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Environmental mixtures and breast cancer: identifying co-exposure patterns between understudied vs breast cancer-associated chemicals using chemical inventory informatics

Abstract

Background

Although evidence linking environmental chemicals to breast cancer is growing, mixtures-based exposure evaluations are lacking.

Objective

This study aimed to identify environmental chemicals in use inventories that co-occur and share properties with chemicals that have association with breast cancer, highlighting exposure combinations that may alter disease risk.

Methods

The occurrence of chemicals within chemical use categories was characterized using the Chemical and Products Database. Co-exposure patterns were evaluated for chemicals that have an association with breast cancer (BC), no known association (NBC), and understudied chemicals (UC) identified through query of the Silent Spring Institute’s Mammary Carcinogens Review Database and the U.S. Environmental Protection Agency’s Toxicity Reference Database. UCs were ranked based on structure and physicochemical similarities and co-occurrence patterns with BCs within environmentally relevant exposure sources.

Results

A total of 6793 chemicals had data available for exposure source occurrence analyses. 50 top-ranking UCs spanning five clusters of co-occurring chemicals were prioritized, based on shared properties with co-occuring BCs, including chemicals used in food production and consumer/personal care products, as well as potential endocrine system modulators.

Significance

Results highlight important co-exposure conditions that are likely prevalent within our everyday environments that warrant further evaluation for possible breast cancer risk.

Impact statement

Most environmental studies on breast cancer have focused on evaluating relationships between individual, well-known chemicals and breast cancer risk. This study set out to expand this research field by identifying understudied chemicals and mixtures that may occur in everyday environments due to their patterns of commercial use. Analyses focused on those that co-occur alongside chemicals associated with breast cancer, based upon in silico chemical database querying and analysis. Particularly in instances when understudied chemicals share physicochemical properties and structural features with carcinogens, these chemical mixtures represent conditions that should be studied in future clinical, epidemiological, and toxicological studies.

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Fig. 1: Schematic for ranking of UCs based potential for influencing breast cancer risk.
Fig. 2: Translating chemical use inventory data to inform human exposure patterning.
Fig. 3: Clusters of chemicals arranged by human use patterns.
Fig. 4: Top ten understudied chemicals (UCs) in each cluster of interest.

Data availability

All data used for these analyses are publicly available, either through CPDat [16] ToxRefDB [19], or the CompTox Chemicals Dashboard [22]. Script associated with these analyses are publicly available through the Ragerlab Github repository [59]. Data that were combined and analyzed in generating results for this specific study are provided as supplemental material (Supplementary Tables 110, provided online through the Ragerlab-Dataverse repository [41]).

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Acknowledgements

The research described in this manuscript has been reviewed by the Center for Computational Toxicology and Exposure, U.S. EPA, and approved for publication. Approval does not signify that contents necessarily reflect the views and policies of the agency, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. The authors would like to thank Drs. Peter Egeghy and Chris Corton for providing internal technical review of this manuscript.

Funding

This study was supported by the Institute for Environmental Health Solutions (IEHS) at the Gillings School of Global Public Health, RFA-18-01, ‘Identifying solutions that optimize the health of cancer survivors’, and through the National Institutes of Health (NIH) from the National Institute of Environmental Health Sciences, including grant funds (P42ES031007). Support was also provided by the Intramural Research Program of the Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.

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LEK, KLD, KPM, KKI, and JER were responsible for the overall research design. LEK and JER were responsible for data analyses. LEK, KLD, KPM, and KKI were responsible for data extraction and organization from utilized databases. LEK and JER were responsible for manuscript drafting. All study coauthors reviewed manuscript text and provided scientific feedback.

Corresponding author

Correspondence to Julia E. Rager.

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Koval, L.E., Dionisio, K.L., Friedman, K.P. et al. Environmental mixtures and breast cancer: identifying co-exposure patterns between understudied vs breast cancer-associated chemicals using chemical inventory informatics. J Expo Sci Environ Epidemiol (2022). https://doi.org/10.1038/s41370-022-00451-8

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  • DOI: https://doi.org/10.1038/s41370-022-00451-8

Keywords

  • Cancer
  • Co-exposures
  • Environmental Chemicals
  • Mixtures
  • Informatics
  • ExpoCast

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