• Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
• National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
• Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, MA, USA.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are highly persistent chemicals that have been detected in the serum of > 98% of the U.S. population. Studies among highly exposed individuals suggest an association with perfluorooctanoic acid (PFOA) exposure and kidney cancer. It remains unclear whether PFOA or other PFAS are renal carcinogens, or if they influence risk of renal cell carcinoma (RCC) at concentrations observed in the general population.

METHODS: We measured pre-diagnostic serum concentrations of PFOA and seven additional PFAS in 324 RCC cases and 324 individually matched controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) relating serum PFAS concentrations and RCC risk. Individual PFAS were modeled continuously (log2-transformed) and categorically, with adjustment for kidney function and additional potential confounders. All statistical tests were two-sided.

RESULTS: We observed a positive association with RCC risk for PFOA (doubling in serum concentration, ORcontinuous = 1.71, 95% CI = 1.23 to 2.37; P = .002), and a greater than two-fold increased risk among those in the highest quartile vs. the lowest (OR = 2.63, 95% CI = 1.33 to 5.20; Ptrend = .007). The association with PFOA was similar after adjustment for other PFAS (ORcontinuous = 1.68, 95% CI = 1.07 to 2.63; P = .02), and remained apparent in analyses restricted to individuals without evidence of diminished kidney function and in cases diagnosed ≥8 years after phlebotomy.

CONCLUSIONS: Our findings add substantially to the weight of evidence that PFOA is a renal carcinogen and may have important public health implications for the many individuals exposed to this ubiquitous and highly persistent chemical.