Serum Concentrations of Per- and Polyfluoroalkyl Substances and Risk of Renal Cell Carcinoma

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are highly persistent chemicals that have been detected in the serum of over 98% of the US 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 prediagnostic serum concentrations of PFOA and 7 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 2-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 twofold 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 or more 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.

Figure 1.

Odds ratios (ORs) and 95% confidence intervals (CIs) evaluating serum perfluorooctanoic acid concentrations and risk of renal cell carcinoma in stratified and sensitivity analyses in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. P values represent Wald tests of heterogeneity across strata. BMI = body mass index; ccRCC = clear cell renal cell carcinoma; eGFR = estimated glomerular filtration rate. ^aSelf-reported at study enrollment. ^bBMI-specific analyses exclude individuals with BMI that is missing or less than 18.5 kg/m². ^cAt blood draw. ^dTime from blood draw to diagnosis for cases. ^eInternational Classification of Diseases for Oncology, Second Edition morphology code = 8310. ^fContinuous odds ratios (95% confidence intervals) for RCC risk in relation to a 1-unit increase in serum PFAS concentrations on the log₂ scale, or an approximate doubling in analyte levels, were estimated using unconditional multivariable logistic regression models adjusted for age at enrollment (55-59 years, 60-64 years, 65-69 years, ≥70 years), sex (male, female), race and ethnicity (white non-Hispanic, Black non-Hispanic, or other), eGFR (continuous), BMI (<18.5 kg/m², 18.5 to <25 kg/m², 25 to <30 kg/m², ≥30 kg/m², missing), history of hypertension (no or missing, yes), smoking status (never, former, current), previous freeze-thaw cycle, calendar year of blood draw (1993-1995, 1996-1997, 1998-2002), study year of blood draw (enrollment, other), and study center ([1] Minnesota or Marshfield; [2] Colorado, Hawaii, Washington University, University of Utah, or University of Alabama; [3] Georgetown, Henry Ford, or University of Pittsburgh).