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

Merzouka Zidane-Marinnes; Sérgio V Serrano; Wesley J Magnabosco; Ana Vilas; Ricardo Decia; Florencia Carusso; Laura S Graham; Kyra Anderson; Mehmet A Bilen; Cletus Arciero; Isabelle Pellegrin; Solène Ricard; Ghislaine Scelo; Rosamonde E Banks; Naveen S Vasudev; Naeem Soomro; Grant D Stewart; Adebanji Adeyoju; Stephen Bromage; David Hrouda; Brian Shuch; Sonia A Cunningham; Mark P Purdue; Kenneth G Nepple; Gaëlle Margue; Norma Gibbons; Debasish Sundi; Poulam Patel; Diptavo Dutta; W Ryan Diver; Maria A A K Folgueira; Chao Wu; Adrie van Bokhoven; Mitchell J Machiela; Florencia Neffa; Mark Sullivan; Samuel O Antwi; Kevin M Brown; Jonathan N Hofmann; Bryan R Gorman; Jongeun Rhee; Andrew Protheroe; Meredith Yeager; Denise C Connolly; Nathan R Cole; Timothy Winter; Belynda D Hicks; Francesca I Nugent; Michelle R Manning; James Larkin; Amy A Hutchinson; Michelle J Fournier; Nathaniel Rothman; Dayne Okuhara; Wen-Yi Huang; Robert G Uzzo; W Marston Linehan; Sara Cleland; Adriana Lori; Xiaoyu Zhang; Stênio C Zequi; Aida Ferreiro-Iglesias; Lisa J Martin; David Zaridze; Paul Scheet; Maria Komisarenko; Maxine Sun; Anush Mukeria; Aoxing Liu; Timothy Eisen; Keiko Hikino; Ivana Holcatova; Ali Hajiran; Anna Hornakova; Lenka Foretova; Keith A Lawson; Flavio Cárcano; Vladimir Janout; Odile Blanchet; Dana Mates; Viorel Jinga; Stefan Rascu; Mirjana Mijuskovic; Slavisa Savic; Sasa Milosavljevic; Valérie Gaborieau; Behnoush Abedi-Ardekani; James McKay; Mattias Johansson; Larry Phouthavongsy; Lindsay Hayman; Jason Li; Ilinca Lungu; Stephania M Bezerra; Aline G Souza; Claudia T G Sares; Rodolfo B Reis; Fabio P Gallucci; Mauricio D Cordeiro; Mark Pomerantz; Gwo-Shu M Lee; Matthew L Freedman; Anhyo Jeong; Samantha E Greenberg; Alejandro Sanchez; R Houston Thompson; Vidit Sharma; David D Thiel; Colleen T Ball; Diego Abreu; Elaine T Lam; William C Nahas; Viraj A Master; Alpa V Patel; Jean-Christophe Bernhard; Neal D Freedman; Pierre Bigot; Rui M Reis; Leandro M Colli; Antonio Finelli; Brandon J Manley; Chikashi Terao; Toni K Choueiri; Dirce M Carraro; Richard Houlston; Jeanette E Eckel-Passow; Philip H Abbosh; Andrea Ganna; Paul Brennan; Jian Gu; Stephen J Chanock; BioBank Japan Project

doi:10.1038/s41588-024-01725-7

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

Journal article

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

Merzouka Zidane-Marinnes, Sérgio V Serrano, Wesley J Magnabosco, Ana Vilas, Ricardo Decia, Florencia Carusso, Laura S Graham, Kyra Anderson, Mehmet A Bilen, Cletus Arciero, …

Nature genetics, Vol.56(5), pp.809-818

04/26/2024

DOI: 10.1038/s41588-024-01725-7

PMID: 38671320

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Abstract

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.

