Maternal Smoking During Pregnancy and Risk of Testicular Germ Cell Tumours in Sons

Background: Testicular cancer, predominantly testicular germ cell tumours, is among the most common cancers in young men. Prenatal factors have been suggested to influence disease aetiology, but evidence regarding maternal smoking during pregnancy is inconsistent. We examined whether maternal smoking during pregnancy was associated with the risk of seminoma and non-seminoma in sons. Methods: We conducted a nationwide Danish cohort study using data from the Danish Medical Birth Register and the Danish Cancer Registry. The study included liveborn Danish males born from 1991 to 2009. Follow-up started from age 15 years until testicular cancer diagnosis, emigration, death, or 31 December 2024, whichever came first. Maternal smoking during pregnancy was obtained prospectively. Cox proportional hazards models with propensity score weights were used to estimate hazard ratios and 95% confidence intervals separately for seminoma and non-seminoma. Results: The final study population comprised 565,358 sons, of whom 126,133 (22.3%) had mothers who smoked during pregnancy, and 439,225 (77.7%) had non-smoking mothers. During follow-up, 641 testicular cancer cases were identified, including 239 seminomas and 395 non-seminomas. Maternal smoking during pregnancy was associated with a higher hazard of seminoma (HR: 1.27, 95% CI: 0.91-1.78) and a lower hazard of non-seminoma (HR: 0.81, 95% CI: 0.61-1.09), although neither estimate reached statistical significance. Conclusions: Maternal smoking during pregnancy was not significantly associated with testicular germ cell tumour risk overall, but the subtype-specific estimates suggested possible heterogeneity, with a tendency toward increased seminoma risk and decreased non-seminoma risk.