Title:
Diet, DNA Methylation and Other Epigenetic Events, and Cancer Prevention (R01, R21, R03) (Program Announcement)

Contact:
Sharon A. Ross, Ph.D., M.P.H.
Nutritional Science Research Group
DCP, NCI, NIH, DHHS
Telephone: (301) 594-7547
E-mail: mailto:rosssha@mail.nih.gov

Objective of Project:

The purpose of this initiative is to invite applications for grants proposing innovative preclinical and clinical research to determine how diet and dietary factors impact epigenetic processes involved with cancer prevention. This initiative builds on the 2002 NCI-issued RFA/PAR entitled “Diet, DNA methylation and other epigenetic events, and cancer prevention;” as a result of this earlier initiative, a number of high quality applications were funded and are currently addressing several of the issues that relate to diet and epigenetics in cancer prevention. It is anticipated that this initiative will continue the momentum in this emerging area and encourage collaborations between nutrition and epigenetic experts for the purpose of studying bioactive food components with cancer-preventive activity that may impact epigenetic events.

Description of Project:

Cancer is a manifestation of both abnormal genetic and epigenetic events. Epigenetic events involve mechanisms by which gene function is selectively activated or inactivated. A variety of regulatory proteins including DNA methyltransferases, methyl-CpG binding proteins, histone-modifying enzymes, chromatin remodeling factors, and their multimolecular complexes are involved in the overall epigenetic process. Since epigenetic events are susceptible to change, they represent excellent targets to explain how environmental factors, including diet, may modify cancer risk and tumor behavior. DNA methylation is the covalent addition of a methyl group to the 5 position of cytosine within CpG dinucleotides and it is a fundamental process that not only modulates gene expression, but also is key to regulating chromosomal stability. Abnormal DNA methylation patterns are a hallmark of most cancers, including those of high proportion in the United States, l.g., colon, lung, prostate, and breast cancer. Recent evidence suggests that diet could be a key regulator of DNA methylation and also that DNA methylation may determine the response to bioactive food components.

Very little information currently exists about epigenetics and gene-specific changes in DNA methylation as influenced by bioactive food components, as well as how such changes impact cell vulnerability in cancer development or cell responsiveness to cancer prevention. This initiative is aimed at encouraging innovative research leading to the elucidation of mechanism(s) by which dietary factors influence epigenetic processes as well as increasing our understanding of these processes in cancer prevention. One focus of this concept is to link phenotypic changes to epigenetic alterations induced by specific essential and non-essential nutrients. At this time, very little information exists to adequately evaluate the specificity of individual nutrients, the impact of intakes/exposures, and any acclimation with time and/or tissue specificity. The approach of this initiative is to encourage collaboration between nutrition and epigenetic experts to study bioactive food components with cancer preventative properties, and to e xamine key epigenetic events in cancer processes (l.g., carcinogen metabolism, cell division, differentiation, apoptosis) so that investigators can begin to establish linkages between epigenetic processes, diet, and tumor incidence/behavior.