Late fetal death in offspring and subsequent incidence of prostate cancer in fathers: The Jerusalem perinatal study cohort

BACKGROUND. Little is known of the causes of prostate cancer and few previous studies have investigated men's reproductive histories in relation to this disease. We sought to determine whether risk of prostate cancer was altered in men who had fathered stillborn offspring. METHODS. We studied the incidence of prostate cancer (N = 252) in a cohort of 15,268 fathers followed for 28-41 years from the birth of a live offspring, whose wives participated in one of two separa te surveys of outcomes of previous births. Proportional hazards models were used to estimate relative risks (RR) associated with previous stillbirths, controlling for changes in incidence over time, social and occupational factors. RESULTS. The 543 men with one or more stillborn offspring experienced an increased risk of prostate cancer (adjusted RR = 1.87,95% confidence interval = 1.17-3.00, P = 0.0095), compared to men without stillbirths. With one reported stillbirth, the RR was 1.68 (0.99-2.84); with two or more, the RR was 3.29 (1.22-8.88). Results were consistent in men whose wives were interviewed in 1965-1968 and 1974-1976. In 100 fathers with no male offspring and at least one stillbirth the RR was 4.04 (1.87-8.71, P = 0.0004). CONCLUSIONS. These findings should be considered hypothesis-generating and require confirmation in other studies. They suggest that stillbirth and prostate cancer may have shared environmental causes; alternatively, genetic susceptibility to prostate cancer might increase the risk of a stillbirth in offspring.