Serum concentrations of per- and polyfluoroalkyl substances and testicular cancer risk: A nested case-control study within the Military Aviators Cancer Study

Principal Investigator

Name
Mark Purdue

Degrees
PhD

Institution
National Cancer Institute

Position Title
Senior Investigator

Email
purduem@mail.nih.gov

About this CDAS Project

Study
MACS (Learn more about this study)

Project ID
2026-0144

Initial CDAS Request Approval
Nov 4, 2026

Title
Serum concentrations of per- and polyfluoroalkyl substances and testicular cancer risk: A nested case-control study within the Military Aviators Cancer Study

Summary
Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic fluorinated chemicals that were used for many decades in the manufacture of some firefighting foams, non-stick cookware coating and other products. These chemicals have emerged as important environmental pollutants because of their resistance to degradation and concerns that they may increase the risk of some cancers. In 2023, the International Agency for Research on Cancer (IARC) classified perfluorooctanoic acid (PFOA) as a human carcinogen (Group 1) based on sufficient evidence in experimental animals, strong mechanistic evidence in exposed humans and limited epidemiologic evidence of associations with cancers of the kidney and testis. Perfluorooctanesulfonic acid (PFOS) was classified by IARC as a possible human carcinogen (Group 2B) based on strong mechanistic evidence and inconclusive epidemiologic evidence.

Military sites with a history of using PFAS-containing aqueous film-forming foams for firefighting are a major source of PFAS environmental release into public water supplies. In a 2016-2017 systematic water testing of military facilities, the Department of War identified 401 installations with a known or suspected release of PFOS/PFOA, including 90 with tested groundwater PFOS/PFOA concentrations exceeding the 2016 EPA LHA of 70 parts per trillion (ppt), and 36 with tested drinking water PFOS/PFOA concentrations exceeding this threshold.

Until recently, no studies investigating PFAS associations with cancer among military servicemembers had been conducted. In a nested case-control study among Air Force servicemen using banked samples from the DoD Serum Repository (DODSR), we observed elevated pre-diagnostic serum PFOS concentrations to be associated with an increased risk of testicular cancer diagnosed during active-duty service. We also observed suggestive evidence of positive associations with testicular cancer for military pilots and aircraft maintenance crew. However, a limitation of that study was the inability to investigate associations with testicular cancers diagnosed after separation from active duty; given the generally long latency period for most types of cancer, it is possible that any cancer risks from PFAS exposures incurred during military service are stronger in the follow-up time period after separation from active duty.

The Military Aviators Cancer Study (MACS) represents a valuable opportunity to address this research gap and extend our investigations of DoDSR serum PFAS concentrations and testicular cancer to cancers diagnosed after active-duty service.

Aims

The primary aims of our proposed project are:

1. To investigate the associations between pre-diagnostic serum concentrations of PFOS, PFOA and other PFAS chemicals and risk of testicular cancer among MACS participants; and

2. To characterize other exogenous exposures and investigate metabolic perturbations and related pathways through which PFAS exposures may influence risk of testicular cancer.

We hypothesize that the risk of testicular cancer increases with increasing serum concentrations of PFOS and other PFAS among military service members with potential exposures from contaminated water supplies and other sources, and that metabolic perturbations reflect biological processes underlying associations between PFAS exposures and testicular cancer risk.

As secondary research aims in this study, we will also perform the following:

1. Explore differences by population characteristics (e.g., age, race and ethnicity) in the relationship between serum PFAS concentrations and testicular cancer risk;

2. Examine whether the associations with serum PFAS concentrations differ by histologic subtype of testicular cancer (seminomas vs. nonseminomas); and

3. Characterize potential determinants of serum PFAS concentrations such as military occupational specialty codes, history of being stationed at installations with high , and other factors.

Collaborators

Mark Purdue (National Cancer Institute)
Jonathan Hofmann (National Cancer Institute)
Ruth Pfeiffer (National Cancer Institute)
Katherine McGlynn (National Cancer Institute)
Jongeun Rhee (Uniformed Services University of the Health Sciences)