Congenital malformations and testicular germ cell tumors

Cryptorchidism is one of the few known risk factors for testicular germ cell tumors (TGCT). It has been postulated that other congenital malformations, in particular hypospadias, are also associated with increased risk; however, associations with birth defects have not been extensively studied. Using Swedish population‐based registries we evaluated the relationship between birth defects and risk of TGCT. TGCT cases (n = 6,593) diagnosed between 15 and 65 years of age were identified from the Swedish Cancer Registry between 1964 and 2008. Five controls per case were randomly selected from the population register and matched on birth year and birth county. Congenital malformations were identified via linkage with the Hospital Discharge Register. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each group of malformations and TGCT were estimated using conditional logistic regression. In addition to the expected association between cryptorchidism and TGCT risk [OR (95% CI): 3.18 (2.50–4.04)], hypospadias [2.41 (1.27–4.57)], inguinal hernia [1.37 (1.11–1.68)] and other genital malformations [2.19 (1.17–4.10)] were associated with an increased risk of TGCT. Mutual adjustment for cryptorchidism, hypospadias, inguinal hernia and other genital malformations did not appreciably change the associations (ORs: 3.16, 2.25, 1.30 and 1.90, respectively). The other (nongenital) malformations evaluated were not associated with TGCT. These data suggest that developmental urogenital abnormalities, specifically cryptorchidism, hypospadias and inguinal hernia, are associated with an increased risk of TGCT, further supporting the hypothesis that prenatal exposure(s) related to proper genital development are related to this tumor. What's new? While cryptorchidism is a known risk factor for testicular germ cell tumors (TGCT), few studies have evaluated the association between other birth defects and risk of TGCT. Using large, population‐based registries in Sweden, the authors evaluated this important question and demonstrate that hypospadias, inguinal hernia, and other genital malformations are associated with an increased risk of TGCT. The findings highlight the importance of prenatal exposures related to proper genital development in the etiology of TGCT.