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

Mark P Purdue^#¹, Diptavo Dutta^#², Mitchell J Machiela^#², Bryan R Gorman^#³, Timothy Winter⁴, Dayne Okuhara³, Sara Cleland³, Aida Ferreiro-Iglesias⁵, Paul Scheet⁶, Aoxing Liu^{7

8

9}, Chao Wu¹⁰, Samuel O Antwi¹¹, James Larkin¹², Stênio C Zequi^{13

14

15

16}, Maxine Sun¹⁷, Keiko Hikino¹⁸, Ali Hajiran¹⁹, Keith A Lawson²⁰, Flavio Cárcano²¹, Odile Blanchet²², Brian Shuch²³, Kenneth G Nepple²⁴, Gaëlle Margue²⁵, Debasish Sundi²⁶, W Ryan Diver²⁷, Maria A A K Folgueira²⁸, Adrie van Bokhoven²⁹, Florencia Neffa³⁰, Kevin M Brown³¹, Jonathan N Hofmann³², Jongeun Rhee³², Meredith Yeager³³, Nathan R Cole³³, Belynda D Hicks³³, Michelle R Manning³³, Amy A Hutchinson³³, Nathaniel Rothman³², Wen-Yi Huang³⁴, W Marston Linehan³⁵, Adriana Lori²⁷, Matthieu Ferragu³⁶, Merzouka Zidane-Marinnes³⁷, Sérgio V Serrano²¹, Wesley J Magnabosco³⁸; BioBank Japan Project; Ana Vilas³⁹, Ricardo Decia⁴⁰, Florencia Carusso³⁰, Laura S Graham⁴¹, Kyra Anderson⁴², Mehmet A Bilen⁴³, Cletus Arciero⁴⁴, Isabelle Pellegrin⁴⁵, Solène Ricard²⁵; FinnGen; Ghislaine Scelo⁴⁶, Rosamonde E Banks⁴⁷, Naveen S Vasudev⁴⁸, Naeem Soomro⁴⁹, Grant D Stewart^{50

51}, Adebanji Adeyoju⁵², Stephen Bromage⁵², David Hrouda⁵³, Norma Gibbons⁵³, Poulam Patel⁵⁴, Mark Sullivan⁵⁵, Andrew Protheroe⁵⁶, Francesca I Nugent²⁴, Michelle J Fournier⁵⁷, Xiaoyu Zhang²⁰, Lisa J Martin²⁰, Maria Komisarenko²⁰, Timothy Eisen⁵⁸, Sonia A Cunningham⁶, Denise C Connolly⁵⁹, Robert G Uzzo⁶⁰, David Zaridze⁶¹, Anush Mukeria⁶¹, Ivana Holcatova^{62

63}, Anna Hornakova⁶⁴, Lenka Foretova⁶⁵, Vladimir Janout⁶⁶, Dana Mates⁶⁷, Viorel Jinga⁶⁸, Stefan Rascu⁶⁹, Mirjana Mijuskovic⁷⁰, Slavisa Savic⁷¹, Sasa Milosavljevic⁷², Valérie Gaborieau⁵, Behnoush Abedi-Ardekani⁵, James McKay⁵, Mattias Johansson⁵, Larry Phouthavongsy⁷³, Lindsay Hayman⁷⁴, Jason Li⁷⁴, Ilinca Lungu^{73

74}, Stephania M Bezerra⁷⁵, Aline G Souza⁷⁶, Claudia T G Sares⁷⁷, Rodolfo B Reis⁷⁷, Fabio P Gallucci⁷⁸, Mauricio D Cordeiro⁷⁸, Mark Pomerantz⁷⁹, Gwo-Shu M Lee¹⁷, Matthew L Freedman^{17

