Adverse outcome pathway from activation of the AhR to breast cancer-related death. (July 2022)

• Record Type: Journal Article
• Authors: Benoit, Louise; Jornod, Florence; Zgheib, Elias; Tomkiewicz, Celine; Koual, Meriem; Coustillet, Thibaut; Barouki, Robert; Audouze, Karine; Vinken, Mathieu; Coumoul, Xavier
• Is Part Of: Environment international. Volume 165(2022)
• Publication Date: 2022-07
• Subjects: Mammary metastasis -- Aryl hydrocarbon receptor -- Chemical toxicity -- Adverse outcome pathway -- Cancer development; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2022.107323
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: Adverse outcome pathways (AOP) link a molecular initiating event to an adverse event. The aryl hydrocarbon receptor (AhR) may be involved in breast cancer metastasis. We created an AOP connecting activation of the AhR to breast cancer related death. Artificial intelligence tools were used to collect and assess the evidence of our AOP. This AOP is essential for regulatory health issues in toxicology. Abstract: Adverse outcome pathways (AOPs) are formalized and structured linear concepts that connect one molecular initiating event (MIE) to an adverse outcome (AO) via different key events (KE) through key event relationships (KER). They are mainly used in eco-toxicology toxicology, and regulatory health issues. AOPs must respond to specific guidelines from the Organization for Economic Co-operation and Development (OECD) to weight the evidence between each KE. Breast cancer is the deadliest cancer in women with a poor prognosis in case of metastatic breast cancer. The role of the environments in the formation of metastasis has been suggested. We hypothesized that activation of the AhR (MIE), a xenobiotic receptor, could lead to breast cancer related death (AO), through different KEs, constituting a new AOP. An artificial intelligence tool (AOP-helpfinder), which screens the available literature, was used to collect all existing scientific abstracts to build a novel AOP, using a list of key words. Four hundred and seven abstracts were found containing at least a word from our MIE list and either one word from our AO or KE list. A manual curation retained 113 pertinent articles, which were also screened using PubTator. From these analyses, an AOP was created linking the activation of the AhR to breast cancer related death through decreased apoptosis, inflammation, endothelial cell migration, angiogenesis, and invasion. These KEs promote an increased tumor growth, angiogenesis and migration which leads to breast cancer metastasis and breast cancer related death. The evidence of the proposed AOP was weighted using the tailored Bradford Hill criteria and the OECD guidelines. The confidence in our AOP was considered strong. An in vitro validation must be carried out, but our review proposes a strong relationship between AhR activation and breast cancer-related death with an innovative use of an artificial intelligence literature search.