**9. Acknowledgements and statement of conflict of interest**

Carol Gano is funded by an Australian Postgraduate scholarship. Prof. de Souza is a holder of a project grant from the Prostate Cancer Foundation of Australia, and a Translational Cancer Research Grant from the NSW Cancer Institute. Prof. de Souza was a consultant in 2002 for Novogen Pty Ltd, the manufacturer of phenoxodiol.

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**12** 

*Italy* 

**Phytoestrogens as Nutritional Modulators** 

**in Colon Cancer Prevention** 

*Gastroenterology Unit, Department of Emergency and* 

Michele Barone, Raffaele Licinio and Alfredo Di Leo

*Organ Transplantation (D.E.T.O.), University of Bari "A. Moro", Bari,* 

Intestinal carcinogenesis is the final outcome of a multi-step process resulting from genetic alterations that are influenced by two categories of factors: environmental factors and hostrelated factors such as cytokines and hormones (including sex steroid hormones). One of the most important environmental factors involved in the development of colon cancer is dietary components. However, variations in cancer incidence among and within populations with similar dietary patterns suggest that the predominant pathogenetic factor is the individual response, through the expression of different protein and metabolite patterns (1). Among host-related factors particular attention is paid in this work to the relationship between estrogens, as well as their agonists (phytoestrogens), and colon cancer,

Colorectal cancer (CRC) is the final outcome of a multi-step process that, in most cases,

The tumor suppressor gene mutation involving the *Adenomatous Polyposis Coli* (APC) gene is present in 80% of sporadic CRCs and 100% of cases of *Familial Adenomatous Polyposis* (FAP). In humans, the APC mutation provides the genetic background to the onset of the tumor process, making intestinal cells susceptible to tumor progression and promotion through the accumulation of further mutations as a result of epigenetic phenomena largely

FAP offers an ideal model for the study of CRC since in these patients "normal" mucosa coexists with low and high-grade dysplastic lesions as well adenocarcinoma, i.e. all the stages of the carcinogenetic process. For this reason the modifications occurring during the

Phytoestrogens (heterocyclic non steroid phenols) are plant-derived compounds with a structural and functional action as estrogen agonists in mammals. To understand their

carcinogenetic process are easily comparable and free from individual variations (4).

and the possible role of these latter substances in the prevention of colon cancer.

proceeds down the adenoma–carcinoma sequence pathway (2).

**1. Introduction** 

**2. APC gene in colorectal cancer** 

influenced by environmental factors (3).

**3. Estrogens in colorectal cancer** 

