Dataset Information

A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes.

ABSTRACT:

Background

Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations.

Objective

We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations.

Methods

In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30-65 years old and in relation to kidney function among adults > 20 years old (n = 29,499) in a highly exposed Mid-Ohio Valley cohort. Estimated glomerular filtration rate (eGFR, a marker of kidney function) and serum PFOA concentration were measured in blood samples collected during 2005-2006. Retrospective year-specific serum PFOA estimates were modeled independently of measured PFOA based on residential history and plant emissions. Using measured and modeled PFOA in 2005 or 2006 (predictor variables), cross-sectional associations were assessed for eGFR and menopause (yes/no). We also analyzed measured PFOA (dependent variable) in relation to the number of years since menopause.

Results

Menopause and eGFR were significantly associated with measured (trend tests: p = 0.013, p = 0.0005, respectively) but not with modeled serum PFOA (p = 0.50, p = 0.76, respectively). Measured PFOA levels increased for the first 7 years after menopause (trend test, p < 0.0001), providing further evidence that the observed association between measured PFOA and menopause is subject to reverse causation for this outcome.

Conclusion

Our results support the conjecture that in previous studies, earlier menopause and reduced kidney function are the causes rather than the results of increased measured serum PFOA. These results suggest caution in using biomarkers in cross-sectional studies. Citation: Dhingra R, Winquist A, Darrow LA, Klein M, Steenland K. 2017. A study of reverse causation: examining the associations of perfluorooctanoic acid serum levels with two outcomes. Environ Health Perspect 125:416-421;?http://dx.doi.org/10.1289/EHP273.

SUBMITTER: Dhingra R

PROVIDER: S-EPMC5332181 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes.

Dhingra Radhika R Winquist Andrea A Darrow Lyndsey A LA Klein Mitchel M Steenland Kyle K

Environmental health perspectives 20160816 3

<h4>Background</h4>Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations.<h4>Objective</h4>We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations. ...[more]

PMID: 27529882

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Project description:BackgroundPerfluorooctanoic acid (PFOA) has been linked to cancer in occupational mortality studies and animal toxicologic research.ObjectiveWe investigated the relationship between PFOA exposure and cancer among residents living near the DuPont Teflon-manufacturing plant in Parkersburg, West Virginia (WV).MethodsOur analyses included incident cases of 18 cancers diagnosed from 1996 through 2005 in five Ohio (OH) counties and eight WV counties. For analyses of each cancer outcome, controls comprised all other cancers in the study data set except kidney, pancreatic, testicular, and liver cancers, which have been associated with PFOA in animal or human studies. We applied logistic regression models to individual-level data to calculate adjusted odds ratios (AORs) and confidence intervals (CIs). For the combined analysis of OH and WV data, the exposure of interest was resident water district. Within OH, geocoded addresses were integrated with a PFOA exposure model to examine the relationship between cancer odds and categories of estimated PFOA serum.ResultsOur final data set included 7,869 OH cases and 17,238 WV cases. There was a positive association between kidney cancer and the very high and high serum exposure categories [AOR = 2.0 (95% CI: 1.0, 3.9) n = 9 and 2.0 (95% CI: 1.3, 3.2) n = 22, respectively] and a null association with the other exposure categories compared with the unexposed. The largest AOR was for testicular cancer with the very high exposure category [2.8 (95% CI: 0.8, 9.2) n = 6], but there was an inverse association with the lower exposure groups, and all estimates were imprecise because of small case numbers.ConclusionsOur results suggest that higher PFOA serum levels may be associated with testicular, kidney, prostate, and ovarian cancers and non-Hodgkin lymphoma. Strengths of this study include near-complete case ascertainment for state residents and well-characterized contrasts in predicted PFOA serum levels from six contaminated water supplies.

Dataset Information

A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes.

Background

Objective

Methods

Results

Conclusion

Publications

A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes.

Similar Datasets

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