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Among women, breast cancer is the most prevalent form of cancer worldwide and has the second highest mortality rate of any cancer in the United States. The breast cancer related death rate is 40 % higher in non-Hispanic Black women compared to non-Hispanic White women. The incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer for which there is no targeted therapy, is also approximately three times higher for Black, relative to, White women. The drivers of these differences are poorly understood. Here, we aimed to identify chemical exposures which play a role in breast cancer disparities. Using chemical biomonitoring data from the National Health and Nutrition Examination Survey (NHANES) and biological activity data from the EPA's ToxCast program, we assessed the toxicological profiles of chemicals to which US Black women are disproportionately exposed. We conducted a literature search to identify breast cancer targets in ToxCast to analyze the response of chemicals with exposure disparities in these assays. Forty-three chemical biomarkers are significantly higher in Black women. Investigation of these chemicals in ToxCast resulted in 32,683 assays for analysis, 5172 of which contained nonzero values for the concentration at which the dose-response fitted model reaches the cutoff considered "active". Of these chemicals BPA, PFOS, and thiram are most comprehensively assayed. 2,5-dichlorophenol, 1,4-dichlorobenzene, and methyl and propyl parabens had higher biomarker concentrations in Black women and moderate testing and activity in ToxCast. The distribution of active concentrations for these chemicals in ToxCast assays are comparable to biomarker concentrations in Black women NHANES participants. Through this integrated analysis, we identify that multiple chemicals, including thiram, propylparaben, and p,p' DDE, have disproportionate exposures in Black women and have breast cancer associated biological activity at human exposure relevant doses.

Titel:	Identifying the link between chemical exposures and breast cancer in African American women via integrated in vitro and exposure biomarker data.
Autor/in / Beteiligte Person:	Polemi, KM ; Nguyen, VK ; Heidt, J ; Kahana, A ; Jolliet, O ; Colacino, JA
Zeitschrift:	Toxicology, Jg. 463 (2021-11-01), S. 152964
Veröffentlichung:	Limerick : Elsevier ; <i>Original Publication</i>: Amsterdam. Elsevier/North-Holland., 2021
Medientyp:	academicJournal
ISSN:	1879-3185 (electronic)
DOI:	10.1016/j.tox.2021.152964
Schlagwort:	Biomarkers metabolism Environmental Exposure adverse effects Female Humans Nutrition Surveys Triple Negative Breast Neoplasms epidemiology United States epidemiology White People statistics & numerical data Black or African American statistics & numerical data Breast Neoplasms epidemiology Hazardous Substances toxicity Health Status Disparities
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Toxicology] 2021 Nov; Vol. 463, pp. 152964. <i>Date of Electronic Publication: </i>2021 Sep 30. MeSH Terms: Health Status Disparities* ; Black or African American / statistics & numerical data ; Breast Neoplasms / epidemiology ; Hazardous Substances / *toxicity ; Biomarkers / metabolism ; Environmental Exposure / adverse effects ; Female ; Humans ; Nutrition Surveys ; Triple Negative Breast Neoplasms / epidemiology ; United States / epidemiology ; White People / statistics & numerical data References: NPJ Breast Cancer. 2017 Feb 27;3:5. (PMID: 28649645) ; Integr Biol (Camb). 2015 Oct;7(10):1120-34. (PMID: 25959051) ; J Hazard Mater. 2019 Feb 15;364:332-338. (PMID: 30384243) ; Environ Sci Technol. 2019 Jun 18;53(12):7045-7054. (PMID: 31081622) ; Biochem Pharmacol. 2013 Sep 1;86(5):561-70. 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(PMID: 25673085) Grant Information: T32 GM007499 United States GM NIGMS NIH HHS; P30 CA046592 United States CA NCI NIH HHS; R01 ES028802 United States ES NIEHS NIH HHS; P30 ES017885 United States ES NIEHS NIH HHS; T32 ES007062 United States ES NIEHS NIH HHS Contributed Indexing: Keywords: Breast cancer; Carcinogenesis; Chemical prioritization; Racial disparities; ToxCast Substance Nomenclature: 0 (Biomarkers) ; 0 (Hazardous Substances) Entry Date(s): Date Created: 20211002 Date Completed: 20211228 Latest Revision: 20240214 Update Code: 20240214 PubMed Central ID: PMC8593892

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Identifying the link between chemical exposures and breast cancer in African American women via integrated in vitro and exposure biomarker data.