The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
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Xiaotian Yuan1,2,*, Guanghui Cheng2,*, Jingya Yu1, Shunzhen Zheng3, Chao Sun2, Qing Sun2, Kailin Li2, Zhaomin Lin2, Tiantian Liu4, Ping Li5, Yiteng Xu2, Feng Kong2, Magnus Bjorkholm1, Dawei Xu1
1Department of Medicine, Division of Hematology and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
2Central Research Laboratory, the Second Hospital of Shandong University, Jinan, PR China
3Department of OrganTransplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China
4Department of Pathology, Shandong University School of Medicine, Jinan, PR China
5School of Nursing, Shandong University, Jinan, PR China
*These authors contributed equally to this work
Feng Kong, email: [email protected]
Dawei Xu, email: [email protected]
Keywords: HCC, promoter mutations, rs2736098, rs2736100, SNP
Received: November 11, 2016 Accepted: February 07, 2017 Published: February 18, 2017
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.
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