Exposure to per- and polyfluoroalkyl substances and the odds of renal cell carcinoma: a case-control study

An association between per- and polyfluoroalkyl substances (PFAS) exposure and renal cell carcinoma (RCC) has been suggested, but epidemiological evidence remains limited. We conducted a case-control study of RCC in Okinawa, a potentially highly PFAS-exposed population due to firefighting foam from military airbases. The study included patients with pathologically confirmed primary RCC and control participants. Serum PFAS concentrations were categorized into tertiles. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for RCC. Models were fitted with and without adjustment for estimated glomerular filtration rate to evaluate potential overadjustment. Participants in the highest PFOS tertile had significantly higher odds of RCC than those in the lowest tertile, whereas PFOA and PFHxS showed inverse associations. This association remained significant in models fitted with eGFR (OR 11.3, 95% CI 3.52-41.6), and without eGFR (OR 10.83, 95% CI 3.46-38.57). Mixture analyses were inconsistent across methods, and quantile g-computation showed no overall mixture effect (OR 0.96, 95% CI 0.77-1.19). Elevated serum PFOS concentrations were associated with higher odds of RCC in this highly exposed population. These findings provide epidemiological evidence supporting a potential link between PFOS exposure and RCC and underscore the need for prospective studies to clarify causality.