PFAS Exposure Linked to Higher Nonmelanoma Skin Cancer Risk, Especially in Older Adults

A potential link between high perfluorodecanoic acid (PFDA) exposure and nonmelanoma skin cancer (NMSC), particularly among older adults, underscores the need for ongoing per- and polyfluoroalkyl substances (PFAS) monitoring, according to a study recently published in Biomolecules & Biomedicine.¹

Rising PFAS Exposure Prompts Concern Over Health Risks

The researchers described PFAS as a class of synthetic chemicals characterized by a carbon chain bonded to multiple fluorine atoms, often referred to as perfluorinated or polyfluorinated backbones. First introduced in the 1940s, PFAS have since been widely used in consumer products and industrial applications due to their resistance to heat, water, and oil.

These compounds are commonly found in water- and stain-resistant textiles, carpets, household cleaners, paints, and fire-fighting foams. As a result, PFAS contamination has become increasingly widespread, particularly in the US, where human exposure occurs through food, air, soil, indoor dust, and drinking water. Between 2013 and 2015, PFAS levels exceeding reporting thresholds were detected in 194 of 4864 tested public water systems, affecting approximately 6 million people.²

Concerns about the health effects of PFAS exposure continue to grow.¹ Prior research has linked PFAS exposure to adverse health outcomes, including altered immune function, insulin resistance, and reproductive complications. Experimental evidence also suggests PFAS may induce oxidative stress and DNA damage in skin cells, suggesting a potential association between exposure and skin cancer.

To further investigate this relationship, investigators conducted a study examining the association between PFAS exposure and NMSC, focusing on 3 understudied compounds: PFDA, perfluoroundecanoic acid (PFUnDA), and 2-(N-methyl-PFOSA) acetate. Subgroup analyses were also performed to assess whether associations differed by age and sex.

PFAS Exposure and NMSC Associations

This cross-sectional study used data from 8 cycles of the National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. PFAS exposure was measured using serum samples and analyzed as tertiles, detectable vs undetectable levels, and log-transformed continuous variables. Meanwhile, skin cancer outcomes were based on self-reported physician diagnosis.

The investigators used multivariable logistic regression models, adjusting for age, sex, race/ethnicity, body mass index, smoking status, and NHANES cycle. They also conducted exploratory age- and sex-stratified analyses using Firth penalized logistic regression, using multiple imputation to address potential selection bias due to missing covariates.

The analysis included 44,790 adults, but the final analytic sample comprised 5934 for NMSC. Within the NMSC cohort, only 104 individuals received a diagnosis, with prevalence significantly higher among men than women (58.7% vs 41.3%; P = .044).

Most participants had a body mass index (BMI) of 30 or greater, with similar distributions between those with and without NMSC. Serum levels of most PFAS compounds were also comparable across groups, except for 2-(N-methyl-PFOSA) acetate, which was modestly higher among individuals with NMSC (P < .001).

In minimally adjusted multivariable models, participants in the second tertile of PFDA exposure had significantly higher odds of NMSC compared with those in the lowest tertile (adjusted OR [aOR], 1.73; 95% uncertainty interval [UI], 1.01–2.89; P = .048). However, this association was not observed in the highest tertile. Similarly, PFUnDA and 2-(N-methyl-PFOSA) acetate were not significantly associated with NMSC across tertiles or when modeled as continuous or binary exposures.

Age-stratified analyses showed a stronger association between PFDA exposure and NMSC among adults aged 60 and older. In particular, individuals in the second tertile had more than twice the odds of NMSC than those in the lowest tertile (aOR, 2.29; 95% UI, 1.29–4.05; P = .004). However, no clear association was observed in younger adults.

Additionally, sex-stratified analyses showed generally higher, but not statistically significant, odds of NMSC with increasing PFDA exposure in both men and women, with no evidence of interaction by sex.

Lastly, multiple imputation attenuated the observed association between PFDA and NMSC in the second tertile (aOR, 1.34; 95% UI, 0.92–1.93), suggesting that complete-case analyses may have overestimated this relationship. Still, results for other PFAS exposures remained consistent.

Next Steps in Understanding PFAS Risks

The researchers acknowledged several limitations, including the cross-sectional design, which prevents them from establishing a causal link between PFAS and NMSC. Another is the reliance on self-reported cancer diagnoses, which may introduce recall bias or misclassification. Nonetheless, they emphasized that their findings lay the groundwork for further research to clarify the biological processes linking PFAS exposure to NMSC.

“Our findings underscore the necessity for ongoing monitoring and the implementation of control strategies in settings at risk for elevated PFAS exposures,” the authors concluded.

References

1. Siddiqui S, Siddiqui H, Nagi K, Malki MI. Higher serum PFDA is associated with increased non-melanoma skin cancer odds in NHANES 2003-2018. Biomol Biomed. Published online April 3, 2026. doi:10.17305/bb.2026.13621
2. Hu XC, Andrews DQ, Lindstrom AB, et al. Detection of poly- and perfluoroalkyl substances (PFASs) in U.S. drinking water linked to industrial sites, military fire training areas, and wastewater treatment plants. Environ Sci Technol Lett. 2016;3(10):344-350. doi:10.1021/acs.estlett.6b00260