Birth order, sibship size, and risk for germ-cell testicular cancer

Background: Several studies have reported an inverse association between birth order and testicular cancer risk, but estimates vary greatly and the biologic mechanism underlying the association is not established. Methods: We have evaluated the effect of birth order, sibship size, and the combined effect of these 2 variables in relation to risk for testicular cancer in a large, nested case-control study. Specifically, we compared 3051 patients with germ-cell testicular cancer (diagnosed between 1958 and 1998 and identified through the Swedish Cancer Registry) with 9007 population control subjects. Using record linkage with the Multi-General ion Register and the Census, we obtained information on number, order, and sex of the subjects' siblings, parental age, and paternal socioeconomic status. Results: Both birth order and sibship size had an inverse and monotonically decreasing association with testicular cancer risk after adjusting for parental age, paternal socioeconomic status, and twin status. The associations were modified by subjects' cohort of birth and were not present among those born after 1959. The odds ratio for having at least 3 siblings, compared with none, was 0.63 (95% confidence interval = 0.53-0.75) among subjects born before 1960. Stratified analyses showed that birth order and number of younger siblings had a similar inverse association with the risk for testicular cancer. Conclusions: Sibship size, and not only birth order, is associated with testicular cancer risk. This suggests a higher prevalence of parental subfertility among patients with testicular cancer.