Abstract
BackgroundPerfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population.MethodsParticipants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review.ResultsCRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend < 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10–15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels.ConclusionsIn this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis.
Highlights
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC)
The role of peroxisome proliferator-activated receptor-γ (PPAR-γ) in adipocyte differentiation, the antiproliferative and/or differentiating effects of Peroxisome proliferator-activated receptors (PPARs)-α and PPAR-γ ligands in human colon and other tumor cell lines, and the anticancer effects of both PPAR isotypes in animal models of CRC support a chemoprotective role for these nuclear hormone receptors [10,11]
Associations of CRC to the 5 additional PFCs were inconsistent, with 2 (C6, C10) showing significant positive associations (p < 0.001), 2 (C6s, C9) showing significant inverse associations (p ≤ 0.01), and one (C7) showing no association (p = 0.7) with CRC. To our knowledge, this is the first large, communitybased study to examine the potential links between CRC and environmental perfluoroalkyl acids (PFAAs), and the first to examine in detail the association of CRC to PFOA and PFOS
Summary
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). The link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. While incidence and mortality rates of colorectal cancer (CRC) have declined during the past decade, CRC remains the third most common cancer in both men and women and the third leading cause of cancer-related mortality in the United States [1,2]. Certain lifestyle-related factors increase risk for CRC, including physical inactivity, obesity, smoking, and a diet high in red and processed meats [2,3]. Recent cohort studies suggest constipation may increase CRC risk [4,5]. The role of peroxisome proliferator-activated receptor-γ (PPAR-γ) in adipocyte differentiation, the antiproliferative and/or differentiating effects of PPAR-α and PPAR-γ ligands in human colon and other tumor cell lines, and the anticancer effects of both PPAR isotypes in animal models of CRC support a chemoprotective role for these nuclear hormone receptors [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
