently identified as a novel mechanism to activate telomerase in hepatocellular carcinoma (HCC) and many other malignancies. In addition, single nucleotide polymorphisms (SNPs) in the TERT rs2736098 and rs2736100 are significantly associated with cancer susceptibility. It is currently unclear whether different germline TERT variants modify TERT promoter mutations. Here we analyzed the TERT promoter status and genotyped the TERT SNPs at rs2736098 and rs2736100 in patients with HCC. Thirty percent of HCCs harbored TERT promoter mutations and there was a significant difference in rs2736098 and rs2736100 genotypes between wt and mutant TERT promoter-bearing HCC tumors (P = 0.007 and 0.018, respectively). For rs2736100, the cancer risk genotype CC was significantly associated with a reduced incidence of TERT promoter mutations compared to AA + AC variants [Odds ratio (OR): 0.181, 95% Confidence interval (CI): 0.0543–0.601, P = 0.004]. The rs2736098_CT genotype was significantly associated with the TERT promoter mutation-positive tumors compared to the TT genotype (OR: 5.391, 95% CI: 1.234–23.553, P = 0.025). These differences in genotype distribution did not differ between patients with a wt TERT promoter and controls. The presence of TERT promoter mutations was not associated with clinico-pathological variables. Taken together, the germline TERT genetic background may significantly affect the onset of TERT promoter mutations in HCCs, which provides a better understanding of HCC-related TERT promoter mutations and telomerase regulation in cancer. |
| Databáze: | OpenAIRE |
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