79

80

81}, Anhyo Jeong²³, Samantha E Greenberg⁸², Alejandro Sanchez⁸³, R Houston Thompson⁸⁴, Vidit Sharma⁸⁴, David D Thiel⁸⁵, Colleen T Ball¹¹, Diego Abreu⁴⁰, Elaine T Lam⁴¹, William C Nahas⁷⁸, Viraj A Master⁸⁶, Alpa V Patel²⁷, Jean-Christophe Bernhard²⁵, Neal D Freedman³⁴, Pierre Bigot³⁶, Rui M Reis^{87

88}, Leandro M Colli⁸⁹, Antonio Finelli²⁰, Brandon J Manley⁹⁰, Chikashi Terao⁹¹, Toni K Choueiri^{17

92}, Dirce M Carraro⁹³, Richard Houlston⁹⁴, Jeanette E Eckel-Passow⁹⁵, Philip H Abbosh⁹⁶, Andrea Ganna^{7

8

9}, Paul Brennan⁵, Jian Gu⁶, Stephen J Chanock⁹⁷

Affiliations

¹ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. purduem@mail.nih.gov.
² Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³ Booz Allen Hamilton Inc, McLean, VA, USA.
⁴ Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
⁵ Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
⁶ Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
⁸ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁹ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Biosample Repository, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
¹¹ Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA.
¹² Department of Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK.
¹³ Department of Urology, A.C. Camargo Cancer Center, São Paulo, Brazil.
¹⁴ National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation INCIT-INOTE, São Paulo, Brazil.
¹⁵ Latin American Renal Cancer Group, São Paulo, Brazil.
¹⁶ Department of Surgery, Division of Urology, São Paulo Federal University, São Paulo, Brazil.
¹⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁸ Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁹ Department of Urology, Division of Urologic Oncology, West Virginia University Cancer Institute, Morgantown, WV, USA.
²⁰ Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
²¹ Department of Medical Oncology, Barretos Cancer Hospital, Barretos, Brazil.
²² Biobank Resource Centre, CHU Angers, Angers, France.
²³ Department of Urology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
²⁴ Department of Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
²⁵ Department of Urology, CHU Bordeaux, Bordeaux, France.
²⁶ Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
²⁷ Department of Population Science, American Cancer Society, Atlanta, GA, USA.
²⁸ 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.
²⁹ Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³⁰ Tumor Bank, Hospital Militar, Montevideo, Uruguay.
³¹ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³² Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³³ Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA.
³⁴ Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³⁵ Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
³⁶ Department of Urology, CHU Angers, Angers, France.
³⁷ Department of Pathology, CHU Angers, Angers, France.
³⁸ Department of Urology, Barretos Cancer Hospital, Barretos, Brazil.
³⁹ Department of Pathology, Hospital Pasteur, Montevideo, Uruguay.
⁴⁰ Department of Urology, Hospital Pasteur, Montevideo, Uruguay.
⁴¹ Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴² Oncology Clinical Research Support Team, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴³ Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁴⁴ Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁴⁵ Biobank, Bordeaux Biothèque Santé, CHU Bordeaux, Bordeaux, France.
⁴⁶ Observational and Pragmatic Research Institute Pte Ltd, Singapore, Singapore.
⁴⁷ Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
⁴⁸ Department of Oncology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
⁴⁹ Department of Urology, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK.
