In a recent study published in Environmental Health Perspectives, researchers delved into the genotoxicity of potentially carcinogenic chemicals and their role in inducing mammary tumours and activating progesterone or estradiol signalling. The study aimed to pinpoint chemicals that could pose a breast cancer risk to humans.
Breast cancer stands as the most prevalent form of cancer globally and a leading cause of cancer-related deaths in women. In the United States, women face double the lifetime risk of developing breast cancer compared to lung cancer. Notably, the incidence of breast cancer among younger women is on the rise, with mortality rates in the 20 to 49 age group being double that of other cancers affecting both sexes. To mitigate breast cancer risk, identifying potentially carcinogenic or mammary tumour-inducing chemicals that cause endocrine disruption or genotoxicity is crucial. Animal models, particularly rodents with similar tissue structures and pathways as humans, play a pivotal role in identifying potentially carcinogenic chemicals.
Using databases like the International Agency for Research on Cancer (IARC) and ToxCast from the U.S. Environmental Protection Agency, researchers identified chemicals with mammary tumor-inducing and endocrine-disrupting abilities. These chemicals were evaluated based on key characteristics such as genotoxicity and endocrine activity strength to predict their mammary tumour-inducing potential.
Key characteristics, including genotoxicity, cell proliferation, signalling alterations, inflammation, epigenetic modifications, and immunosuppression, were considered. The presence of these characteristics indicated potential carcinogenic activity. For breast cancer, hormone receptor activity and endocrine signalling are crucial. The study identified 279 mammary carcinogens and 642 chemicals stimulating progesterone or estrogen signalling, totalling 921 breast cancer-relevant exposures. Key characteristics like genotoxicity, estrogen receptor agonism, and steroidogenicity were enriched in mammary carcinogens, reinforcing their predictive efficacy.
The findings underscore the importance of the key characteristics framework in identifying potential mammary carcinogens. With 921 identified chemicals posing breast cancer risk, the study emphasizes the need for improved assessment methods and assays to test mammary-tumor-inducing abilities and reduce exposures.
