Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Autor: Purdue MP; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. purduem@mail.nih.gov., Dutta D; Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Machiela MJ; Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Gorman BR; Booz Allen Hamilton Inc, McLean, VA, USA., Winter T; Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Okuhara D; Booz Allen Hamilton Inc, McLean, VA, USA., Cleland S; Booz Allen Hamilton Inc, McLean, VA, USA., Ferreiro-Iglesias A; Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France., Scheet P; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Liu A; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Wu C; Biosample Repository, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA., Antwi SO; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA., Larkin J; Department of Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK., Zequi SC; Department of Urology, A.C. Camargo Cancer Center, São Paulo, Brazil.; National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation INCIT-INOTE, São Paulo, Brazil.; Latin American Renal Cancer Group, São Paulo, Brazil.; Department of Surgery, Division of Urology, São Paulo Federal University, São Paulo, Brazil., Sun M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Hikino K; Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Hajiran A; Department of Urology, Division of Urologic Oncology, West Virginia University Cancer Institute, Morgantown, WV, USA., Lawson KA; Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Cárcano F; Department of Medical Oncology, Barretos Cancer Hospital, Barretos, Brazil., Blanchet O; Biobank Resource Centre, CHU Angers, Angers, France., Shuch B; Department of Urology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA., Nepple KG; Department of Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA., Margue G; Department of Urology, CHU Bordeaux, Bordeaux, France., Sundi D; Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA., Diver WR; Department of Population Science, American Cancer Society, Atlanta, GA, USA., Folgueira MAAK; Departments of Radiology and Oncology, Comprehensive Center for Precision Oncology-C2PO, Centro de Investigação Translacional em Oncologia, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas, Faculdade de Medicina Universidade de São Paulo, São Paulo, Brazil., van Bokhoven A; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Neffa F; Tumor Bank, Hospital Militar, Montevideo, Uruguay., Brown KM; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Hofmann JN; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Rhee J; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Yeager M; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA., Cole NR; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA., Hicks BD; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA., Manning MR; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA., Hutchinson AA; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA., Rothman N; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Huang WY; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Linehan WM; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Lori A; Department of Population Science, American Cancer Society, Atlanta, GA, USA., Ferragu M; Department of Urology, CHU Angers, Angers, France., Zidane-Marinnes M; Department of Pathology, CHU Angers, Angers, France., Serrano SV; Department of Medical Oncology, Barretos Cancer Hospital, Barretos, Brazil., Magnabosco WJ; Department of Urology, Barretos Cancer Hospital, Barretos, Brazil., Vilas A; Department of Pathology, Hospital Pasteur, Montevideo, Uruguay., Decia R; Department of Urology, Hospital Pasteur, Montevideo, Uruguay., Carusso F; Tumor Bank, Hospital Militar, Montevideo, Uruguay., Graham LS; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Anderson K; Oncology Clinical Research Support Team, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Bilen MA; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA., Arciero C; Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA., Pellegrin I; Biobank, Bordeaux Biothèque Santé, CHU Bordeaux, Bordeaux, France., Ricard S; Department of Urology, CHU Bordeaux, Bordeaux, France., Scelo G; Observational and Pragmatic Research Institute Pte Ltd, Singapore, Singapore., Banks RE; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK., Vasudev NS; Department of Oncology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK., Soomro N; Department of Urology, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK., Stewart GD; Department of Urology, Western General Hospital, NHS Lothian, Edinburgh, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Adeyoju A; Department of Urology, Stockport NHS Foundation Trust, Stockport, UK., Bromage S; Department of Urology, Stockport NHS Foundation Trust, Stockport, UK., Hrouda D; Department of Urology, Imperial College Healthcare NHS Trust, London, UK., Gibbons N; Department of Urology, Imperial College Healthcare NHS Trust, London, UK., Patel P; Division of Oncology, University of Nottingham, Nottingham, UK., Sullivan M; Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Protheroe A; Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Nugent FI; Department of Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA., Fournier MJ; Tissue Core, Moffitt Cancer Center, Tampa, FL, USA., Zhang X; Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Martin LJ; Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Komisarenko M; Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Eisen T; Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Cunningham SA; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Connolly DC; Cancer Signaling and Microenvironment, Biosample Repository