⁵⁰ Department of Urology, Western General Hospital, NHS Lothian, Edinburgh, UK.
⁵¹ Department of Surgery, University of Cambridge, Cambridge, UK.
⁵² Department of Urology, Stockport NHS Foundation Trust, Stockport, UK.
⁵³ Department of Urology, Imperial College Healthcare NHS Trust, London, UK.
⁵⁴ Division of Oncology, University of Nottingham, Nottingham, UK.
⁵⁵ Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵⁶ Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵⁷ Tissue Core, Moffitt Cancer Center, Tampa, FL, USA.
⁵⁸ Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁵⁹ Cancer Signaling and Microenvironment, Biosample Repository Facility, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
⁶⁰ Department of Urology, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
⁶¹ Department of Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia.
⁶² Institute of Public Health and Preventive Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
⁶³ Department of Oncology, Second Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.
⁶⁴ Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
⁶⁵ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁶⁶ Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
⁶⁷ Department of Occupational Health and Toxicology, National Center for Environmental Risk Monitoring, National Institute of Public Health, Bucharest, Romania.
⁶⁸ Urology Department, Academy of Romanian Scientists, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
⁶⁹ Urology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
⁷⁰ Clinic of Nephrology, Faculty of Medicine, Military Medical Academy, Belgrade, Serbia.
⁷¹ Department of Urology, Clinical Hospital Center Dr Dragisa Misovic Dedinje, Belgrade, Serbia.
⁷² International Organisation for Cancer Prevention and Research, Belgrade, Serbia.
⁷³ Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
⁷⁴ Diagnostic Development Program, Tissue Portal, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
⁷⁵ Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil.
⁷⁶ Departments of Medical Imaging, Hematology and Oncology, Division of Medical Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
⁷⁷ Departments of Surgery and Anatomy, Division of Urology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
⁷⁸ 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.
⁷⁹ Dana-Farber Cancer Institute, Boston, MA, USA.
⁸⁰ Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸¹ Broad Institute of MIT and Harvard, Boston, MA, USA.
⁸² Department of Population Sciences, Genetic Counseling Shared Resource, Huntsman Cancer Institute, Salt Lake City, UT, USA.
⁸³ Department of Surgery, Division of Urology, Huntsman Cancer Institute and University of Utah, Salt Lake City, UT, USA.
⁸⁴ Department of Urology, Mayo Clinic, Rochester, MN, USA.
⁸⁵ Department of Urology, Mayo Clinic, Jacksonville, FL, USA.
⁸⁶ Department of Urology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁸⁷ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
⁸⁸ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
⁸⁹ Departament of Medical Image, Hematology and Oncology, Division of Medical Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
⁹⁰ Genitourinary Oncology Program, Moffitt Cancer Center, Tampa, FL, USA.
⁹¹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁹² Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁹³ Clinical and Functional Genomics Group, CIPE (International Research Center), A.C. Camargo Cancer Center, São Paulo, Brazil.
⁹⁴ Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
⁹⁵ Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
⁹⁶ Department of Nuclear Dynamics and Cancer, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
⁹⁷ Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. chanocks@mail.nih.gov.

