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A nested case-control study of serum levels of polyfluoroalkyl chemicals (PFCs) and renal cell carcinoma among participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Principal Investigator

Name
Jonathan Hofmann

Degrees
Ph.D.

Institution
National Cancer Institute

Position Title
Investigator

Email
hofmannjn@mail.nih.gov

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2017-0027

Initial CDAS Request Approval
Sep 28, 2017

Title
A nested case-control study of serum levels of polyfluoroalkyl chemicals (PFCs) and renal cell carcinoma among participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Summary
Per- and polyfluorinated chemicals (PFCs) have been widely used in a variety of commercial and industrial applications. Although usage has decreased since the early 2000s, PFCs resist degradation and remain detectable in approximately 98% of the U.S. population. PFCs are distributed to the kidney, liver, and serum. Serum levels of PFCs have been associated with reduced renal function in several cross-sectional studies. Occupational exposure to PFCs has been inconsistently associated with elevated kidney cancer and non-malignant kidney disease mortality. Estimated environmental exposure to perfluorooctanoic acid (PFOA), one extensively used PFC, was associated with elevated risk of kidney cancer among residents of the mid-Ohio Valley who lived near a large PFC-producing plant. PFOA is currently classified as a possible human carcinogen (group 2B) by the International Agency for Research on Cancer based on limited human and animal evidence; other PFCs with known toxicity have not been evaluated. No analytic epidemiologic studies have evaluated cancer risk and PFCs other than PFOA.
We propose to investigate the relationship between serum levels of PFCs and risk of renal cell carcinoma (RCC) in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We plan to conduct a nested case-control study of pre-diagnostic serum PFC levels in 374 RCC cases with available serum samples and 374 individually matched controls. This study will be the largest study of PFOA exposure and kidney cancer risk to date, the first to investigate associations with other PFCs, the first to directly assess exposure to these chemicals through the measurement of pre-diagnostic concentrations in serum. Given these strengths, this study has the potential to make a major contribution to our understanding of the relationship between PFC exposure and RCC risk.

Aims

1. To determine whether circulating levels of four PFCs [perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), and PFOA] in pre-diagnostic samples are associated with increased risk of developing RCC; and
2. To explore potential interactions between PFCs and subject characteristics including sex, smoking, hypertension, and body mass index.

Collaborators

Catherine Callahan (National Cancer Institute)
Jonathan Hofmann (National Cancer Institute)
Mark Purdue (National Cancer Institute)
Wen-Yi Huang (National Cancer Institute)
Joshua Sampson (National Cancer Institute)
Kyle Steenland (Emory University)
Scott Bartell (University of California, Irvine)

Approved Addenda This project has one or more approved addenda.
  • Measuring PFAS in an additional aliquot from 40 previously selected controls

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