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 6,793 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.

Suspect Screening Analysis of Pooled Human Serum Samples Using GC × GC/TOF-MS

“…Systematic approaches are needed for annotating and querying existing information to link identified substances in biological samples to upstream exogenous exposure sources and downstream endogenous biological pathways. Efforts in EPA’s Office of Research and Development are underway to harmonize and organize information on chemical use, ,, release, and occurrence . These data repositories provide a body of evidence for the development of source hypotheses.…”

Wildfire Variable Toxicity: Identifying Biomass Smoke Exposure Groupings through Transcriptomic Similarity Scoring

“…Alternative binary similarity indices could also be employed as the field continues to expand upon toxicology-relevant similarity scoring metrics. The Jaccard index was used here due to its recognized interpretability and utility across chemical structure similarity analyses, , as well as more recent analyses on transcriptomics and mixtures exposure patterns . Other possible metrics to consider in future analyses include simple matching and Sokal–Sneath 2, which have been shown as viable options in fingerprint-based analyses. , Toxicological endpoints could also be expanded upon since wildfire exposures have been linked to a variety of health outcomes besides the included pulmonary-based responses. ,− It will be interesting to evaluate whether similar exposure groupings occur when evaluating these different outcomes and associated toxicological targets.…”

“…The Jaccard index was used here due to its recognized interpretability and utility across chemical structure similarity analyses, 33,34 as well as more recent analyses on transcriptomics 18 and mixtures exposure patterns. 53 Other possible metrics to consider in future analyses include simple matching and Sokal−Sneath 2, which have been shown as viable options in fingerprint-based analyses. 32,54 Toxicological endpoints could also be expanded upon since wildfire exposures have been linked to a variety of health outcomes besides the included pulmonary-based responses.…”

m6A readers, writers, erasers, and the m6A epitranscriptome in breast cancer

“…Whether m6A is 'hard wired' by the RRACH motif (Darnell et al 2018) or modified depending on regulation of the METTL3 complex, other RNA-binding proteins, RNA structure, intranuclear localization, for example, condensates, and the epigenome remain to be examined in a cell-and tissue-type manner in BC. How the 'expososome', including the microbiome, environmental chemical exposures, and endocrine-and metabolismdisrupting chemicals (Koual et al 2020, Koval et al 2022, affect these events to regulate the epitranscriptome in BC is unknown. The advent of direct RNA sequencing and single-cell RNA sequencing promises to yield new understanding of epitranscriptomics not only of m6A but less abundant modifications in BC progression, endocrine therapy resistance, and metastasis.…”