Project Number: 1950-51000-064-05
Project Type: Specific Cooperative Agreement

Start Date: Oct 01, 2006
End Date: Sep 30, 2011

Objective:
LAB:Vitamins and Carcinogenesis To determine the complex roles the 'one-carbon nutrients', (methionine, choline and the B-vitamins, folate, B12, B6, and B2), as well as components of the diet that are one-carbon antagonists (such as alcohol) play in modifying metabolic and genetic pathways that lead to human cancer. To define how the mechanistic knowledge acquired through objective #1 should be used to modify dietary habits, nutritional supplementation, and other nutritional interventions in order to prevent cancer. New advances made by this laboratory can thus be translated into public health initiatives that effectively reduce the burden of cancer in our society. To define the biochemical, molecular and pathophysiologic processes that underlie the apparent effects of vitamin D and calcium in the modulation of cancer development, and to examine how genetic background and environmental factors further impact these effects.

Approach:
LAB:Vitamins and Carcinogenesis Mechanistic questions will largely be examined in studies utilizing cell cultures and animal models. We have several cell lines derived from normal human colonic epithelial cells. The availability of one-carbon nutrients for these cells can easily be manipulated to examine the consequences of limited, or supplemental levels of nutrient availability. A variety of mouse models will also be used to examine the consequences of limited nutrient availability, including genetically engineered animals who either have a predisposition towards colon cancer or a polymorphism in a folate-dependent enzyme. Studies conducted in human volunteers, in which they undergo folate depletion for several weeks, will also be used to examine mechanistic questions, whereas intervention trials, where people at enhanced risk of colon cancer are randomly chosen to receive folate or placebo, will be used to translate this mechanistic work into answers regarding the possible utility of folate in the prevention of cancer.