The candidate's long-term career goal is to become an independent investigator with interdisciplinary skills and expertise in dietary patterns, epidemiology, biomarkers and metabolomics, with a focus on cancer prevention and control. Several dietary patterns have been associated with colorectal cancer (CRC) risk but underlying mechanisms are not fully understood. Also, evidence is lacking on the consistency of dietary guidelines for overall health and CRC prevention given that it is not feasible to have an optimal diet for every disease. Furthermore, other biomarkers of diet, such as metabolomic profiling, have not been assessed with respect to CRC risk. Metabolomics is uniquely suited to assess metabolic responses to dietary stimuli, given that it is situated downstream to all the other ?omics?. Building on his prior work in hypothesis-driven dietary patterns and CRC prevention, the candidate seeks to fill these knowledge gaps by proposing to: 1) use a standardized methodology to compare the best diet for overall health with the best diet for CRC prevention, and further determine if any associations of dietary patterns with CRC prevention are mediated by mechanisms involving inflammation and insulin; 2) determine the inflammatory metabolome that intersects pathways due to inflammatory diets and circulating inflammatory markers, and evaluate the association of this unique metabolome with CRC risk; 3) determine the insulinemic metabolome that intersects pathways due to insulinemic diets and circulating insulin markers, and evaluate the association of the unique metabolome with CRC risk. To achieve these goals, the candidate and his mentors have designed a career development plan for research and educational training to: 1) help him develop expertise in dietary patterns research methods; 2) acquire skills in mediation analyses and 3) integrate and synthesize data from multiple sources including epidemiological, nutritional, and biological data. To achieve the proposed research aims, the candidate will utilize two large prospective cohort studies, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), in which dietary and nondietary data have been collected every 2 to 4 years among 173,230 women and men over the last ?30 years, with ?3,400 CRC cases and ?43,800 all-cause deaths. Within these cohorts, a substantial number of participants donated blood samples that have been used to measure concentrations of several circulating inflammatory and insulin markers, and metabolites. This integrated interrogation of dietary patterns, biomarkers and metabolomics data will identify novel biomarkers for CRC early detection and prevention, and will improve the design of guidelines for healthful lifestyles that are optimized for CRC prevention. The interdisciplinary mentoring team will provide the requisite expertise to ensure the successful implementation of this K99/R00 proposal and the candidate's smooth transition to an independent investigator.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in American men and women with ?130,000 new cases each year. Several dietary patterns have been associated with CRC risk but underlying mechanisms are not fully understood. We thus propose to integrate dietary patterns, biomarker and metabolomics data to comprehensively investigate biological pathways linking dietary patterns and CRC risk, which will lead to the identification of novel biomarkers for CRC prevention and early detection.
|Wirth, Janine; Song, Mingyang; Fung, Teresa T et al. (2018) Diet-quality scores and the risk of symptomatic gallstone disease: a prospective cohort study of male US health professionals. Int J Epidemiol 47:1938-1946|
|Liu, Li; Tabung, Fred K; Zhang, Xuehong et al. (2018) Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum. Clin Gastroenterol Hepatol 16:1622-1631.e3|
|Sparks, Jeffrey A; Barbhaiya, Medha; Tedeschi, Sara K et al. (2018) Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women. Clin Rheumatol :|
|Tabung, Fred K; Liu, Li; Wang, Weike et al. (2018) Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men and Women. JAMA Oncol 4:366-373|
|Tabung, Fred K; Wang, Weike; Fung, Teresa T et al. (2018) Association of dietary insulinemic potential and colorectal cancer risk in men and women. Am J Clin Nutr 108:363-370|
|Zheng, Jiali; Tabung, Fred K; Zhang, Jiajia et al. (2018) Association between Post-Cancer Diagnosis Dietary Inflammatory Potential and Mortality among Invasive Breast Cancer Survivors in the Women's Health Initiative. Cancer Epidemiol Biomarkers Prev 27:454-463|
|Tabung, Fred K; Giovannucci, Edward L; Giulianini, Franco et al. (2018) An Empirical Dietary Inflammatory Pattern Score Is Associated with Circulating Inflammatory Biomarkers in a Multi-Ethnic Population of Postmenopausal Women in the United States. J Nutr :|
|Petimar, Joshua; Tabung, Fred K; Valeri, Linda et al. (2018) Mediation of Associations Between Adiposity and Colorectal Cancer Risk by Inflammatory and Metabolic Biomarkers. Int J Cancer :|
|Petimar, Joshua; Smith-Warner, Stephanie A; Fung, Teresa T et al. (2018) Recommendation-based dietary indexes and risk of colorectal cancer in the Nurses' Health Study and Health Professionals Follow-up Study. Am J Clin Nutr 108:1092-1103|
|Keum, NaNa; Yuan, Chen; Nishihara, Reiko et al. (2017) Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers. Int J Cancer 140:2648-2656|
Showing the most recent 10 out of 18 publications