Role of Bisphenol A in the Development and Progression of Colorectal Cancer: Possible Sex-Specific Effects of Endogenous and Exogenous Estrogens.

Background: Colorectal cancer (CRC) is more prevalent in men, and premenopausal women have a better prognosis than both men and postmenopausal women, suggesting a protective effect of estrogen. Humans are exposed to estrogen-like contaminants such as bisphenol A (BPA), a chemical used in the production of plastics that has been linked to hormone-related malignancies (e.g., breast, ovarian, and prostate cancers). The natural flavonolignan compound silibinin (SIL), acting as an estrogen agonist, may play a protective role in CRC in one or both sexes. Objectives: To explore the possible association between BPA and CRC, focusing on its potential pro-tumor role and possible gender differences. Analyzing the possible protective effects of SIL on the development of CRC is the secondary objective of the project. Methods: To shed light on the interaction between sex and estrogens, both endogenous and exogenous, in the onset of CRC. To this end, we combined ex vivo, in vitro, and in vivo approaches to deepen our understanding of the molecular mechanisms involved. Conclusions: The data provided by this study will contribute to understanding the role of estrogens and their receptors in the onset and progression of CRC and the potential protective role of SIL in both sexes.