Gestational age at birth and risk of testicular cancer

Most testicular germ cell tumors originate from carcinoma in situ cells in fetal life, possibly related to sex hormone imbalances in early pregnancy. Previous studies of association between gestational age at birth and testicular cancer have yielded discrepant results and have not examined extreme preterm birth. Our objective was to determine whether low gestational age at birth is independently associated with testicular cancer in later life. We conducted a national cohort study of 354,860 men born in Sweden in 1973-1979, including 19,214 born preterm (gestational age < 37 weeks) of whom 1,279 were born extremely preterm (22-29 weeks), followed for testicular cancer incidence through 2008. A total of 767 testicular cancers (296 seminomas and 471 nonseminomatous germ cell tumors) were identified in 11.2 million person-years of follow-up. Extreme preterm birth was associated with an increased risk of testicular cancer (hazard ratio = 3.95; 95% confidence interval = 1.67-9.34) after adjusting for other perinatal factors, family history of testicular cancer and cryptorchidism. Only five cases (three seminomas and two nonseminomas) occurred among men born extremely preterm, limiting the precision of risk estimates. No association was found between later preterm birth, post-term birth or low or high fetal growth and testicular cancer. These findings suggest that extreme but not later preterm birth may be independently associated with testicular cancer in later life. They are based on a small number of cases and will need confirmation in other large cohorts. Elucidation of the key prenatal etiologic factors may potentially lead to preventive interventions in early life.