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Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.
Purdue, Mark P; Dutta, Diptavo; Machiela, Mitchell J; Gorman, Bryan R; Winter, Timothy; Okuhara, Dayne; Cleland, Sara; Ferreiro-Iglesias, Aida; Scheet, Paul; Liu, Aoxing; Wu, Chao; Antwi, Samuel O; Larkin, James; Zequi, Stênio C; Sun, Maxine; Hikino, Keiko; Hajiran, Ali; Lawson, Keith A; Cárcano, Flavio; Blanchet, Odile; Shuch, Brian; Nepple, Kenneth G; Margue, Gaëlle; Sundi, Debasish; Diver, W Ryan; Folgueira, Maria A A K; van Bokhoven, Adrie; Neffa, Florencia; Brown, Kevin M; Hofmann, Jonathan N; Rhee, Jongeun; Yeager, Meredith; Cole, Nathan R; Hicks, Belynda D; Manning, Michelle R; Hutchinson, Amy A; Rothman, Nathaniel; Huang, Wen-Yi; Linehan, W Marston; Lori, Adriana; Ferragu, Matthieu; Zidane-Marinnes, Merzouka; Serrano, Sérgio V; Magnabosco, Wesley J; Vilas, Ana; Decia, Ricardo; Carusso, Florencia; Graham, Laura S; Anderson, Kyra; Bilen, Mehmet A.
Affiliation
  • 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.
  • Wu C; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Antwi SO; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Larkin J; Biosample Repository, Fox Chase Cancer Center-Temple Health, Philadelphia, PA, USA.
  • Zequi SC; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA.
  • Sun M; Department of Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK.
  • Hikino K; Department of Urology, A.C. Camargo Cancer Center, São Paulo, Brazil.
  • Hajiran A; National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation INCIT-INOTE, São Paulo, Brazil.
  • Lawson KA; Latin American Renal Cancer Group, São Paulo, Brazil.
  • Cárcano F; Department of Surgery, Division of Urology, São Paulo Federal University, São Paulo, Brazil.
  • Blanchet O; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Shuch B; Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Nepple KG; Department of Urology, Division of Urologic Oncology, West Virginia University Cancer Institute, Morgantown, WV, USA.
  • Margue G; Department of Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Sundi D; Department of Medical Oncology, Barretos Cancer Hospital, Barretos, Brazil.
  • Diver WR; Biobank Resource Centre, CHU Angers, Angers, France.
  • Folgueira MAAK; Department of Urology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
  • van Bokhoven A; Department of Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
  • Neffa F; Department of Urology, CHU Bordeaux, Bordeaux, France.
  • Brown KM; Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Hofmann JN; Department of Population Science, American Cancer Society, Atlanta, GA, USA.
  • Rhee J; 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.
  • Yeager M; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Cole NR; Tumor Bank, Hospital Militar, Montevideo, Uruguay.
  • Hicks BD; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Manning MR; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Hutchinson AA; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Rothman N; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA.
  • Huang WY; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA.
  • Linehan WM; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA.
  • Lori A; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA.
  • Ferragu M; Cancer Genomics Research Laboratory, Frederick National Laboratory, Rockville, MD, USA.
  • Zidane-Marinnes M; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Serrano SV; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Magnabosco WJ; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Vilas A; Department of Urology, CHU Angers, Angers, France.
  • Decia R; Department of Pathology, CHU Angers, Angers, France.
  • Carusso F; Department of Medical Oncology, Barretos Cancer Hospital, Barretos, Brazil.
  • Graham LS; Department of Urology, Barretos Cancer Hospital, Barretos, Brazil.
  • Bilen MA; Department of Pathology, Hospital Pasteur, Montevideo, Uruguay.
Nat Genet ; 56(5): 809-818, 2024 May.
Article in En | MEDLINE | ID: mdl-38671320
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Renal Cell / Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / Quantitative Trait Loci / Genome-Wide Association Study / Kidney Neoplasms Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2024 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Renal Cell / Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / Quantitative Trait Loci / Genome-Wide Association Study / Kidney Neoplasms Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2024 Type: Article Affiliation country: United States