Shared Inherited Genetics of Benign Prostatic Hyperplasia and Prostate Cancer

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BackgroundThe association between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remains controversial, largely due to a detection bias in traditional observational studies. ObjectiveTo assess the association between BPH and PCa using inherited single nucleotide polymorphisms (SNPs). Design, setting, and participantsThe participants were White men from the population-based UK Biobank (UKB). Outcome measurements and statistical analysisThe association between BPH and PCa was tested for (1) phenotypic correlation using chi-square, (2) genetic correlation (rg) 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 limitationsAmong 214717 White men in the UKB, 24623 (11%) and 14311 (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 (rg = 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. ConclusionsBPH 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 summaryFor 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.