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

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.

A comprehensive analysis of racial disparities in chemical biomarker concentrations in United States women, 1999-2014.

BACKGROUND: Stark racial disparities in disease incidence among American women remain a persistent public health challenge. These disparities likely result from complex interactions between genetic, social, lifestyle, and environmental risk factors. The influence of environmental risk factors, such as chemical exposure, however, may be substantial and is poorly understood. OBJECTIVES: We quantitatively evaluated chemical-exposure disparities by race/ethnicity, life stage, and time in United States (US) women (n = 38,080) by using biomarker data for 143 chemicals from the National Health and Nutrition Examination Survey (NHANES) 1999-2014. METHODS: We applied a series of survey-weighted, generalized linear models using data from the entire NHANES women population along with cycle and age-group stratified subpopulations. The outcome was chemical biomarker concentration, and the main predictor was race/ethnicity with adjustment for age, socioeconomic status, smoking habits, and NHANES cycle. RESULTS: Compared to non-Hispanic White women, the highest disparities were observed for non-Hispanic Black, Mexican American, Other Hispanic, and Other Race/Multi-Racial women with higher levels of pesticides and their metabolites, including 2,5-dichlorophenol, o,p'-DDE, beta-hexachlorocyclohexane, and 2,4-dichlorophenol, along with personal care and consumer product compounds, including parabens and monoethyl phthalate, as well as several metals, such as mercury and arsenic. Moreover, for Mexican American, Other Hispanic, and non-Hispanic black women, there were several exposure disparities that persisted across age groups, such as higher 2,4- and 2,5-dichlorophenol concentrations. Exposure levels for methyl and propyl parabens, however, were the highest in non-Hispanic black compared to non-Hispanic white children with average differences exceeding 4-fold. Exposure disparities for methyl and propyl parabens are increasing over time in Other Race/Multi-Racial women while fluctuating for non-Hispanic Black, Mexican American, and Other Hispanic. Cotinine levels are among the highest in Non-Hispanic White women compared to Mexican American and Other Hispanic women with disparities plateauing and increasing, respectively. DISCUSSION: We systematically evaluated differences in chemical exposures across women of various race/ethnic groups and across age groups and time. Our findings could help inform chemical prioritization in designing epidemiological and toxicological studies. In addition, they could help guide public health interventions to reduce environmental and health disparities across populations.