| Title: | Shared Inherited Genetics of Benign Prostatic Hyperplasia and Prostate Cancer |
| Journal: | European Urology Open Science |
| Published: | 1 Aug 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36353071/ |
| DOI: | https://doi.org/10.1016/j.euros.2022.07.004 |
| Citations: | 9 (9 in last 2 years) as of 8 Aug 2024 |
Publication 12285
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Background: The association between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remains controversial, largely due to a detection bias in traditional observational studies.</p>
Objective: To assess the association between BPH and PCa using inherited single nucleotide polymorphisms (SNPs).</p>
Design setting and participants: The participants were White men from the population-based UK Biobank (UKB).</p>
Outcome measurements and statistical analysis: The association between BPH and PCa was tested for (1) phenotypic correlation using chi-square, (2) genetic correlation (r g) based on genome-wide SNPs using linkage disequilibrium score regression, and (3) cross-disease genetic associations based on known risk-associated SNPs (15 for BPH and 239 for PCa), individually and cumulatively using genetic risk score (GRS).</p>
Results and limitations: Among 214 717 White men in the UKB, 24 623 (11%) and 14 311 (6.7%) had a diagnosis of BPH and PCa, respectively. Diagnoses of these two diseases were significantly correlated (χ2 = 1862.80, p < 0.001). A significant genetic correlation was found (r g = 0.16; 95% confidence interval 0.03-0.28, p = 0.01). In addition, significant cross-disease genetic associations for established risk-associated SNPs were also found. Among the 250 established genome-wide association study-significant SNPs of PCa or BPH, 49 were significantly associated with the risk of the other disease at p < 0.05, significantly more than expected by chance (N = 12, p < 0.001; χ2 test). Furthermore, significant cross-disease GRS associations were also found; GRSBPH was significantly associated with PCa risk (odds ratio [OR] = 1.26 [1.18-1.36], p < 0.001), and GRSPCa was significantly associated with BPH risk (OR = 1.03 [1.02-1.04], p < 0.001). Moreover, GRSBPH was significantly and inversely associated with lethal PCa risk in a PCa case-case analysis (OR = 0.58 [0.41-0.81], p = 0.002). Only White men were studied.</p>
Conclusions: BPH and PCa share common inherited genetics, which suggests that the phenotypic association of these two diseases in observational studies is not entirely caused by the detection bias.</p>
Patient summary: For the first time, we found that benign prostatic hyperplasia and prostate cancer are genetically related. This finding may have implications in disease etiology and risk stratification.</p>
13 Authors
- Alexander Glaser
- Zhuqing Shi
- Jun Wei
- Nadia A. Lanman
- Skylar Ladson-Gary
- Renee E. Vickman
- Omar E. Franco
- Susan E. Crawford
- S. Lilly Zheng
- Simon W. Hayward
- William B. Isaacs
- Brian T. Helfand
- 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 |
Enabling scientific discoveries that improve human health