Dietary Polyunsaturated Fatty Acids and Tumorigenesis

Western style diets characterized by high intakes of energy, fat, meat, refined grains, and sugar combined with low intakes of fiber, calcium, and fruits and vegetables have been strongly linked to an increased risk of colorectal can-cer.261 62 Similar correlations have been observed in animal models with Apc gene defects. Increasing beef and fat content positively affects intestinal tumor load and some dietary fibers appear to be protective.63-66 The feeding of a Western style diet has been shown to increase intestinal tumorigenesis in the Apc1638 mouse model67 and enhance hyperproliferation of epithelial cells (in various tissues) in null mice (wild type for Apc).68 69

Among the components of the diet, the amount and type of dietary fat consumed is of particular importance.170-72 Certainly, a number of PUFAs have proved to be very promising as antitumorigenic lipids in both chemically induced tumor models and models containing germline mutations.73-77 In an effort to systematically evaluate the efficacy of a variety of dietary PUFAs on intestinal tumorigenesis in vivo, we fed ApcMin/+ mice selectively tailored diets containing individual fatty acid ethyl esters (1.5 to 3%, w/w). The strength of this dietary design allowed us to directly compare different fatty acids from different families.78 The fatty acids evaluated included GLA and AA from the n-6 family, ALA, SDA, EPA and DHA from the n-3 family, and conjugated linoleic acid (CLA). CLA refers collectively to a number of positional and geometric isomers of LA whose double bonds are in conjugation (typically in the 9 and 11 or 10 and 12 positions).20

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