Abstract
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.
