Karina Dalsgaard Sørensen

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperLetterResearchpeer-review

  • Fredrick R Schumacher, Seidman Cancer Center, University Hospitals, Cleveland, OH, USA. frs2@case.edu.
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  • Ali Amin Al Olama, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. aa461@medschl.cam.ac.uk.
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  • Sonja I Berndt, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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  • Sara Benlloch, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Mahbubl Ahmed, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Edward J Saunders, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Tokhir Dadaev, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Daniel Leongamornlert, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Ezequiel Anokian, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Clara Cieza-Borrella, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Chee Goh, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Mark N Brook, Division of Breast Cancer Research, The Institute of Cancer Research, London, England.
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  • Xin Sheng, Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
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  • Laura Fachal, Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, Cambridge, CB1 8RN, UK.
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  • Joe Dennis, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
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  • Jonathan Tyrer, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
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  • Kenneth Muir, Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
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  • Artitaya Lophatananon, Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
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  • Victoria L Stevens, Epidemiology Research Program, American Cancer Society, Atlanta, USA
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  • Susan M Gapstur, Epidemiology Research Program, American Cancer Society, Atlanta, USA
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  • Brian D Carter, Epidemiology Research Program, American Cancer Society, Atlanta, USA
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  • Catherine M Tangen, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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  • Phyllis J Goodman, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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  • Ian M Thompson, CHRISTUS Santa Rosa Hospital-Medical Center, San Antonio, TX, USA.
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  • Jyotsna Batra, Australian Prostate Cancer Research Centre-QLD, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
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  • Suzanne Chambers, Cancer Council Queensland, 553 Gregory Tce, Fortitude Valley, QLD 4006, Australia. Electronic address: dannyyoulden@cancerqld.org.au.
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  • Leire Moya, Australian Prostate Cancer Research Centre-QLD, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
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  • Judith Clements, Australian Prostate Cancer Research Centre-QLD, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
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  • Lisa Horvath, Department of Endocrinology, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia.
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  • Wayne Tilley, Dame Roma Mitchell Cancer Research Centre, University of Adelaide, Adelaide, South Australia, Australia.
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  • Gail P Risbridger, Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.
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  • Henrik Gronberg, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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  • Markus Aly, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
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  • Tobias Nordström, Department of Clinical Sciences at Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden.
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  • Paul Pharoah, Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, Cambridge, CB1 8RN, UK.
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  • Nora Pashayan, Department of Applied Health Research, University College London, UK.
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  • Johanna Schleutker, Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, Turku, Finland.
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  • Teuvo L J Tammela, Department of Urology, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
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  • Csilla Sipeky, Institute of Biomedicine, University of Turku, Turku, Finland.
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  • Anssi Auvinen, Department of Epidemiology, School of Health Sciences, University of Tampere, Tampere, Finland.
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  • Demetrius Albanes, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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  • Stephanie Weinstein, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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  • Alicja Wolk, Department of Surgical Sciences, Uppsala University, Uppsala, 75185, Sweden.
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  • Karina Dalsgaard Sorensen
  • Torben Falck Orntoft
  • Michael Borre
  • Profile Study

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .

Original languageEnglish
JournalNature Genetics
Volume50
Issue7
Pages (from-to)928-936
Number of pages9
ISSN1061-4036
DOIs
Publication statusPublished - Jul 2018

    Research areas

  • BIOLOGICAL PATHWAYS, DISEASE, FAMILY-HISTORY, GENE, GENOME-WIDE ASSOCIATION, IDENTIFICATION, METAANALYSIS, MULTIPLE LOCI, RISK, VARIANTS

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