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Genome-Wide Association Study Identifies a New Locus at 7q21.13 Associated with Hepatitis B Virus-Related Hepatocellular Carcinoma.

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机构: [1]State Key Laboratory of Proteomics, Beijing Proteome Research Center, BeijingInstitute of Radiation Medicine, Beijing, P.R. China [2]National EngineeringResearch Center for Protein Drugs, Beijing, P.R. China [3]National Center forProtein Sciences at Beijing, Beijing, P.R. China [4]Affiliated Cancer Hospital ofGuangxi Medical University, Nanning, Guangxi, P.R. China [5]State Key Laboratoryof Cancer Biology, Experimental Teaching Center of Basic Medicine, FourthMilitary Medical University, Xi'an, Shaanxi, P.R. China [6]Department of Gastroenterology,Zhongshan Hospital of Fudan University, Shanghai, P.R. China [7]Department of Pain Treatment, Tangdu Hospital, Fourth Military MedicalUniversity, Xi'an, Shaanxi, P.R. China [8]Department of Hepatobiliary Surgery,Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China [9]State Key Laboratory of Oncology in Southern China, Guangzhou, Guangdong,P.R. China [10]Department of Experimental Research, Sun Yat-Sen UniversityCancer Center, Guangzhou, Guangdong, P.R. China [11]Key Laboratory for MolecularGenetic Mechanisms and Intervention Research on High Altitude Disease ofTibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang,Shaanxi, P.R. China [12]Key Laboratory of High Altitude Environment andGenes Related to Diseases of Tibet Autonomous Region, School of Medicine,Xizang Minzu University, Xianyang, Shaanxi, P.R. China [13]Department of Epidemiologyand Biostatistics, Ministry of Education (MOE) Key Laboratory ofModernToxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu,P.R. China [14]Department of Surgical Oncology, Bayi Hospital Affiliated NanjingUniversity of Chinese Medicine, Nanjing, Jiangsu, P.R. China [15]Department ofOncology, Chengdu Military General Hospital, Chengdu, Sichuan, P.R. China.
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Purpose: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In China, chronic hepatitis B virus (HBV) infection remains the major risk factor for HCC. In this study, we performed a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci contributing to susceptibility to HBV-related HCC.Experimental Design: GWAS scan is performed in a collection of 205 HBV-related HCC trios (each trio includes an affected proband and his/her both parents), and 355 chronic HBV carriers with HCC (cases) and 360 chronic HBV carriers without HCC (controls), followed by two rounds of replication studies totally consisting of 3,796 cases and 2,544 controls.Results: We identified a novel association signal within the CDK14 gene at 7q21.13 (index rs10272859, OR = 1.28, P = 9.46 × 10-10). Furthermore, we observed that the at-risk rs10272859[G] allele was significantly associated with higher mRNA expression levels of CDK14 in liver tissues. Chromosome conformation capture assays in liver cells confirmed that a physical interaction exists between the promoter region of CDK14 and the risk-associated SNPs in strong linkage disequilibrium with the index rs10272859 at 7q21.13. This index rs10272859 also showed significant association with the survival of HCC patients.Conclusions: Our findings highlight a novel locus at 7q21.13 conferring both susceptibility and prognosis to HBV-related HCC, and suggest the CDK14 gene to be the functional target of the 7q21.13 locus. Clin Cancer Res; 24(4); 906-15. ©2017 AACR. ©2017 American Association for Cancer Research.

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大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
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Q1 ONCOLOGY
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Q1 ONCOLOGY

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第一作者机构: [1]State Key Laboratory of Proteomics, Beijing Proteome Research Center, BeijingInstitute of Radiation Medicine, Beijing, P.R. China [2]National EngineeringResearch Center for Protein Drugs, Beijing, P.R. China [3]National Center forProtein Sciences at Beijing, Beijing, P.R. China
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通讯机构: [1]State Key Laboratory of Proteomics, Beijing Proteome Research Center, BeijingInstitute of Radiation Medicine, Beijing, P.R. China [2]National EngineeringResearch Center for Protein Drugs, Beijing, P.R. China [3]National Center forProtein Sciences at Beijing, Beijing, P.R. China [*1]Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, P. R. China
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