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.