Exposure to per- and polyfluoroalkyl substances during fetal development and risk of testicular germ cell cancer in adulthood.

BACKGROUND

Testicular germ cell cancer (TGCC) originates during fetal life. Fetal exposure to environmental chemicals may contribute to its development, but epidemiological data are lacking. We investigated per- and polyfluoroalkyl substances (PFAS), which can act as endocrine disruptors during fetal development, and TGCC risk in adulthood.

METHODS

We conducted a nested case-control study of 549 mother-male offspring pairs (103 TGCC cases, 446 matched controls). The source population included over 100,000 pregnant women with biobanked serum samples collected during 1985-1994, a period before PFAS restrictions. Male offspring were followed for up to 38 years, and TGCC cases were identified from the Danish Cancer Registry based on histological confirmation. Eight PFAS were quantified in maternal serum using LC-MS/MS. Associations between individual PFAS and their mixtures with TGCC risk were assessed through Cox regression and quantile g-computation models.

RESULTS

Associations between individual PFAS and TGCC risk were modest and not statistically significant. Hazard ratios (HRs) for perfluoroalkyl sulfonic acids (PFOS, PFHxS, PFHpS) suggested higher TGCC risks per quartile increase in concentrations, but lower risks for perfluoroalkyl carboxylic acids (PFOA, PFNA, PFDA, PFHpA, PFUnDA). Mixture analyses supported this pattern, with higher TGCC risk for the joint effect of sulfonic acids (HR 1.13, 95 % CI: 0.89; 1.44). Stratified analyses by histological subtype showed higher risk for seminomas than for nonseminomas across all PFAS.

CONCLUSIONS

We found limited evidence of an association between fetal PFAS exposure and TGCC risk. Indications of a potential adverse effect of perfluoroalkyl sulfonic acids, particularly for seminomas, merit further research.