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Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men

Prostate Cancer and Prostatic Diseases volume 24, pages 845–851 (2021)Cite this article

Subjects

Abstract

Background

Clinical variables—age, family history, genetics—are used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores are associated with all prostate cancer (not specific for fatal cancers), PHS46 was also associated with age at prostate cancer death. We evaluated if adding PHS to clinical variables improves associations with prostate cancer death.

Methods

Genotype/phenotype data were obtained from a nested case–control Cohort of Swedish Men (n = 3279; 2163 with prostate cancer, 278 prostate cancer deaths). PHS and clinical variables (family history, alcohol intake, smoking, heart disease, hypertension, diabetes, body mass index) were tested via univariable Cox proportional hazards models for association with age at prostate cancer death. Multivariable Cox models with/without PHS were compared with log-likelihood tests.

Results

Median age at last follow-up/prostate cancer death was 78.0 (IQR: 72.3–84.1) and 81.4 (75.4–86.3) years, respectively. On univariable analysis, PHS46 (HR 3.41 [95% CI 2.78–4.17]), family history (HR 1.72 [1.46–2.03]), alcohol (HR 1.74 [1.40–2.15]), diabetes (HR 0.53 [0.37–0.75]) were each associated with prostate cancer death. On multivariable analysis, PHS46 (HR 2.45 [1.99–2.97]), family history (HR 1.73 [1.48–2.03]), alcohol (HR 1.45 [1.19–1.76]), diabetes (HR 0.62 [0.42–0.90]) all remained associated with fatal disease. Including PHS46 or PHS166 improved multivariable models for fatal prostate cancer (p < 10–15).

Conclusions

PHS had the most robust association with fatal prostate cancer in a multivariable model with common risk factors, including family history. Adding PHS to clinical variables may improve prostate cancer risk stratification strategies.

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Data availability

Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) Consortium data are available upon request to the Data Access Committee (http://practical.icr.ac.uk/blog/?page_id=135). Questions and requests for further information may be directed to PRACTICAL@icr.ac.uk.

Code availability

Code used for this work is stored in an institutional repository and will be shared upon request to the corresponding author.

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Funding

This study was funded in part by grants from the University of California (#C21CR2060), the United States National Institute of Health/National Institute of Biomedical Imaging and Bioengineering (#K08EB026503), the Research Council of Norway (#223273), KG Jebsen Stiftelsen, and South East Norway Health Authority. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies, who had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Division of Radiation Oncology, George Washington University, Washington, DC, USA

    Minh-Phuong Huynh-Le

  2. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA

    Roshan Karunamuni, Karen Tye & Tyler M. Seibert

  3. Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA

    Roshan Karunamuni, Chun Chieh Fan, Anders M. Dale & Tyler M. Seibert

  4. Division of Biostatistics and Halicioğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA

    Wesley K. Thompson

  5. Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA

    Wesley K. Thompson

  6. Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK

    Kenneth Muir & Artitaya Lophatananon

  7. Warwick Medical School, University of Warwick, Coventry, UK

    Kenneth Muir

  8. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Alicja Wolk & Niclas Håkansson

  9. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

    Alicja Wolk

  10. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

    Ian G. Mills

  11. NORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway

    Ole A. Andreassen

  12. Department of Radiology, University of California San Diego, La Jolla, CA, USA

    Anders M. Dale & Tyler M. Seibert

  13. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

    Tyler M. Seibert

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  1. Minh-Phuong Huynh-Le
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on behalf of The PRACTICAL Consortium

Corresponding author

Correspondence to Tyler M. Seibert.

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Conflict of interest

TMS reports honoraria from Multimodal Imaging Services Corporation for imaging segmentation and honoraria from Varian Medical Systems and WebMD, Inc. for educational content. AMD has additional disclosures outside the present work: founder, equity holder, and advisory board member for CorTechs Labs, Inc.; advisory board member of Human Longevity, Inc.; recipient of nonfinancial research support from General Electric Healthcare. CCF is a scientific consultant for CorTechs Labs, Inc.

Ethics approval

All contributing studies were approved by the relevant ethics committees and performed in accordance with the Declaration of Helsinki; written informed consent was obtained from the study participants. The present analyses used de-identified data from the PRACTICAL consortium and have been approved by the review board at the corresponding authors’ institution.

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Huynh-Le, MP., Karunamuni, R., Fan, C.C. et al. Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men. Prostate Cancer Prostatic Dis 24, 845–851 (2021). https://doi.org/10.1038/s41391-021-00341-4

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