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Environmental factors influencing hormone receptor positive breast cancer incidence: integrating chemical signatures from dust wipes with self-reported sources of exposure

Journal of Exposure Science & Environmental Epidemiology (2025)Cite this article

Abstract

Background

Breast cancer is a highly prevalent disease. Chemical exposures may contribute to breast cancer risk, though most chemicals to which humans are exposed remain understudied in breast cancer research.

Objective

This study tested the hypothesis that environmental chemicals present in households of women who do and do not develop breast cancer will have differential abundance, and that chemical profiles relate to self-reported sources of exposures.

Methods

Household dust wipe samples were collected at enrollment in the Sister Study cohort in 2003–2009. We evaluated a subsample of Sister Study participants who developed hormone receptor positive breast cancer within 10 years after enrollment (N = 40, “cases”) and who remained breast cancer free during the same period (N = 40, “controls”). Dust wipes were analyzed via liquid chromatography with tandem mass spectrometry coupled with database mining approaches. Participants self-reported personal care product usage and proximity to environmental pollution sources. Frequent itemset mining (FIM) was used to evaluate chemical occurrence and associations with questionnaire data.

Results

In the dust wipe samples, there were 189 features annotated to potential chemicals that significantly differed (adjusted p < 0.1) in abundance between cases and controls. Example chemicals included suspected endocrine disruptors 23-(Nonylphenoxy)-3,6,9,12,15,18,21-heptaoxatricosan-1-ol, triethanolamine, and thiabendazole. Analysis of questionnaire data identified the chemical 6-benzyl-2-[bis[(2S)-2-aminopropanoyl]amino]-3-methylphenyl] (2S)-2-[[(2S)-2-(3-hydroxyhexanoylamino)-3-methylbutanoyl]amino]-3-methylbutanoate to be of high interest due to its link, derived through FIM, to 45 exposure scenarios, largely described by elevated personal care product usage habits.

Significance

Overall, this study builds the evidence base for understudied chemicals in everyday household environments that may alter breast cancer risk. Coupling chemical analysis results with participant survey data highlighted behaviors and environmental factors that may influence exposures to these chemicals, informing the design of future investigations to better understand sources of breast cancer risk in women.

Impact

  • There is much to understand about household exposures that can affect breast cancer risk. This study aimed to generate a novel household exposomic dataset leveraging dust wipe samples from the Sister Study cohort. A subset of the detected chemicals was found to be differentially detected in the houses of women who developed breast cancer. Additional analysis of self-reported questionnaire data demonstrated linkages between increased personal care product usage and elevated chemical abundance. The results of this study lend important insights into understudied chemicals in the home that may alter breast cancer risk and possible sources of exposure to these substances.

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Fig. 1: Overall non-targeted analysis workflow, data filtering, and data processing steps to prioritize features extracted from household dust wipes for chemical characterization through MS2.
Fig. 2: Relative abundance of molecular features annotated to chemicals detected in household dust wipe samples from a total of 80 samples collected in the Sister Study cohort.
Fig. 3: The breakdown of types of questions from the questionnaire data considered during the frequent itemset mining analysis and the number of each category present in at least one of the 213 association rules.
Fig. 4: Balloon plot showing association rules derived using frequent itemset mining analysis for the chemical that was a part of the most rules [45].
Fig. 5: Balloon plots showing association rules derived using frequent itemset mining analysis for the exposure scenarios associated with the most unique chemicals [6].

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Data availability

All data, analysis scripts, and results from this analysis are publicly available. Analysis scripts, datasets, and results are organized on the Rager lab Github site (https://github.com/Ragerlab) and Dataverse (https://dataverse.unc.edu/dataverse/ragerlab).

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Funding

This study was supported by research grants from the National Institutes of Health (NIH) training grant (T32ES007018) and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS) (Z01 ES 044005 to DPS and Z1AES103332 to AJW). Additional support was provided by the Institute for Environmental Health Solutions at the Gillings School of Global Public Health.

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Authors and Affiliations

  1. Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA

    Lauren E. Koval, Yun-Chung Hsiao, Ellie Jiang, Lauren Eaves, Kun Lu & Julia E. Rager

  2. The Institute for Environmental Health Solutions, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA

    Lauren E. Koval, Yun-Chung Hsiao, Lauren Eaves, Kun Lu & Julia E. Rager

  3. Epidemiology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

    Dale P. Sandler & Alexandra J. White

  4. Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA

    Hazel B. Nichols

  5. Curriculum in Toxicology and Environmental Medicine, UNC School of Medicine, Chapel Hill, NC, USA

    Julia E. Rager

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  1. Lauren E. Koval
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Contributions

LEK: Conceptualization, data curation, formal analysis, investigation, methodology, software, validation, visualization, writing—original draft, review and editing; YH: Formal analysis, investigation, methodology, software, validation, writing—review and editing; EJ: Formal analysis, investigation, software, validation, writing—review and editing; LAE: Investigation, methodology, software, validation, visualization, writing—review and editing; DPS: Conceptualization, funding acquisition, investigation, methodology, project administration, supervision, validation, writing—review and editing; HBN: Conceptualization, funding acquisition, investigation, methodology, project administration, supervision, validation, writing—original draft, review and editing; KL: Conceptualization, investigation, methodology, software, validation, writing—review and editing; AJW: Conceptualization, funding acquisition, investigation, methodology, project administration, supervision, validation, writing—original draft, review and editing, JER: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, software, supervision, validation, visualization, writing—original draft, review and editing.

Corresponding author

Correspondence to Julia E. Rager.

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All participants provided written informed consent. All study activities were approved by National Institutes of Health (NIH) Institutional Review Board and performed in accordance with the relevant guidelines and regulations.

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Koval, L.E., Hsiao, YC., Jiang, E. et al. Environmental factors influencing hormone receptor positive breast cancer incidence: integrating chemical signatures from dust wipes with self-reported sources of exposure. J Expo Sci Environ Epidemiol (2025). https://doi.org/10.1038/s41370-025-00819-6

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