differentiation, and apoptosis) in order to begin to establish linkages between epigenetics, methylation patterns, and tumor incidences/behaviors. NIAAA is specifically interested in receiving applications that examine the impact(s) of chronic alcohol consumption on levels of SAM, betaine, and folate, and possible associations with DNA methylation and cancer. NIDDK is particularly interested in receiving applications that address normal and neoplastic conditions focusing on the impact of epigenetics on cell division, differentiation, and/or apoptosis in the gastrointestinal (GI) tract and related organs. -This FOA utilizes the NIH exploratory/developmental (R21) grant mechanism and runs in parallel with two other FOAs of identical scientific scope, one being PA-06-414, which solicits applications using the NIH Small Grant (R03) award mechanism, and the other being PA-06-412 which solicits applications using the NIH Research Project Grant (R01) award mechanism. -Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications; therefore, the anticipated number of awards is not known. -Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received. -The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Direct costs are limited to $275,000 over an R21 2-year period, with no more than $200,000 in direct costs allowed in any single year (note that consortium [third party] facilities and administrative costs are not included in the direct cost limitation). -Eligible organizations include: for-profit organizations; non-profit organizations; public or private institutions, such as universities, colleges, hospitals and laboratories; units of State and local governments; eligible agencies of the Federal government; domestic or foreign institutions/organizations; faith-based or community-based organizations; Indian/Native American Tribal Governments (Federally Recognized); Indian/Native American Tribal Governments (Other than Federally Recognized); and Indian/Native American Tribally Designated Organizations. -Eligible Project Directors/Principal Investigators (PDs/PIs) include any individual from the institution with the skills, knowledge, and resources necessary to carry out the proposed research. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. -Applicants may submit more than one application, provided each application is scientifically distinct.