Maternal diet may influence development of the offspring and may influence future cancer risk. Maternal consumption of diet high in n-6 (omega 6) polyunsaturated fats has been shown to increase risk for mammary gland cancer (Hilakivi-Clarke et al, 1997). We wanted to know if the substitution of corn oil with canola oil in the maternal diet might reduce the risk for breast cancer. Such a change would decrease dietary n-6 fat and increase n-3 fat. A study was devised to determine whether exposure to a diet that has less omega 6 and more omega 3 FAs during gestation and lactation would reduce the risk for mammary cancer in female offspring. Female SV 129 mice were divided into two groups and placed on diets either containing 10% w/w corn oil (corn oil is 50% omega 6 and < 0.5% omega 3) or 10% w/w canola oil (canola oil is 20% omega 6 and 10% omega 3). After two weeks the females were bred with homozygous C31 Tag transgenic male mice. The transgenic mice bear a transgene for the SV40 large T antigen with a prostatic steroid binding protein promoter. The female progeny, hemizygous for the transgene, are the experimental mice for this study. On a standard diet, females would be expected to develop mammary gland cancer by 6 months of age. At weaning, female progeny from each litter were all maintained on the basal corn oil containing diet. The female hemizygous mice were euthanized at 3weeks, 110, 130, 150 and 170 days. Results showed that the total tumor weight, number of glands with tumor and fraction of mice with tumors were higher in progeny of mother fed a corn oil diet than in progeny of mother fed a canola oil diet. No significant difference in the body weight of progeny from corn oil and canola fed mothers. At weaning the lipid composition of the inguinal fat pad, mammary gland and liver shows a higher level of omega 3 fatty acids in the offspring of mice fed the high n-3 diet. Mammary gland gene expression assay performed on three weeks and 130 days old mice reveals up as well as down regulation in several genes in canola versus corn group. The up regulated genes include CCAAT-enhancer binding protein beta (CEBPβ), a transcription factor that is involved in mammary gland differentiation (550-fold at 130days) and Early growth response 1 (Egr1), a tumor suppressor gene (13-fold at 130days). Genes down regulated include Bcl2-like 1(Bcl2l1), an antiapoptotic gene (-2.03-fold at 3weeks) and Fatty acid synthase (Fas), an enzyme involved in fatty acid synthesis and active in cancer cells (-7.09 at 130days). Western blot analysis confirmed the differential gene expression of CEBPβ and Fas.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B2.
Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC