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Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions
MP. Purdue, D. Dutta, MJ. Machiela, BR. Gorman, T. Winter, D. Okuhara, S. Cleland, A. Ferreiro-Iglesias, P. Scheet, A. Liu, C. Wu, SO. Antwi, J. Larkin, SC. Zequi, M. Sun, K. Hikino, A. Hajiran, KA. Lawson, F. Cárcano, O. Blanchet, B. Shuch, KG....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, metaanalýza
Grantová podpora
001
World Health Organization - International
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- běloši genetika MeSH
- celogenomová asociační studie * MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus * MeSH
- karcinom z renálních buněk * genetika MeSH
- lidé MeSH
- lokus kvantitativního znaku * MeSH
- nádorový supresorový protein VHL genetika MeSH
- nádory ledvin * genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.
Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA
Biobank Bordeaux Biothèque Santé CHU Bordeaux Bordeaux France
Biobank Resource Centre CHU Angers Angers France
Biosample Repository Fox Chase Cancer Center Temple Health Philadelphia PA USA
Booz Allen Hamilton Inc McLean VA USA
Broad Institute of MIT and Harvard Boston MA USA
Cancer Genomics Research Laboratory Frederick National Laboratory Rockville MD USA
Center for Functional Cancer Epigenetics Dana Farber Cancer Institute Boston MA USA
Clinic of Nephrology Faculty of Medicine Military Medical Academy Belgrade Serbia
Clinical and Functional Genomics Group CIPE A C Camargo Cancer Center São Paulo Brazil
Dana Farber Cancer Institute Boston MA USA
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Medical Oncology Barretos Cancer Hospital Barretos Brazil
Department of Medical Oncology Dana Farber Cancer Institute Boston MA USA
Department of Medical Oncology Royal Marsden NHS Foundation Trust London UK
Department of Medicine Brigham and Women's Hospital Boston MA USA
Department of Nuclear Dynamics and Cancer Fox Chase Cancer Center Temple Health Philadelphia PA USA
Department of Oncology Cambridge University Hospitals NHS Foundation Trust Cambridge UK
Department of Oncology Oxford University Hospitals NHS Foundation Trust Oxford UK
Department of Pathology A C Camargo Cancer Center São Paulo Brazil
Department of Pathology CHU Angers Angers France
Department of Pathology Hospital Pasteur Montevideo Uruguay
Department of Pathology University of Colorado Anschutz Medical Campus Aurora CO USA
Department of Population Science American Cancer Society Atlanta GA USA
Department of Quantitative Health Sciences Mayo Clinic Jacksonville FL USA
Department of Quantitative Health Sciences Mayo Clinic Rochester MN USA
Department of Surgery Division of Urology São Paulo Federal University São Paulo Brazil
Department of Surgery University of Cambridge Cambridge UK
Department of Surgery Winship Cancer Institute Emory University School of Medicine Atlanta GA USA
Department of Urology A C Camargo Cancer Center São Paulo Brazil
Department of Urology Barretos Cancer Hospital Barretos Brazil
Department of Urology CHU Angers Angers France
Department of Urology CHU Bordeaux Bordeaux France
Department of Urology Clinical Hospital Center Dr Dragisa Misovic Dedinje Belgrade Serbia
Department of Urology Fox Chase Cancer Center Temple Health Philadelphia PA USA
Department of Urology Holden Comprehensive Cancer Center University of Iowa Iowa City IA USA
Department of Urology Hospital Pasteur Montevideo Uruguay
Department of Urology Imperial College Healthcare NHS Trust London UK
Department of Urology Mayo Clinic Jacksonville FL USA
Department of Urology Mayo Clinic Rochester MN USA
Department of Urology Newcastle Hospitals NHS Foundation Trust Newcastle UK
Department of Urology Oxford University Hospitals NHS Foundation Trust Oxford UK
Department of Urology Stockport NHS Foundation Trust Stockport UK
Department of Urology The Ohio State University Wexner Medical Center Columbus OH USA
Department of Urology UCLA Jonsson Comprehensive Cancer Center Los Angeles CA USA
Department of Urology Western General Hospital NHS Lothian Edinburgh UK
Department of Urology Winship Cancer Institute Emory University School of Medicine Atlanta GA USA
Division of Genetics and Epidemiology Institute of Cancer Research Sutton UK
Division of Oncology University of Nottingham Nottingham UK
Faculty of Health Sciences Palacky University Olomouc Czech Republic
Genitourinary Oncology Program Moffitt Cancer Center Tampa FL USA
Genomic Epidemiology Branch International Agency for Research on Cancer Lyon France
Institute for Molecular Medicine Finland University of Helsinki Helsinki Finland
International Organisation for Cancer Prevention and Research Belgrade Serbia
Laboratory for Pharmacogenomics RIKEN Center for Integrative Medical Sciences Yokohama Japan
Latin American Renal Cancer Group São Paulo Brazil
Leeds Institute of Medical Research at St James's University of Leeds Leeds UK
Life and Health Sciences Research Institute School of Medicine University of Minho Braga Portugal
Molecular Oncology Research Center Barretos Cancer Hospital Barretos Brazil
Observational and Pragmatic Research Institute Pte Ltd Singapore Singapore
Oncology Clinical Research Support Team University of Colorado Anschutz Medical Campus Aurora CO USA
Ontario Tumour Bank Ontario Institute for Cancer Research Toronto Ontario Canada
Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA
Tissue Core Moffitt Cancer Center Tampa FL USA
Tumor Bank Hospital Militar Montevideo Uruguay
Urologic Oncology Branch Center for Cancer Research National Cancer Institute Bethesda MD USA
Urology Department Carol Davila University of Medicine and Pharmacy Bucharest Romania
Citace poskytuje Crossref.org
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