Study summary: The current study investigated the impact of soybean-derived isoflavonoids and omega-3 fatty acids from fish oil on apoptosis, proliferation and estrogen receptor (ER) expression in the colon and mammary glands of laboratory rats. Female rats were fed diets high in omega-3 fatty acids (80 g/kg diet) or soy protein (765 mg/kg diet isoflavones) for two weeks, then sacrificed in advance of removal of their colons and mammary glands. Cell proliferation and apoptosis were assessed and ERα and ERβ expression were measured in colon tissue and mammary glands. Fish oil was found to significantly increase apoptosis and decrease mitosis in both types of tissue. These effects were associated with a decrease in the expression of both ERα and ERβ. Soy was found to have no effect on apoptosis in either tissue, but did reduce mitosis in the colon while increasing it in the mammary gland. The changes in proliferation were associated with contrasting changes in ER expression: fish oil significantly decreased both ERα and ERβ, whereas soy increased ERα and decreased ERβ. The authors conclude that the results may provide a mechanism by which omega-3 acids could reduce cancer risk. The interpretation of the results in relation to soy consumption and breast cancer risk requires further investigation.