It is becoming recognized that an emphasis on the prevention of breast cancer is needed to reduce breast cancer morbidity and mortality. The results of epidemiology studies indicate that diet has a profound influence on breast cancer risk. The long term objectives of this research are to identify dietary changes that humans might make to reduce the risk for breast cancer and to identify biomarkers that might indicate that risk for breast cancer has been reduced. One feasible change may be by altering the type of fat consumed in the diet. Consumption of omega 3 fatty acids (FAs) is usually associated with a lower incidence of breast cancer whereas exposure to high omega 6 fatty acids during gestation and lactation has been shown to increase the future incidence of mammary cancer in mice. We hypothesize that when compared to a diet with a low ratio of n-3/n-6 (high n-6 diet) FAs, maternal consumption of a diet with a high ratio of n-3/n-6 FAs (high n-3 diet) during gestation and lactation of the offspring will reduce the risk for mammary cancer in female offspring via alteration in exposure of the offspring to lower prostaglandin ?2 and estrogen during early development of the mammary gland. A transgenic mouse model that is expected to develop mammary gland cancer by 6 months of age will be used in this study. We will assess whether exposure to modest amounts of omega 3 fatty acids during gestation and lactation and/or throughout life can delay or prevent the occurrence of mammary cancer. Breeding females will be fed one of two diets containing either a high percentage of omega 6 or a high percentage of omega 3 fatty acids and to modification of PGE2. At weaning, female offspring will be randomized to the two diets and followed for mammary cancer development. Tumorigenesis will be assessed up to eight months of age by morphological analyses. Mice will be euthanized at one month intervals to track the development of cancer in the mammary glands and for biochemical analyses. At weaning and at 4 months of age, gene expression in the mammary glands will be assessed by microarray analyses. This will allow us to determine whether expression of genes important to breast cancer development is altered by the omega 3 diet in a manner that would indicate reduction in risk for mammary gland cancer. These changes may make useful biomarkers for future clinical trials. Normal mice will also be exposed to omega 3 fatty acids to ascertain that the observed effects can occur in normal animals and are not due to some unknown interaction between the transgene and the diet. The results from this study: 1) will allow us to determine if omega 3 fatty acids can delay mammary cancer in this mouse model, 2) will demonstrate the effect of exposure to omega 3 fatty acids during gestation and lactation, 3) may identify putative biomarkers of risk that will be useful for future human breast cancer prevention studies and 4) could lead to human dietary recommendations for reduction in risk for breast cancer. ? ? ?
