Dataset Information

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.

SUBMITTER: Shearer JJ

PROVIDER: S-EPMC8096365 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundPer- and polyfluoroalkyl substances (PFAS) exert immunosuppressive effects in experimental animals. Few epidemiologic studies investigated PFAS exposure and immune-related clinical outcomes such as common cold, especially during childhood when the immune system is developing.MethodsThis study used data from the National Health and Nutrition Examination Survey and included 517 children 3-11 years (2013-2014 cycle) and 2732 adolescents 12-19 years (2003-2016 cycles). Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) were quantified. Common cold was self-reported by the participant or parent as having a head cold or chest cold in the last month. Multivariable logistic regression models were applied to examine the covariate-adjusted odds ratios (ORs) between individual PFAS concentrations and common cold incidence in the past month. The joint effect of PFAS mixtures was evaluated using Probit Bayesian Kernel Machine Regression (BKMR).ResultsA doubling of serum PFHxS concentration was associated with a 31% higher odds (OR = 1.31, 95% CI: 1.06, 1.62) of common cold among children. Serum PFNA (OR = 1.36, 95% CI: 0.93, 1.98) and PFOA (OR = 1.32, 95% CI: 0.67, 2.62) concentrations were also related to common cold among children, as were serum PFOS concentrations among adolescents (OR = 1.13, 95% CI: 0.96, 1.32). ORs were higher in male than female children and adolescents. BKMR showed a clear increasing trend of common cold estimates across quantiles of the total PFAS mixture concentration among children, while no obvious pattern emerged in adolescents.DiscussionAmong children in the United States, serum concentrations of PFAS mixtures, especially PFHxS and PFNA, were associated with higher odds of common cold. Among adolescents, PFOS was associated with increased common cold in the last month. This study contributes to the existing evidence supporting the immunotoxicity of PFAS in childhood and adolescence.

Project description:BackgroundResidents of Anniston Alabama were highly exposed to polychlorinated biphenyls (PCBs) due to longstanding manufacturing in the area. The Anniston Community Health Surveys (ACHS I-2005-2007 and II, 2014) have linked these exposures with a variety of deletereous health outcomes. In addition to PCBs, these individuals were likely simultaneously exposed to other persistent organic pollutants including per and polyfluoroalkyl substances (PFAS), which are an emerging class of ubiquitous industrial chemicals that are measurable in the blood of most individuals and have themselves been linked increased risk of some non communicable diseases.MethodsTo characterize PFAS exposures in ACHS I and ACHS II, we measured eight environmentally significant PFAS in serum by UPLC coupled electrospray ionization tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), Perfluorooctanoic acid (PFOA), Perfluorononanoate (PFNA), Perfluorohexane sulfonate (PFHxS), Perfluoroheptanoic acid (PFHpA), Perfluorobutanesulfonic acid (PFBS), Hexafluoropropylene oxide dimer acid (HFPO-DA), and 4:2 Fluorotelomer sulfonic acid (4.2 FTS) were extracted from matched serum samples of individuals who participated in the original ACHS I (2005-2007; n = 297) and the follow up ACHS II (2014; n = 336). Data were collected in negative multiple reaction monitoring (MRM) mode with monitoring of quantitation and qualifier ions for all target PFAS analytes, surrogates and internal standards. VARCLUS procedure was used to create hierarchical clusters between PFAS and other legacy persistent organic pollutants which may share similar exposure routes.ResultsOverall, circulating PFAS levels decreased approximately 50% from ACHS I (2005-2007) to ACHS II (2014), but these changes varied by compound. Mean levels of PFOS were >3 times higher in ACHS I subjects than in conpemporaneous NHANES subjects (2005-2006; ACHS I mean: 71.1 ng/ml; NHANES mean: 20.2 ng/mL), and this relationship persisted in ACHS II subjects (2014: ACHS II mean: 34.7 ng/ml; NHANES mean: 5.92 ng/mL). PFNA was also higher in both ACHS I and ACHS II subjects in comparision to NHANES whereas levels of PFOA and PFHxS were lower than in NHANES. Finally, cluster analysis revealed that in ACHS II, most PFAS tracked with polybrominated diphenyl ethers, except PFNA and PFHpA which clustered with industrial PCBs. In ACHS I, PFAS analytes correlated more closely with industrial PCBs and chlorinated pesticides.ConclusionsParticipants in the Anniston Community Health Surveys have higher levels of PFOS and PFNA than the general population with average PFOS levels >3 times contemporaneous NHANES levels. Since PFAS were not known to be manufactured in the area, more work needs to be completed to determine if population demographics, proximity to a military base, or regional manufacturing can explain the elevated levels.