Serum concentrations of per- and polyfluoroalkyl substances and kidney cancer risk: A nested case-control study among military aviators and aviation support personnel
Principal Investigator
Name
Jonathan Hofmann
Degrees
PhD, MPH
Institution
National Cancer Institute
Position Title
Senior Investigator
Email
hofmannjn@mail.nih.gov
About this CDAS Project
Study
MACS
(Learn more about this study)
Project ID
2026-0131
Initial CDAS Request Approval
Aug 17, 2026
Title
Serum concentrations of per- and polyfluoroalkyl substances and kidney cancer risk: A nested case-control study among military aviators and aviation support personnel
Summary
PFAS are synthetic chemicals that have been used as surfactants in aqueous film forming foams (AFFFs) and a variety of other industrial and commercial applications. Many PFAS are highly persistent in the environment and can bioaccumulate in humans, with serum elimination half-lives ranging from approximately 2-8 years. The Department of War (DoW) has used AFFFs containing PFOA, PFOS, and other PFAS since the 1970’s for firefighting operations at airfield crash sites and in fire training areas and maintenance hangars at many installations, and 401 active or closed military bases with a known or suspected release of PFOA/PFOS have been identified. The majority of these military installations (203 of 401) were Air Force bases.
In 2023, the International Agency for Research on Cancer (IARC) classified PFOA, the most well-studied PFAS, as a human carcinogen based partly on limited epidemiologic evidence of associations with kidney and testicular cancers. PFOS was classified as a possible human carcinogen with inadequate epidemiologic evidence for all cancer sites. Higher kidney cancer incidence and mortality were observed among individuals highly exposed to PFOA due to contamination from a fluoropolymer production plant in the mid-Ohio Valley. In prospective studies of population with background levels of PFAS exposure, we observed associations between higher serum PFOA concentrations and increased kidney cancer risk in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and among non-Hispanic White participants in the Multiethnic Cohort (MEC).
Following up on these findings, we propose to investigate the relationship between pre-diagnostic serum PFAS concentrations and risk of kidney cancer among aviators and aviation support personnel. The Military Aviators Cancer Study (MACS) is a Congressionally mandated cohort of U.S. military aircrew (N=156,050) and groundcrew (N=737,891). Prior analyses in Phase 1 of the MACS revealed an increased incidence of kidney cancer among aviation support personnel relative to the general U.S. population (SIR=1.12, 95%CI 1.06-1.18). However, the contributions of specific exposures such as PFAS to this excess remain unclear. Our proposed study will provide important evidence to clarify the role of PFOA and other PFAS in the development of kidney cancer. It will be, to our knowledge, the first investigation of the relationship between PFAS exposure and risk of kidney cancer among military aviators and the largest investigation of PFAS and kidney cancer risk to date.
Beyond exposures to PFOA and other PFAS, military aircrew and ground crew are likely exposed to a range of other occupational and environmental chemicals that may influence the risk of developing kidney cancer, such as some polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene), industrial solvents, and certain pesticides. The relationships with kidney cancer for other chemicals associated with military flight operations (e.g., jet propellant fuels, aircraft engine exhaust) are less well understood. Untargeted metabolomics approaches can be informative for characterizing internal doses of these and other exogenous chemical exposures among military aircrew and ground crew, and have the potential to provide new insights into the role of these exposures in the development of kidney cancer in this population.
Aims
The primary aims of our proposed project are:
1. To investigate the associations between pre-diagnostic serum concentrations of PFOA and other PFAS and risk of kidney cancer among military aviators and aviation support personnel; and
2. To characterize other exogenous exposures and endogenous metabolic perturbations that are associated with risk of kidney cancer.
Our investigation will leverage the collection of sera from military personnel during military service. We hypothesize that the risk of kidney cancer increases with increasing serum concentrations of PFOA and other PFAS among military service members with potential exposures from contaminated water supplies and other sources, and that metabolites reflecting other exogenous chemical exposures and endogenous metabolic perturbations will be associated with kidney cancer risk.
As secondary research aims in this study, we will also perform the following:
1. Explore differences by study group (aircrew, aviation support personnel) and other population characteristics (e.g., age, sex, race and ethnicity) in the relationship between serum PFAS concentrations and risk of kidney cancer;
2. Determine whether the associations between serum PFAS concentrations and kidney cancer risk are modified by kidney function [estimated glomerular filtration rate (eGFR)] or other factors (e.g., hypertension);
3. Examine whether the associations with serum PFAS concentrations differ by stage or histologic subtype of kidney cancer (clear cell vs. non-clear cell histology);
4. Explore metabolic perturbations and related pathways through which PFAS and other chemical exposures may influence risk of kidney cancer; and
5. Characterize potential determinants of serum PFAS concentrations such as job duties, service history, and other factors.
This proposed study directly addresses the Phase 2 objective of investigating cancer risk in relation to military exposures (“toxic and hazardous exposures”) among aviators and aviation support personnel and identifying occupational and environmental risk factors that may contribute to the excess of kidney cancer that has been observed among ground crew in this study population relative to the general U.S. population in Phase 1 of the study.
Collaborators
Jonathan Hofmann (National Cancer Institute)
Jongeun Rhee (Henry M. Jackson Foundation for the Advancement of Military Medicine)
Mark Purdue (National Cancer Institute)
Gregory Chestnut (Walter Reed National Military Medical Center)
Vicky Chang (National Cancer Institute)
Jennifer Rusiecki (Uniformed Services University)