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Title: Subtitle: Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions
Creators: Merzouka Zidane-Marinnes - Centre Hospitalier Universitaire d'Angers
Sérgio V Serrano - Hospital de Câncer de Barretos
Wesley J Magnabosco - Hospital de Câncer de Barretos
Ana Vilas - Department of Pathology, Hospital Pasteur, Montevideo, Uruguay
Ricardo Decia - Department of Urology, Hospital Pasteur, Montevideo, Uruguay
Florencia Carusso - Hospital Militar Central
Laura S Graham - University of Colorado Anschutz Medical Campus
Kyra Anderson - University of Colorado Anschutz Medical Campus
Mehmet A Bilen - Winship Cancer Institute
Cletus Arciero - Winship Cancer Institute
Isabelle Pellegrin - Centre Hospitalier Universitaire de Bordeaux
Solène Ricard - Centre Hospitalier Universitaire de Bordeaux
Ghislaine Scelo - PragmatIC (United Kingdom)
Rosamonde E Banks - University of Leeds
Naveen S Vasudev - University of Leeds
Naeem Soomro - Newcastle upon Tyne Hospitals NHS Foundation Trust
Grant D Stewart - University of Cambridge
Adebanji Adeyoju - Stockport NHS Foundation Trust
Stephen Bromage - Stockport NHS Foundation Trust
David Hrouda - Imperial College Healthcare NHS Trust
Brian Shuch - UCLA Jonsson Comprehensive Cancer Center
Sonia A Cunningham - The University of Texas MD Anderson Cancer Center
Mark P Purdue - National Cancer Institute
Kenneth G Nepple - University of Iowa
Gaëlle Margue - Centre Hospitalier Universitaire de Bordeaux
Norma Gibbons - Imperial College Healthcare NHS Trust
Debasish Sundi - The Ohio State University Wexner Medical Center
Poulam Patel - University of Nottingham
Diptavo Dutta - National Cancer Institute
W Ryan Diver - American Cancer Society
Maria A A K Folgueira - Instituto do Câncer do Estado de São Paulo
Chao Wu - Fox Chase Cancer Center
Adrie van Bokhoven - University of Colorado Anschutz Medical Campus
Mitchell J Machiela - National Cancer Institute
Florencia Neffa - Hospital Militar Central
Mark Sullivan - University of Oxford
Samuel O Antwi - Mayo Clinic
Kevin M Brown - National Cancer Institute
Jonathan N Hofmann - National Cancer Institute
Bryan R Gorman - Booz Allen Hamilton (United States)
Jongeun Rhee - National Cancer Institute
Andrew Protheroe - University of Oxford
Meredith Yeager - Frederick National Laboratory for Cancer Research
Denise C Connolly - Fox Chase Cancer Center
Nathan R Cole - Frederick National Laboratory for Cancer Research
Timothy Winter - National Cancer Institute
Belynda D Hicks - Frederick National Laboratory for Cancer Research
Francesca I Nugent - Department of Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
Michelle R Manning - Frederick National Laboratory for Cancer Research
James Larkin - Royal Marsden NHS Foundation Trust
Amy A Hutchinson - Frederick National Laboratory for Cancer Research
Michelle J Fournier - Moffitt Cancer Center
Nathaniel Rothman - Division of Cancer Epidemiology and Genetics
Dayne Okuhara - Booz Allen Hamilton (United States)
Wen-Yi Huang - Division of Cancer Epidemiology and Genetics
Robert G Uzzo - Fox Chase Cancer Center
W Marston Linehan - National Cancer Institute
Sara Cleland - Booz Allen Hamilton (United States)
Adriana Lori - American Cancer Society
Xiaoyu Zhang - Princess Margaret Cancer Centre
Stênio C Zequi - Universidade de São Paulo
Aida Ferreiro-Iglesias - Centre international de recherche sur le cancer
Lisa J Martin - Princess Margaret Cancer Centre
David Zaridze - N&N Pharmaceuticals (United States)
Paul Scheet - The University of Texas MD Anderson Cancer Center
Maria Komisarenko - Princess Margaret Cancer Centre
Maxine Sun - Dana-Farber Cancer Institute
Anush Mukeria - N&N Pharmaceuticals (United States)
