Immune modulation and cancer resistance: Enhancement by ω-3 fatty acids

Abstract

The incidence of cancer of the colon and breast has been steadily increasing in Western countries. The etiology of colon and breast cancer is complex, involving both genetic and environmental factors, including diet. Epidemiological and experimental studies have linked a high dietary intake of ω-6 polyunsaturated fatty acids (PUFAs) such as linoleic acid (C18:2, LA) to an increased risk of cancers of the breast and colon, especially in association with a low intake of ω-3 PUFAs such as docosahexaenoic acid (C22:6, DHA) or eicosapentaenoic acid (EPA) acid. Changes in anticancer immune defenses resulting from this dietary shift in PUFA balance may facilitate cancer progression. Altering the ω-6:ω-3 ratio has been demonstrated to influence immune function in other diseases, however less is known about their effect on immune surveillance during cancer. The biochemical mechanisms whereby decreases in the ω-6:ω-3 ratio of the diet (via increasing DHA and EPA intake) modulate immune function and inhibit tumor growth are not well established but mechanistic studies suggest that this may occur at several sites in the cell. In immune cells, this includes ω-3 PUFA competitively inhibiting arachidonic acid metabolism, altering membrane composition, modifying cell signaling processes and/or changing the expression of genes. In this chapter, we will review the role of the immune system in cancer prevention and promotion, with a focus on evidence from animal and human studies that implicates changes in the level of ω-6 and ω-3 fatty acids in the diet on immune protection from breast and colon cancer. Evidence that points to possible immune mechanisms will also be discussed. Although at the present time it is too early to make any clear recommendations regarding the precise ratio of ω-6:ω-3 PUFA in the diet to impact favorably on anti-cancer defenses, the available evidence presented in this chapter should encourage public health authorities to consider designing primary prevention campaigns to reduce the ω-6/ω-3 ratio of the Western diet by promoting increases in ω-3 PUFA consumption in the population. © 2008 Humana Press Inc.