African Americans suffer disparities in risk of gastrointestinal cancers, which are etiologically linked with inflammation. Dietary and other behavioral factors, rather than genetic, likely play a dominant role in explaining the disparity, as incidence of gastrointestinal cancers is much lower in rural Africans. Vegetarians in the Adventist Health Study-2 (AHS-2) cohort were found to have decreased risk for colorectal and gastrointestinal cancers relative to omnivores. Additionally, vegetarians have lower concentrations of inflammatory cytokines, and higher levels of anti-inflammatory bioactive compounds. Thus, habitual vegetarian and omnivorous dietary patterns may differentially regulate inflammation. However, there is a need for identification of other diet- related metabolites and molecular processes that influence inflammation and consequently cancer. The metabolome and DNA methylome are profoundly altered in cancer and also impacted by select foods or dietary conditions. However, it is unclear how they are influenced by dietary patterns characterized by consumption of plant- or animal-based foods. African Americans, who tend to have poorer nutrient profiles and dietary behaviors, have different metabolic and epigenetic signatures from Caucasians. Thus, these differences could be partly explained by diet. Secondary polyphenol and other plant-derived metabolites may prevent inflammation, while oxidative and energy-related metabolites that accumulate with consumption of animal-based foods may promote chronic inflammation. These different metabolite profiles may be characterized by opposing global or gene-specific alterations in methylation that influence genome stability and expression of cancer-relevant genes. Methyl-donating metabolites (folate, choline, and methionine) associated with a wide variety of foods influence cancer, but findings have not been consistent. It is plausible that the precise methylation activity of methyl donor and other metabolites is largely dependent on inflammatory status, which itself has been found to regulate methylation, and is defined by dietary pattern. Using blood samples from vegetarians and omnivores in the AHS-2 cohort, specific aims will examine the independent influences of dietary pattern and race on plasma metabolites and gene methylation, and determine if the effect of dietary patterns on these biomarker profiles is different in African Americans relative to Caucasians. In addition, correlations between a priori candidate, diet-associated metabolites and genes relevant to inflammation and cancer will be examined. The proposed project will provide new training in molecular epidemiology, genomics, and health disparities research. Activities for training include workshops, conferences, short courses, and seminars, along with grant writing classes and working groups. Research will be facilitated by the expertise of mentors experienced in experimental nutrition and metabolomics, statistical methodology and epidemiology, and cancer biology and health disparities, in conjunction with collaborating scientists with additional expertise in bioinformatics and epigenetics.

Public Health Relevance

Dietary patterns impact the metabolome and consequently inflammation, possibly regulating cancer development through alterations in the DNA methylome. This research will examine the independent and combined influences of dietary pattern (vegetarian vs omnivorous) and race on metabolic and epigenetic alterations, and subsequently, metabolite-methylation associations among healthy participants of the Adventist Health Study-2 cohort. This study will elucidate the role of dietary patterns in cancer disparities, and ultimately foster the development of effective interventions for cancer prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01MD015194-01A1
Application #
9977535
Study Section
Special Emphasis Panel (ZMD1)
Program Officer
Das, Rina
Project Start
2020-09-25
Project End
2023-04-30
Budget Start
2020-09-25
Budget End
2021-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Loma Linda University
Department
Type
Schools of Public Health
DUNS #
009656273
City
Loma Linda
State
CA
Country
United States
Zip Code
92350