Aoxing Liu - Broad Institute
Timothy Eisen - Cambridge University Hospitals NHS Foundation Trust
Keiko Hikino - RIKEN Center for Integrative Medical Sciences
Ivana Holcatova - Charles University
Ali Hajiran - West Virginia University
Anna Hornakova - Charles University
Lenka Foretova - Masaryk Memorial Cancer Institute
Keith A Lawson - Princess Margaret Cancer Centre
Flavio Cárcano - Hospital de Câncer de Barretos
Vladimir Janout - Palacký University Olomouc
Odile Blanchet - Centre Hospitalier Universitaire d'Angers
Dana Mates - Department of Occupational Health and Toxicology, National Center for Environmental Risk Monitoring, National Institute of Public Health, Bucharest, Romania
Viorel Jinga - Carol Davila University of Medicine and Pharmacy
Stefan Rascu - Carol Davila University of Medicine and Pharmacy
Mirjana Mijuskovic - Military Medical Academy
Slavisa Savic - University Hospital Center Dr Dragiša Mišović
Sasa Milosavljevic - International Organisation for Cancer Prevention and Research, Belgrade, Serbia
Valérie Gaborieau - Centre international de recherche sur le cancer
Behnoush Abedi-Ardekani - Centre international de recherche sur le cancer
James McKay - Centre international de recherche sur le cancer
Mattias Johansson - Centre international de recherche sur le cancer
Larry Phouthavongsy - Ontario Institute for Cancer Research
Lindsay Hayman - Ontario Institute for Cancer Research
Jason Li - Ontario Institute for Cancer Research
Ilinca Lungu - Ontario Institute for Cancer Research
Stephania M Bezerra - AC Camargo Hospital
Aline G Souza - Universidade de São Paulo
Claudia T G Sares - Universidade de São Paulo
Rodolfo B Reis - Universidade de São Paulo
Fabio P Gallucci - Instituto do Câncer do Estado de São Paulo
Mauricio D Cordeiro - Instituto do Câncer do Estado de São Paulo
Mark Pomerantz - Dana-Farber Cancer Institute
Gwo-Shu M Lee - Dana-Farber Cancer Institute
Matthew L Freedman - Broad Institute
Anhyo Jeong - UCLA Jonsson Comprehensive Cancer Center
Samantha E Greenberg - Huntsman Cancer Institute
Alejandro Sanchez - University of Utah
R Houston Thompson - Mayo Clinic
Vidit Sharma - Mayo Clinic
David D Thiel - Mayo Clinic
Colleen T Ball - Mayo Clinic
Diego Abreu - Department of Urology, Hospital Pasteur, Montevideo, Uruguay
Elaine T Lam - University of Colorado Anschutz Medical Campus
William C Nahas - Instituto do Câncer do Estado de São Paulo
Viraj A Master - Winship Cancer Institute
Alpa V Patel - American Cancer Society
Jean-Christophe Bernhard - Centre Hospitalier Universitaire de Bordeaux
Neal D Freedman - Division of Cancer Epidemiology and Genetics
Pierre Bigot - Centre Hospitalier Universitaire d'Angers
Rui M Reis - University of Minho
Leandro M Colli - Universidade de São Paulo
Antonio Finelli - Princess Margaret Cancer Centre
Brandon J Manley - Moffitt Cancer Center
Chikashi Terao - RIKEN Center for Integrative Medical Sciences
Toni K Choueiri - Brigham and Women's Hospital
Dirce M Carraro - AC Camargo Hospital
Richard Houlston - Institute of Cancer Research
Jeanette E Eckel-Passow - Mayo Clinic
Philip H Abbosh - Fox Chase Cancer Center
Andrea Ganna - Broad Institute
Paul Brennan - Centre international de recherche sur le cancer
Jian Gu - The University of Texas MD Anderson Cancer Center
Stephen J Chanock - Division of Cancer Epidemiology and Genetics
BioBank Japan Project
Resource Type: Journal article
Publication Details: Nature genetics, Vol.56(5), pp.809-818
DOI: 10.1038/s41588-024-01725-7
PMID: 38671320
NLM abbreviation: Nat Genet
eISSN: 1546-1718
Language: English
Electronic publication date: 04/26/2024
Academic Unit: Urology
Record Identifier: 9984618625602771

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