AS679 - Perfluoroalkyl Substances (PFAS) and liver cancer risk in the United States

Investigator Names and Contact Information

Xuehong Zhang (xuehong.zhang@yale.edu)

Introduction/Intent

In the US, the reasons for the 3-fold increase in liver cancer incidence remain poorly understood. At the same time, there is a widespread increasing concern about the potential role of environmental exposures to PFASs on human liver cancer risk. A link between environmental exposure to PFASs and liver cancer risk is biologically plausible and strongly supported by experimental and retrospective cohort mortality studies of occupationally exposed workers to PFAS contamination. To date, however, large and high-quality prospective cohort studies of un-occupationally exposed populations have yet to be conducted to either confirm or refute these retrospective findings concerning PFASs. This proposed study represents the first prospective population-based epidemiological study to investigate the association between PFAS exposure and liver cancer risk in the US population. The findings of this proposed study would fundamentally advance our knowledge of liver cancer etiology and can help regulators make sound, science-based decisions, inform the medical and public health communities about the potential health effects of PFASs exposure, and eventually lead to improved prevention of this deadly disease if the association of interest is substantiated.

The Specific Aims of this study are:

Aim 1. To characterize the associations between circulating levels of PFASs and liver cancer risk in a nested case-control study of 600 incident liver cancer cases, and 1200 healthy controls. We hypothesize that: Higher circulating levels of PFASs, especially PFOA and PFOA that showed an increased risk of liver cancer in experimental studies, are associated with higher risk of developing liver cancer.

Aim 2. To determine whether risk of liver cancer associated with environmental PFAS exposure varies by mixture and types of PFASs. We hypothesize that: A synergism exists among the PFAS mixtures on liver cancer risk, and branched and linear PFASs that showed different bio-accumulation ability and eco-toxicity in lab studies confer different liver cancer risk.

Aim 3. Estimate the associations between PFAS levels and survival among patients with liver cancer. We hypothesize that: Higher circulating levels of PFAS are associated higher risk of liver cancer mortality.

Note: ALT and uric acid was run under study AS689 and has been uploaded under study AS689.