Early Evidence from Occupational Studies
The strongest early evidence linking PFAS to kidney cancer came from studies of workers at DuPont’s Washington Works plant in West Virginia and at 3M’s facilities in Decatur, Alabama. These occupationally exposed populations showed elevated rates of kidney cancer compared to unexposed workers and general population controls. DuPont’s own internal research, later disclosed in litigation, identified the kidney cancer association decades before public acknowledgment.
Population-Level Epidemiology
Studies of communities with PFAS-contaminated drinking water — including residents served by the Pease Air National Guard Base water system in New Hampshire — have found elevated kidney cancer rates. Prospective cohort studies using stored blood samples have found dose-response relationships between baseline PFAS serum levels and subsequent kidney cancer diagnosis. The relative risk associated with elevated PFAS exposure is estimated at 1.3 to 1.7 times baseline kidney cancer rates in several analyses.
Biological Mechanisms Under Investigation
Several mechanisms may explain the kidney cancer association. PFAS accumulates in the kidney as an excretion pathway, creating high local tissue concentrations. Research has identified DNA damage, oxidative stress, and disruption of peroxisome proliferator-activated receptor (PPAR) signaling pathways as potential mechanisms. PPAR activation by PFAS compounds is particularly implicated, as PPAR pathways regulate cell growth and metabolism in kidney tissue.
Classification by Health Agencies
The International Agency for Research on Cancer (IARC) classified PFOA as a Group 1 carcinogen (carcinogenic to humans) in 2023, with kidney cancer as one of the sufficient evidence endpoints. PFOS received a Group 2A classification (probably carcinogenic). These classifications inform risk assessments underlying EPA and state drinking water regulations, and provide a scientific basis for treating PFAS reduction as a cancer prevention measure.