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Huynh-Le MP, Karunamuni R, Fan CC, et al. Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men. Prostate Cancer Prostatic Dis. 2021;24(3):845-851doi: 10.1038/s41391-021-00341-4.
Huynh-Le, M. P., Karunamuni, R., Fan, C. C., Thompson, W. K., Muir, K., Lophatananon, A., Tye, K., Wolk, A., Håkansson, N., Mills, I. G., Andreassen, O. A., Dale, A. M., Seibert, T. M. (2021). Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men. Prostate cancer and prostatic diseases, 24(3), 845-851. https://doi.org/10.1038/s41391-021-00341-4
Huynh-Le, Minh-Phuong, et al. "Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men." Prostate cancer and prostatic diseases vol. 24,3 (2021): 845-851. doi: https://doi.org/10.1038/s41391-021-00341-4
Huynh-Le MP, Karunamuni R, Fan CC, Thompson WK, Muir K, Lophatananon A, Tye K, Wolk A, Håkansson N, Mills IG, Andreassen OA, Dale AM, Seibert TM. Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men. Prostate Cancer Prostatic Dis. 2021 Sep;24(3):845-851. doi: 10.1038/s41391-021-00341-4. Epub 2021 Mar 15. PMID: 33723363; PMCID: PMC8387332.
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Prostate Cancer Prostatic Dis. 2021 Sep;24(3):845-851. doi: 10.1038/s41391-021-00341-4. Epub 2021 Mar 15.

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

Prostate cancer and prostatic diseases

Minh-Phuong Huynh-Le, Roshan Karunamuni, Chun Chieh Fan, Wesley K Thompson, Kenneth Muir, Artitaya Lophatananon, Karen Tye, Alicja Wolk, Niclas Håkansson, Ian G Mills, Ole A Andreassen, Anders M Dale, Tyler M Seibert,

Affiliations

  1. Division of Radiation Oncology, George Washington University, Washington, DC, USA.
  2. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
  3. Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
  4. Division of Biostatistics and Halicio?lu Data Science Institute, University of California San Diego, La Jolla, CA, USA.
  5. Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
  6. Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK.
  7. Warwick Medical School, University of Warwick, Coventry, UK.
  8. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  9. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  10. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  11. NORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway.
  12. Department of Radiology, University of California San Diego, La Jolla, CA, USA.
  13. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. [email protected].
  14. Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA. [email protected].
  15. Department of Radiology, University of California San Diego, La Jolla, CA, USA. [email protected].
  16. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. [email protected].

PMID: 33723363 PMCID: PMC8387332 DOI: 10.1038/s41391-021-00341-4

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

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.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

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