| Title: | Prostate Cancer, Genetic Susceptibility, and Risk of Chronic Non-Urological Complications |
| Journal: | The Prostate |
| Published: | 29 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42053416/ |
| DOI: | https://doi.org/10.1002/pros.70190 |
Publication 17802
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Abstract
BACKGROUND: Chronic nonurological complications are common among prostate cancer (PCa) survivors; however, their spectrum, magnitude, and genetic contribution remain poorly characterized.</p>
METHODS: We evaluated 15 commonly reported nonurological complications and tested their associations with exposure to PCa and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N = 219,133). Analyses were conducted using cause-specific Cox proportional-hazards models within a full-cohort framework with time-updated PCa status, delayed entry at study recruitment, and age as the underlying time scale.</p>
RESULTS: After recruitment, incident PCa was diagnosed in 13,780 men, of which 1,656 (12.02%) had metastatic PCa (mPCa). Risks for seven complications were higher among men with PCa, adjusting for genetic background (all p < 0.05), including osteoporosis, venous thromboembolism, depression, and four primary cancers (bladder, kidney, colorectal, and pancreatic). Risks were consistently stronger among men exposed to mPCa than non-mPCa; for example, the hazard ratio (HR) (95% confidence interval) for osteoporosis was 1.88 (1.63-2.18) for any PCa, 4.67 (3.11-7.01) for mPCa, and 1.75 (1.50-2.04) for non-mPCa. Elevated risks for three additional complications (coronary artery disease, type 2 diabetes and chronic obstructive pulmonary disease) were observed only among men with mPCa. The risks for these ten complications were further increased among men with higher disease-specific PRS; for example, the HR for osteoperosis in mPCa patients in the top PRS quartile was 13.57 (8.24-22.34) compared with men without PCa (p < 0.001).</p>
CONCLUSION: PCa diagnosis and inherited genetic susceptibility jointly contribute to increased risks of multiple chronic non-urological complications among survivors.</p>
15 Authors
- Brian T. Helfand
- Zhuqing Shi
- Ashley J. Mulford
- Huy Tran
- Jun Wei
- Annabelle Ashworth
- S. Lilly Zheng
- Alan R. Sanders
- Nathan Graham
- Joshua Cabral
- Jim Lu
- Jennifer L. Beebe-Dimmer
- Kathleen A. Cooney
- David Duggan
- Jianfeng Xu
1 Application
| Application ID | Title |
|---|---|
| 50295 | Validity and performance of inherited risk assessment for common diseases using polygenic risk score, family history, and high-penetrance genes |
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