The central unifying theme of the program is to secure an understanding of the etiology of the main nutritionally-linked cancers in man, namely, breast, colon, and prostate cancer, as the basis for their prevention. This requires a concerted, multidisciplinary effort involving epidemiologic, metabolic epidemiologic, and experimental laboratory studies. Current concepts in cancer causation suggest that there are genotoxic or initiating agents, and agents such as promoters, acting by epigenetic mechanisms. Application of these concepts to factors responsible for the nutritionally-linked cancers has, thus far, provided evidence that, in part, nutritional factors bear on promotion. The following integrated studies are specifically designed to gain, further insight into the mechanisms whereby dietary factors operate in modifying carcinogenesis. In addition, two experimental approaches are designed to provide leads to the possible genotoxic elements which may be associated with gastric cancer on the one hand, and colon cancer and possibly other nutritionally-linked cancers on the other hand. The first segment aims to test the hypothesis that the risk for colon cancer is associated with specific qualitative and quantitative parameters in fecal bile acid patterns and with fecal mutagens which, in turn, reflect dietary fat and fiber intake. These studies involve determination of the metabolic epidemiology of colon cancer in three human populations with markedly different rates of colon cancer. Extracts of stools from such groups will be studied in organ cultures of rat colon to examine the possibility that differences seen at the population level are reflected in the possible cocarcinogenic or promoting effect in vitro. Since differences in breast cancer incidence around the world linked to nutrition are seen most remarkably in postmenopausal women, comparative metabolic epidemiology studies are proposed with emphasis on hormonal balances in postmenopausal women in populations at different risk. The aim is to establish whether specific hormonal profiles in plasma and breast fluid are linked to diet. Study of the modification of dietary factors, especially fat types and amount will permit delineation of the corresponding hormone changes. A combined experimental study on breast and colon cancer aims to elucidate the mechanisms whereby diet and specific dietary fats enhance tumor development. The effects of qualitative and qua (Text Truncated -Exceeds Capacity)