Facility, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA., Uzzo RG; Department of Urology, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA., Zaridze D; Department of Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia., Mukeria A; Department of Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia., Holcatova I; Institute of Public Health and Preventive Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic.; Department of Oncology, Second Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic., Hornakova A; Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic., Foretova L; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic., Janout V; Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic., Mates D; Department of Occupational Health and Toxicology, National Center for Environmental Risk Monitoring, National Institute of Public Health, Bucharest, Romania., Jinga V; Urology Department, Academy of Romanian Scientists, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania., Rascu S; Urology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania., Mijuskovic M; Clinic of Nephrology, Faculty of Medicine, Military Medical Academy, Belgrade, Serbia., Savic S; Department of Urology, Clinical Hospital Center Dr Dragisa Misovic Dedinje, Belgrade, Serbia., Milosavljevic S; International Organisation for Cancer Prevention and Research, Belgrade, Serbia., Gaborieau V; Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France., Abedi-Ardekani B; Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France., McKay J; Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France., Johansson M; Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France., Phouthavongsy L; Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Hayman L; Diagnostic Development Program, Tissue Portal, Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Li J; Diagnostic Development Program, Tissue Portal, Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Lungu I; Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.; Diagnostic Development Program, Tissue Portal, Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Bezerra SM; Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil., Souza AG; Departments of Medical Imaging, Hematology and Oncology, Division of Medical Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Sares CTG; Departments of Surgery and Anatomy, Division of Urology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Reis RB; Departments of Surgery and Anatomy, Division of Urology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Gallucci FP; Surgery Department, Urology Division, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Cordeiro MD; Surgery Department, Urology Division, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Pomerantz M; Dana-Farber Cancer Institute, Boston, MA, USA., Lee GM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Freedman ML; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Dana-Farber Cancer Institute, Boston, MA, USA.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.; Broad Institute of MIT and Harvard, Boston, MA, USA., Jeong A; Department of Urology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA., Greenberg SE; Department of Population Sciences, Genetic Counseling Shared Resource, Huntsman Cancer Institute, Salt Lake City, UT, USA., Sanchez A; Department of Surgery, Division of Urology, Huntsman Cancer Institute and University of Utah, Salt Lake City, UT, USA., Thompson RH; Department of Urology, Mayo Clinic, Rochester, MN, USA., Sharma V; Department of Urology, Mayo Clinic, Rochester, MN, USA., Thiel DD; Department of Urology, Mayo Clinic, Jacksonville, FL, USA., Ball CT; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA., Abreu D; Department of Urology, Hospital Pasteur, Montevideo, Uruguay., Lam ET; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Nahas WC; Surgery Department, Urology Division, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Master VA; Department of Urology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA., Patel AV; Department of Population Science, American Cancer Society, Atlanta, GA, USA., Bernhard JC; Department of Urology, CHU Bordeaux, Bordeaux, France., Freedman ND; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Bigot P; Department of Urology, CHU Angers, Angers, France., Reis RM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal., Colli LM; Departament of Medical Image, Hematology and Oncology, Division of Medical Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Finelli A; Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Manley BJ; Genitourinary Oncology Program, Moffitt Cancer Center, Tampa, FL, USA., Terao C; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Choueiri TK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Carraro DM; Clinical and Functional Genomics Group, CIPE (International Research Center), A.C. Camargo Cancer Center, São Paulo, Brazil., Houlston R; Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK., Eckel-Passow JE; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Abbosh PH; Department of Nuclear Dynamics and Cancer, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA., Ganna A; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Brennan P; Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France., Gu J; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chanock SJ; Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. chanocks@mail.nih.gov.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2024 May; Vol. 56 (5), pp. 809-818. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.1038/s41588-024-01725-7
Abstrakt: 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.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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