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 ( ) 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 = 1862.80,  < 0.001). A significant genetic correlation was found (  = 0.16; 95% confidence interval 0.03-0.28,  = 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  < 0.05, significantly more than expected by chance ( = 12,  < 0.001; χ test). Furthermore, significant cross-disease GRS associations were also found; GRS was significantly associated with PCa risk (odds ratio [OR] = 1.26 [1.18-1.36],  < 0.001), and GRS was significantly associated with BPH risk (OR = 1.03 [1.02-1.04],  < 0.001). Moreover, GRS was significantly and inversely associated with lethal PCa risk in a PCa case-case analysis (OR = 0.58 [0.41-0.81],  = 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.