^# Contributed equally.

PMID: 38671320
DOI: 10.1038/s41588-024-01725-7

Meta-Analysis

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

Mark P Purdue et al. Nat Genet. 2024 May.

. 2024 May;56(5):809-818.

doi: 10.1038/s41588-024-01725-7. Epub 2024 Apr 26.

Authors

Affiliations

¹ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. purduem@mail.nih.gov.
² Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³ Booz Allen Hamilton Inc, McLean, VA, USA.
⁴ Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
⁵ Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
⁶ Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
⁸ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁹ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Biosample Repository, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
¹¹ Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA.
¹² Department of Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK.
¹³ Department of Urology, A.C. Camargo Cancer Center, São Paulo, Brazil.
¹⁴ National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation INCIT-INOTE, São Paulo, Brazil.
¹⁵ Latin American Renal Cancer Group, São Paulo, Brazil.
¹⁶ Department of Surgery, Division of Urology, São Paulo Federal University, São Paulo, Brazil.
¹⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁸ Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁹ Department of Urology, Division of Urologic Oncology, West Virginia University Cancer Institute, Morgantown, WV, USA.
²⁰ Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
²¹ Department of Medical Oncology, Barretos Cancer Hospital, Barretos, Brazil.
²² Biobank Resource Centre, CHU Angers, Angers, France.
²³ Department of Urology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
²⁴ Department of Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
²⁵ Department of Urology, CHU Bordeaux, Bordeaux, France.
²⁶ Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
²⁷ Department of Population Science, American Cancer Society, Atlanta, GA, USA.
²⁸ 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.
²⁹ Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³⁰ Tumor Bank, Hospital Militar, Montevideo, Uruguay.
³¹ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³² Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³³ Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA.
³⁴ Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³⁵ Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
³⁶ Department of Urology, CHU Angers, Angers, France.
³⁷ Department of Pathology, CHU Angers, Angers, France.
³⁸ Department of Urology, Barretos Cancer Hospital, Barretos, Brazil.
³⁹ Department of Pathology, Hospital Pasteur, Montevideo, Uruguay.
⁴⁰ Department of Urology, Hospital Pasteur, Montevideo, Uruguay.
⁴¹ Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴² Oncology Clinical Research Support Team, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴³ Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁴⁴ Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁴⁵ Biobank, Bordeaux Biothèque Santé, CHU Bordeaux, Bordeaux, France.
⁴⁶ Observational and Pragmatic Research Institute Pte Ltd, Singapore, Singapore.
⁴⁷ Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
⁴⁸ Department of Oncology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
⁴⁹ Department of Urology, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK.
⁵⁰ Department of Urology, Western General Hospital, NHS Lothian, Edinburgh, UK.
⁵¹ Department of Surgery, University of Cambridge, Cambridge, UK.
⁵² Department of Urology, Stockport NHS Foundation Trust, Stockport, UK.
⁵³ Department of Urology, Imperial College Healthcare NHS Trust, London, UK.
⁵⁴ Division of Oncology, University of Nottingham, Nottingham, UK.
⁵⁵ Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵⁶ Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵⁷ Tissue Core, Moffitt Cancer Center, Tampa, FL, USA.
⁵⁸ Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁵⁹ Cancer Signaling and Microenvironment, Biosample Repository Facility, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
⁶⁰ Department of Urology, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
⁶¹ Department of Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia.
⁶² Institute of Public Health and Preventive Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
⁶³ Department of Oncology, Second Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.
⁶⁴ Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
⁶⁵ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁶⁶ Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
⁶⁷ Department of Occupational Health and Toxicology, National Center for Environmental Risk Monitoring, National Institute of Public Health, Bucharest, Romania.
⁶⁸ Urology Department, Academy of Romanian Scientists, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
⁶⁹ Urology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
⁷⁰ Clinic of Nephrology, Faculty of Medicine, Military Medical Academy, Belgrade, Serbia.
⁷¹ Department of Urology, Clinical Hospital Center Dr Dragisa Misovic Dedinje, Belgrade, Serbia.
⁷² International Organisation for Cancer Prevention and Research, Belgrade, Serbia.
⁷³ Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
⁷⁴ Diagnostic Development Program, Tissue Portal, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
⁷⁵ Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil.
⁷⁶ Departments of Medical Imaging, Hematology and Oncology, Division of Medical Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
⁷⁷ Departments of Surgery and Anatomy, Division of Urology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
⁷⁸ 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.
⁷⁹ Dana-Farber Cancer Institute, Boston, MA, USA.
⁸⁰ Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸¹ Broad Institute of MIT and Harvard, Boston, MA, USA.
⁸² Department of Population Sciences, Genetic Counseling Shared Resource, Huntsman Cancer Institute, Salt Lake City, UT, USA.
⁸³ Department of Surgery, Division of Urology, Huntsman Cancer Institute and University of Utah, Salt Lake City, UT, USA.
⁸⁴ Department of Urology, Mayo Clinic, Rochester, MN, USA.
⁸⁵ Department of Urology, Mayo Clinic, Jacksonville, FL, USA.
⁸⁶ Department of Urology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁸⁷ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
⁸⁸ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
⁸⁹ Departament of Medical Image, Hematology and Oncology, Division of Medical Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
⁹⁰ Genitourinary Oncology Program, Moffitt Cancer Center, Tampa, FL, USA.
⁹¹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁹² Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁹³ Clinical and Functional Genomics Group, CIPE (International Research Center), A.C. Camargo Cancer Center, São Paulo, Brazil.
⁹⁴ Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
⁹⁵ Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
⁹⁶ Department of Nuclear Dynamics and Cancer, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
⁹⁷ Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. chanocks@mail.nih.gov.

^# Contributed equally.

PMID: 38671320
DOI: 10.1038/s41588-024-01725-7

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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References

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

Affiliations

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

Authors

Affiliations

Abstract

References

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Grants and funding

LinkOut - more resources

Full Text Sources

Medical