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

Uldbjerg, Cecilie S. ; Lim, Youn Hee ; Beck, Astrid L. ; Petersen, Jørgen H. ; Sørensen, Karina M. ; Kristensen, David M. ; Rantakokko, Panu ; Coull, Brent A. ; Lindh, Christian LU orcid and Skakkebæk, Niels E. , et al. (2025) In Environment International 203.
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Fetal programming, Maternal serum, Per- and polyfluoroalkyl substances, Pregnancy, Testicular germ cell cancer
in
Environment International
volume
203
article number
109762
publisher
Elsevier
external identifiers
  • scopus:105014757445
  • pmid:40902259
ISSN
0160-4120
DOI
10.1016/j.envint.2025.109762
language
English
LU publication?
yes
id
7a255b9a-7ea5-4043-abd0-c248b6e3852f
date added to LUP
2025-10-16 12:08:54
date last changed
2025-10-30 13:08:26
@article{7a255b9a-7ea5-4043-abd0-c248b6e3852f,
  abstract     = {{<p>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.</p>}},
  author       = {{Uldbjerg, Cecilie S. and Lim, Youn Hee and Beck, Astrid L. and Petersen, Jørgen H. and Sørensen, Karina M. and Kristensen, David M. and Rantakokko, Panu and Coull, Brent A. and Lindh, Christian and Skakkebæk, Niels E. and Hauser, Russ and Bräuner, Elvira V. and Priskorn, Lærke and Juul, Anders}},
  issn         = {{0160-4120}},
  keywords     = {{Fetal programming; Maternal serum; Per- and polyfluoroalkyl substances; Pregnancy; Testicular germ cell cancer}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Environment International}},
  title        = {{Exposure to per- and polyfluoroalkyl substances during fetal development and risk of testicular germ cell cancer in adulthood}},
  url          = {{http://dx.doi.org/10.1016/j.envint.2025.109762}},
  doi          = {{10.1016/j.envint.2025.109762}},
  volume       = {{203}},
  year         = {{2025}},
}