Understanding Nutritionally Modifiable Risk Factors for Cancer Prevention/Diet-Genetic Interactions

National Cancer Institute, Frederick MD

Investigators

Abstract

The purpose of this research is to investigate the association of body mass index/obesity and diet to secondary bile acid formation in the gastrointestinal tract and their absorption into the circulation. This information will be useful in creating dietary strategies to reduce cancer risk. This Inter-Agency Agreement will capitalize on the joint expertise of the NCI DCP NSRG and the USDA Beltsville Human Nutrition Research Center’s Food Components and Health Lab to conduct human research related to the potential for diet to reduce cancer risk. Bile acids are important for digestion and absorption of lipids and fat soluble vitamins, but also play additional, more complicated roles in health, including regulation of GI epithelial homeostasis. Primary bile acids can be conjugated in the liver, then are stored in the bile duct and are released into the GI tract after a meal to aid in digestion. About 90% of these bile acids are reabsorbed in the distal ileum, while 10% are transported to the colon and undergo microbial metabolism to secondary bile acids, which are thought to promote colon carcinogenesis. Secondary bile acids have been reported as an underrecognized cause of colon cancer. Obesity is associated with altered bile acid metabolism, and may play a role in the increased colon cancer risk seen in overweight and obese individuals. It has been suggested that obese individuals may have increased concentrations of bile acids in plasma; however, the association between BMI, plasma bile acids, and gut metabolism is not well understood. Blood samples and fecal samples from previous prebiotic dietary intervention studies from adult male and female adults ranging in BMI will undergo bile acid analysis. The USDA has identified a set of blood and fecal samples from their biospecimen bank for the project for a bile acid panel analyses. The USDA will associate the blood concentrations of secondary bile acids with fecal concentrations of bile acids and with BMI. The testing hypothesis is that obese individuals will have increased formation of secondary bile acids in the gastrointestinal tract, resulting in increased concentrations of secondary bile acids in plasma.