Circulating per- and polyfluoroalkyl substances and liver cancer risk: a nested case-control analysis of individual participant data from 12 prospective cohorts.

Authors

Watling CZ, Petrick JL, Graubard BI, Zhang X, Barnett MJ, Buring JE, Chen Y, Eliassen AH, Gaziano M, Kang JH, Koshiol J, Huang WY, Lee IM, Moore SC, Mucci LA, Neuhouser ML, Newton CC, Palmer JR, Rosenberg L, Sesso HD, ...show more Shrubsole M, Tinker L, Triplette M, Um CY, Visvanathan K, Wactawski-Wende J, Willett W, Wu F, Zheng W, Hofmann J, Purdue MP, Campbell PT, Barupal D, McGlynn KA

Affiliations

• Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
• Slone Epidemiology Center, Boston University, Boston, MA, USA.
• School of Nursing, Yale University, Orange, CT, USA.
• Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
• Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
• Departments of Population Health and Environmental Medicine, NYU Grossman School of Medicine, New York, NY, USA.
• Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
• Department of Population Science, American Cancer Society, Atlanta, GA, USA.
• Department of Medicine, Harvard Medical School, Boston, MA, USA.
• Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.

Abstract

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been associated with numerous deleterious health outcomes including liver damage. However, whether exposure to PFAS is associated with liver cancer risk remains unclear.

METHODS: We conducted a matched nested case-control study among 12 prospective cohort studies located in the United States. Pre-diagnostic PFAS, namely perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS), were measured from blood samples among 853 individuals who developed liver cancer and 853 matched control participants. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable-adjusted conditional logistic regression for liver cancer risk by study-specific quartiles of concentrations and per 90^th vs. 10^th percentile incremental increase.

RESULTS: In the main multivariable-adjusted model, circulating PFOS, PFOA, and PFHxS levels were not associated with liver cancer risk (OR per 90^th vs. 10^th percentile increase: 1.00, 95% CI: 0.79-1.28; 0.92, 0.73-1.15; and 0.95, 0.75-1.21, respectively). However, when analyses were stratified by sex, PFOA concentrations were positively associated with liver cancer risk in males (OR per 90^th vs. 10^th percentile increase: 1.62 95% CI:1.07-2.45), whereas an inverse association was observed amongst females (OR per 90^th vs. 10^th percentile increase:0.68, 0.50-0.92; p-interaction=0.005). Analyses separating liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma, showed no evidence of heterogeneity, although associations were stronger but not significant for HCC. No evidence of interaction was observed by time to diagnosis, time period of blood draw, body mass index, alcohol intake, ethnicity, or diabetes status.

CONCLUSIONS: In the largest study to date, none of the measured circulating PFAS were associated with liver cancer risk; however, PFOA associations appeared to differ by sex and further research is needed to explore these apparent differences by sex. https://doi.org/10.1289/EHP16980.