Shared Inherited Genetics of Benign Prostatic Hyperplasia and Prostate Cancer.

Background: The association between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remains controversial, largely due to a detection bias in traditional observational studies.
Objective: To assess the association between BPH and PCa using inherited single nucleotide polymorphisms (SNPs).
Design Setting and Participants: The participants were White men from the population-based UK Biobank (UKB).
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).
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 (χ ²  = 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; χ ² test). Furthermore, significant cross-disease GRS associations were also found; GRS _BPH was significantly associated with PCa risk (odds ratio [OR] = 1.26 [1.18-1.36], p  < 0.001), and GRS _PCa was significantly associated with BPH risk (OR = 1.03 [1.02-1.04], p  < 0.001). Moreover, GRS _BPH 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.
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.
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.
(© 2022 The Authors.)