Sport, genetic susceptibility, and the risk of benign prostatic hyperplasia: a large prospective cohort study

Benign prostatic hyperplasia (BPH) is a common age-related urological condition influenced by both modifiable lifestyle factors and genetic susceptibility. This large cohort study was performed to examine the association between physical activities and incident BPH, and assess modification by genetic susceptibility using a polygenic risk score (PRS).

We conducted a prospective cohort study of 80,253 men from the UK Biobank who were free of BPH and prostate cancer at baseline. Physical activity was assessed using self-reported total weekly activity time, including walking, moderate, and vigorous activities. Genetic susceptibility was quantified using a BPH-specific PRS. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident BPH. Multiplicative interaction between walking and genetic susceptibility was evaluated by including product terms between walking quartiles and PRS tertiles in Cox proportional hazards models.

Over a median follow-up of 15.01 years, 11,926 incident BPH cases were identified. Higher total weekly physical activity was significantly associated with a lower risk of BPH, with walking showing the strongest protective association. Higher PRS was strongly and independently associated with increased BPH risk. Stratified analyses suggested a modest inverse association between walking and BPH among men with high genetic susceptibility, but the formal multiplicative interaction between walking and PRS did not reach statistical significance.

Physical activity and genetic susceptibility were independently associated with incident BPH. Stratified analyses suggested possible differences across genetic risk groups, but formal interaction testing did not provide robust evidence of effect modification. These observational findings are exploratory and require validation in independent cohorts.