ABSTRACT
The emerging sex difference in the incidence of colon cancer, and the available data on the negative association between the incidence of colon malignancy and parity, led McMichael and Potter to formulate a hypothesis on the relationship between sex steroid exposure and the incidence of colon cancer, which was based on qualitative and quantitative alterations in bile acid composition. The enzyme complex aromatase, cytochrome P450 aromatase, transforms androgenic precursors into estrogenic compounds, and is expressed in normal colonic epithelium and in colon cancer cell lines. The observation that ‘methylation imbalance’ may fundamentally contribute to tumor progression has been documented in the tissues of numerous malignancies and in neoplastic cell lines of animal and human cancers. Methylation-associated loss of expression of the estrogen receptors gene results in deregulation of growth in cultured colonic tumor cells, and may offer an alternative mechanism to mutation in inactivating tumor suppressor genes.
