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Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases

Author

Listed:
  • Jonathan Mitchell

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Niedzica Camacho

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Patrick Shea

    (Columbia University)

  • Konrad H. Stopsack

    (Massachusetts General Hospital and Harvard Medical School
    Harvard T. H. Chan School of Public Health)

  • Vijai Joseph

    (Sloan Kettering Institute
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Oliver S. Burren

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Ryan S. Dhindsa

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca
    Baylor College of Medicine)

  • Abhishek Nag

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Jacob E. Berchuck

    (Dana-Farber Cancer Institute)

  • Amanda O’Neill

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Ali Abbasi

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Anthony W. Zoghbi

    (Baylor College of Medicine)

  • Jesus Alegre-Díaz

    (National Autonomous University of Mexico, Copilco Universidad)

  • Pablo Kuri-Morales

    (National Autonomous University of Mexico, Copilco Universidad
    Instituto Tecnológico y de Estudios Superiores de Monterrey, Tecnológico)

  • Jaime Berumen

    (National Autonomous University of Mexico, Copilco Universidad)

  • Roberto Tapia-Conyer

    (National Autonomous University of Mexico, Copilco Universidad)

  • Jonathan Emberson

    (University of Oxford)

  • Jason M. Torres

    (University of Oxford)

  • Rory Collins

    (University of Oxford)

  • Quanli Wang

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • David Goldstein

    (Columbia University)

  • Athena Matakidou

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Carolina Haefliger

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Lauren Anderson-Dring

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Ruth March

    (AstraZeneca)

  • Vaidehi Jobanputra

    (Columbia University
    Columbia University)

  • Brian Dougherty

    (AstraZeneca)

  • Keren Carss

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Slavé Petrovski

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca)

  • Philip W. Kantoff

    (Memorial Sloan Kettering Cancer Center
    Convergent Therapeutics)

  • Kenneth Offit

    (Sloan Kettering Institute
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Lorelei A. Mucci

    (Harvard T. H. Chan School of Public Health
    American Cancer Society)

  • Mark Pomerantz

    (Dana-Farber Cancer Institute)

  • Margarete A. Fabre

    (Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

Abstract

To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis of 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline whole exome or genome sequencing data, and one cohort with imputed array data. At the gene level, our case-control collapsing analysis confirms associations between rare damaging variants in four genes and increased prostate cancer risk: SAMHD1, BRCA2 and ATM at the study-wide significance level (P

Suggested Citation

  • Jonathan Mitchell & Niedzica Camacho & Patrick Shea & Konrad H. Stopsack & Vijai Joseph & Oliver S. Burren & Ryan S. Dhindsa & Abhishek Nag & Jacob E. Berchuck & Amanda O’Neill & Ali Abbasi & Anthony , 2025. "Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56944-1
    DOI: 10.1038/s41467-025-56944-1
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    References listed on IDEAS

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