Paternal age and risk of testicular germ cell tumors: a cohort study of 1,000,000 men.

Testicular germ cell tumors (TGCT) are the most frequent cancer among young men, with increasing incidence worldwide. Advanced paternal age has been linked to adverse health outcomes in offspring, but reports on the association of paternal age with TGCT are few and inconsistent. We aimed to examine the relationship of paternal age (PAB) at birth with the risk of TGCT and by histologic type: seminoma and non-seminoma. A population-based cohort of 1,056,058 males, examined at ages 16-19 between the years 1980-2011, was linked to the Israel National Cancer Registry to obtain incident TGCT through 2012. We applied multivariable Cox regression. During 16.5 million person-years of follow-up, 1247 incident cases (604 seminomas and 643 non-seminomas) were detected. Increasing PAB was linearly associated with lower risk of TGCT (HRper year  = 0.983, 95% CI: 0.974-0.993, p = 0.001), after adjustment for year of birth, years of education, height, cryptorchidism history and origin, and also with additional adjustment for maternal age at birth (MAB) (HRper year  = 0.980: 0.965-0.995, p = 0.008). The association was stronger for seminoma (HRper year  = 0.968: 0.946-0.989, p = 0.004) and persisted in a subset adjusted for sibship size (HRper year  = 0.950: 0.917-0.983, p = 0.003). In the fully adjusted model, young PAB (15-24 vs. ≥30) was a risk factor for seminoma (HR = 1.41: 1.07-1.85, p = 0.014). In models adjusted for PAB, MAB was not associated with risk of TGCT. In conclusion, our findings suggest that young paternal age is a risk factor of TGCT, especially seminoma. The findings warrant further investigation into the possible impact of young paternal age on their offsprings' testes.