Identifying human breast carcinogens using exposomics
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Evidence for a role of hormones in breast cancer risk and prognosis is overwhelming. The most important one is estrogen, which acts by binding to proteins in breast tissue called estrogen receptors (ER). There are chemicals in our bodies and environment that can also bind to ER but are not natural hormones. Identifying these chemicals that interact with ER in our bodies is key to designing interventions to prevent breast cancer. This is the goal of the current proposal. 
 
 
 
 
 
 Research question(s) or central hypotheses: There are chemicals present in human blood that are not natural hormones, but can bind to the estrogen receptors and thereby modulate breast cancer risk. We hypothesize that a large number of these chemicals can be identified using a combination of studies on cultured human cells in a petri dish and analytical chemistry. Once we have identified the chemicals, we intend to prioritize them and then directly test their association with breast cancer risk in a multiethnic study of San Francisco Bay Area women with breast cancer and matched control women who do not have breast cancer. 
 
 
 
 
 
 General methodology: We have refined a method that uses cultured human cells in a petri dish to screen for chemicals that interact with ER. Using blood samples from a large study of breast cancer we propose to use this method to identify groups of women with widely differing levels of chemicals that interact with ER after subtraction of the natural-hormone component (estradiol). Samples with the highest and lowest values will be studied using analytical chemistry, to identify the chemicals that cause the differences in ER activation. The identified chemicals will be tested for ER binding activity in our human cell cultures. This will create a list of those chemicals present in human blood that interact with ER at relevant concentrations. Levels of these chemicals will be measured in blood from women with breast cancer and matched control women who do not have breast cancer, and eventually in girls with differing levels of breast development. 
 
 
 
 
 
 Innovative elements: Our approach is completely novel for breast cancer and is based on the exposome concept that aims to measure exposures from all environmental sources. The innovative part of the project is that we use a validated cell culture method to screen for chemicals that are clearly important to breast cancer risk as they modulate the estrogen receptor, then use state-of-the-art analytical chemistry to identify those chemicals that mimic the natural estrogens or act as antagonists to them, by comparing people with high levels against those with low levels of chemicals. The blood samples are from a study that includes African American, Hispanic and Non-Hispanic white women, with over-representation of the two former groups. Thus, our study is largely focused on underserved populations and may help alleviate and inform about health disparities. 
 
 
 
 
 
 Advocacy involvement and relevance to the human issues associated with breast cancer: 
 
 
 
 The role of environmental chemicals in breast cancer risk and prognosis is of great concern to many advocates and community members. By working with Zero Breast Cancer, Dr. Smith and colleagues will be informed about the concerns of patients, survivors and the advocacy community, particularly the desire to identify modifiable risk factors. When results are available, Dr. Smith and colleagues will work with Zero Breast Cancer to conduct outreach and produce educational materials that will be useful for preventing breast cancer before it can start, with lay audiences and possibly policymakers.
 
 
 
 
 
 
 
 Publications: 
 
 
 
 Using exposomics to assess cumulative risks and promote health