Perfluoroalkyl substances and risk of kidney cancer in US men and women - Abstract PFAS are a class of man-made organofluorine compounds whose presence in the environment is an
emerging, worldwide public health concern and a priority in environmental and human health research. Many
PFAS are environmentally persistent, bioaccumulative, and have long half-lives in humans. Of particular concern
is that environmental exposure to PFAS may increase the risk of kidney cancer, whose incidence has shown
unexplained sustained and rapid increases in the US during the past decades. Several lines of emerging
evidence strongly support that PFAS exposures may increase the risk of kidney cancer among humans: First,
the kidney is a target organ of PFAS, which cause serious damage to the kidney at the levels commonly
experienced by US population; Second, PFAS exposures have been associated with kidney damage that is
known to increase kidney cancer risk; Third, a recent population-based case-control study of 324 RCC cases
and 324 controls from NCI supports the findings of early occupational mortality studies that PFAS exposure
increases kidney cancer risk. Much larger prospective studies of diverse, non-occupationally exposed
populations are urgently needed to either confirm or refute these preliminary findings.
Here, we propose a prospective nested case-control study to test the association between PFAS exposure and
renal cell carcinoma (RCC, more than 85% of all cases of kidney cancer). We will utilize the extensive resources
from five large and well-characterized US prospective cohorts: The Southern Community Cohort Study;
Hispanic
Community Health Study/Study of Latinos Cohort;
Nurses’ Health Study; Health Professionals Follow-Up Study;
and Physicians' Health Study. We will measure pre-diagnostic plasma levels of 40 PFAS from ~650 incident
RCC cases and their individually matched controls (~1,300 controls in 1:2 ratio). Specifically, we will examine
the following hypotheses: 1. Environmental exposure to PFAS increases the risk of RCC. In particular,
environmental exposure to PFOA, PFOS and PFHxS increases RCC risk; 2. Risk of RCC associated with
environmental PFAS exposure varies by mixture patterns, and varies by PFAS chemical structure,
branched vs linear isomers, and short vs. long chain length; and 3. Established baseline risk factors of
RCC (hypertension, obesity, diabetes and smoking) moderate the relationship between PFAS exposure
and risk of RCC. In exploratory aims, we will test if the risk of RCC associated with individual PFAS
exposures varies by histologic type of RCC or by race, and thus may contribute to racial disparities in
kidney cancer risk. This proposed study fills a critical knowledge gap and represents the first large prospective
cohort study to investigate the alleged association between PFAS exposure and kidney cancer risk in the US
among diverse cohorts of non-occupationally exposed individuals. The results of the study will inform the medical
and public health communities about the potential health effects of PFAS exposure and can help regulators make
sound, science-based decisions.
