Abstract
BACKGROUND: Fatherhood status has been hypothesized to affect prostate cancer risk but the current evidence is limited and contradictory. METHODS: We prospectively evaluated the relationship between offspring number and the risk of prostate cancer in 161,823 men enrolled in the National Institues of Health - American Association of Retired Persons Diet and Health Study. Participants were aged 50-71 years without a cancer diagnosis at baseline in 1995. Analysing 8134 cases of prostate cancer, Cox regression was used to estimate the association between offspring number and prostate cancer incidence while accounting for socio-demographic and lifestyle characteristics. RESULTS: When examining the entire cohort, there was no relationship between fatherhood and incident prostate cancer [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.86-1.02]. However, after stratifying for prostate cancer screening, prostate-specific antigen (PSA) unscreened childless men had a lower risk of prostate cancer (HR 0.73, 95% CI 0.58-0.91) compared with fathers due to the interaction between PSA screening and fatherhood (P for interaction < 0.01). A trend for the lower risk of prostate cancer among unscreened fathers compared with childless men was seen for low-grade prostate cancer (HR 0.78, 95% CI 0.61-1.01), high-grade prostate cancer (HR 0.62, 95% CI 0.37-1.04) and even fatal prostate cancer (HR 0.28, 95% CI 0.07-1.12). The number of children fathered was not related to prostate cancer (P(trend) = 0.17). In addition, men's inability to sire female offspring showed a weak positive association with prostate cancer in the PSA unscreened study subjects. CONCLUSIONS: Our findings suggest fatherhood status and offspring gender is associated with a man's prostate cancer risk.