Abstract C035: Impact of South Florida environmental chemicals on breast cells derived from women of different ancestries

Abstract

Abstract Breast Cancer (BC) occurrence is due to an interplay of ancestry-based and environmental factors. In order to study BC disparities in South Florida, our group initially focused on 7 Broward County zip codes where the proportion of BC identified at late stage is much higher (55%) than the national average (30-35%), and where there is a high percentage of people of African Ancestry (AA). Thus, we are investigating the interaction of ancestry and the environment in BC. Our hypothesis is that there are unique environmental sensitivities leading to BC that are associated with specific ancestral groups. We expect that some of the carcinogenic chemicals that cause BC may cause more advanced or aggressive BC in AA women. We are studying 2 environmental pollutants, one in water (arsenic) and one in soil (glyphosate) that are prevalent in S. Florida, and these local zip codes, and analyze the specific impact of these pollutants on unique breast reduction mammoplasty cultures derived from women of AA vs. Non-Hispanic White (NHW) ancestry. We have developed a unique tissue engineering system for non-diseased breast that allows us to establish cultures with high success (95%) using a stem cell-based medium and Matrigel. From primary cultures, we have established 38 extended explants (<13 passages) or cell lines (>13 passages). 10 are from AA women and 28 are from women of NHW ancestry, thus far with Hispanic samples in the works. We hypothesize that these groups will show significant differences in their gene expression patterns after exposure to environmental carcinogens. We have previously shown that there is a significantly higher proportion of breast stem cells in AA cultures (N=5) compared with the NHW cultures (N=5) (p= 0.028). This difference in size of the stem cell compartment may help to explain why the age of breast development in these two groups is significantly different and why their subtypes of BC are different based on ancestry. We are using 5 AA and 5 NHW breast reduction mammoplasty cultures, as well as stem cells derived from them, to test arsenic and glyphosate for their ability to alter the transcriptome of these cells using RNA sequencing. Analyses of gene expression using both supervised and unsupervised strategies will be performed (KEGG Pathways and single genes). We expect to see changes that are consistent with pre-invasive malignancy that have been established in endocrine disruptor studies. Because our group is one of the few that has successfully cultured stage 0 BC (Ductal Carcinoma In Situ), we have existing databases of transcriptomic changes from 6 DCIS cell lines as well as from 6 stage I BC cell lines for comparison. Preliminary data from the Nanostring BC360 and RNA sequencing show 8 genes involved in DNA damage and repair that are downregulated in AA breast reduction mammoplasty explants relative to NHW explants. This study will fill an important void in our understanding of how the environment affects pre-cancerous development in specific demographic populations. Citation Format: Jean J. Latimer, Yousef N. Alharbi, Colton R. Simmons, Stephen E. Zimberg, Essie K. Yates. Impact of South Florida environmental chemicals on breast cells derived from women of different ancestries [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C035.