ABSTRACT
Colorectal cancer is the second most common malignancy in the Western world including the United Sates. In recent years there is a strong upward trend in colon cancer risk in Japan mainly due to Americanization of Japanese food habits. Several epidemiological studies point to a strong association between nutrient composition of the diet and cancer of the colon. The role of types of dietary fat, especially saturated fats of animal origin, n-6- and n-3-rich polyunsaturated fatty acids (PUFAs) in the etiology of colorectal cancer has become increasingly apparent. Epidemiological studies indicate a positive association between the dietary intake of saturated fat and/or animal fat and colon cancer risk and an inverse relationship between the intake of fish and fish oil rich in n-3 PUFAs and colon cancer development. Although the evidence from case-control studies and international correlational studies is not totally consistent, these inconsistencies may have arisen, at least in part, from methodological limitations. Animal, model studies have unequivocally provided evidence that the colon tumor-promoting effect of dietary fat depends on its fatty acid composition and that high dietary n-3 PUFAs lacks colon tumor-promoting effect, as compared to diets high in n-6 PUFAs or saturated fats. Diets rich in n-3 PUFAs inhibit colon carcinogenesis through the modulation of colonicras-p21, cyclooxygenase-2, and inducible nitric oxide synthase activities and apoptosis. Gene expression analysis using DNA microarrays indicates that n-3 fatty acid, docosahexaenoic acid activates cyclin-dependent kinase inhibitors such as p21, p27, p57 and p19 and inactivates antiapoptotic Bcl-2 family of genes, and prostagland in family of genes. These results suggest that decreasing the intake of n-6 PUFAs and saturated fats and increasing that of n-3 PUFAs, particularly eicosapentaenoic acid and docosahexaenoic acid has the potential to be a major component of colon cancer control.