Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort

Recent studies have suggested the involvement of loci on the Y chromosome in prostate cancer. We studied the relative risk (RR) of prostate cancer in relation to sex ratio of offspring in a cohort of 38,934 Israeli men who were followed from the birth of their offspring (in 1964 through 1976) until 2005. Cox models were used to adjust for changes in incidence over time, age, the man's year of birth, and social and ethnic variables. A total of 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had an increased risk of prostate cancer (adjusted RR = 1.40, 95% confidence interval [CI] = 1.20 to 1.64, P<.0001). In men with one, two, or three or more offspring, the relative risks associated with absence of sons were 1.25 (95% CI = 1.00 to 1.56), 1.41 (95% CI = 1.04 to 1.91), and 1.60 (95% CI = 1.05 to 2.43), respectively. Men with no daughters showed no statistically significantly altered risk, compared with men who had offspring of both sexes. The relative risk of prostate cancer decreased as the number of sons increased (P(trend)<.0001) but did not change with the number of daughters. These findings suggest that a Y chromosome locus may be involved in prostate cancer risk in this population.