Dietary polyunsaturated fatty acids and colorectal neoplasia

Epidemiology has implicated dietary fat in mortality associated with some of the most common forms of cancer, including those affecting the intestinal tract, breast and prostate. Polyunsaturated fatty acids, and arachidonate in particular, have been unequivocally linked to experimental colorectal carcinogenesis. Dietary, pharmacologic and genetic manipulation of tissue arachidonic acid and its conversion to bioactive lipids has provided insights into pathogenic mechanisms as well as compelling evidence to support rational preventative and therapeutic methods of disease intervention. While it is clear that conversion of arachidonate to prostaglandins and other bioactive lipids contributes significantly to tumorigenesis in the intestinal tract and other organs, it is also clear that no single metabolic pathway or lipid in this complex biochemical network is solely responsible for dietary or pharmacologic benefits evident in epidemiologic studies. We will review some of these data and provide a summary of our own work showing that conversion of arachidonate to prostaglandin E2 contributes significantly to tumor growth through the modulation of apoptosis and cellular proliferation.