Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study

Jongeun Rhee; Vicky C Chang; Iona Cheng; Antonia M Calafat; Julianne Cook Botelho; Joseph J Shearer; Joshua N Sampson; Veronica Wendy Setiawan; Lynne R Wilkens; Debra T Silverman; Mark P Purdue; Jonathan N Hofmann

doi:10.1016/j.envint.2023.108197

Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study

Environ Int. 2023 Oct:180:108197. doi: 10.1016/j.envint.2023.108197. Epub 2023 Sep 14.

Affiliations

¹ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
² Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
³ Organic Analytical Toxicology Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁴ Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁵ Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
⁶ Department of Population and Public Health Sciences and Norris Comprehensive Cancer Center, University of Southern California, CA, USA.
⁷ Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, Honolulu, HI, USA.
⁸ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. Electronic address: hofmannjn@mail.nih.gov.

PMID: 37741007
DOI: 10.1016/j.envint.2023.108197

Abstract

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993-2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, OR_continuous = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), P_trend = 0.04; OR_continuous = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [OR_continuous = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations.

Keywords: Kidney cancer; Multiethnic cohort; Per- and polyfluoroalkyl substances (PFAS); Perfluorononanoate (PFNA); Perfluorooctanoate (PFOA); Renal cell carcinoma.

Published by Elsevier Ltd.

MeSH terms

Adult
Alkanesulfonic Acids*
Caprylates*
Carcinoma, Renal Cell* / epidemiology
Case-Control Studies
Cohort Studies
Environmental Pollutants*
Female
Fluorocarbons*
Humans
Kidney Neoplasms* / epidemiology
Male

Substances

Alkanesulfonic Acids
Caprylates
Environmental Pollutants
Fluorocarbons
hexadecafluoro-nonanoic acid
perfluorooctanoic acid

Grants and funding

U01 CA164973/CA/NCI NIH HHS/United States