Integrated Epidemiologic Study of Ultra-processed Foods and Colorectal Cancer Survival

PROJECT SUMMARY/ABSTRACT Colorectal cancer (CRC) remains a leading cause of cancer deaths in the US and is one of the cancers most strongly associated with a suboptimal diet. Within various dietary components, ultra-processed foods (UPFs) are emerging as an increasingly important risk factor for CRC. UPFs make up nearly 60% of Americans' daily

calories. A high UPF intake may increase CRC risk or worsen its prognosis through altered metabolites that may impact glycemic or inflammatory responses, or tumor microenvironment, resulting in cancer progression. Food processing may also introduce carcinogens and certain UPF components can contribute to somatic mutations.

Besides, a high UPF intake is associated with excess intake of calories, leading to adiposity, an established risk factor for CRC. Thus, UPFs could be an important dietary risk factor for CRC progression and yet the UPF-CRC survival has not been adequately studied. While evidence suggests that CRC progression is associated with

metabolites modulated by diet, the metabolomic profiles associated with UPFs remain to be characterized. Constituents of UPFs such as red or processed meats have been related to alkylating DNA damage and increased CRC mortality, yet the role of UPFs remains unclear. These unknowns highlight the critical need to

comprehend the association between UPFs and CRC survival and the molecular determinants of this relationship for improving long-term CRC survivorship. Well-established large prospective cohort studies are crucial to offering rigorous data to elucidate the diet-disease association and infer causality. Advances in high-throughput

metabolomic profiling and whole-exome sequencing (WES) show great promise to identify sensitive biomarkers that could better predict the diet-disease relationships. The overarching research goal of this F99/K00 proposal is to investigate the role of UPFs in CRC survival by integrating high throughput -omics and detailed dietary data

collected among men and women from large cohorts. The F99 phase will focus on investigating the association between UPF intake and deaths due to CRC and all causes among CRC survivors (Aim 1); the K00 phase will shift the focus to investigating the molecular correlates of UPF-CRC survival relationship by integrating

metabolomics profiling and tumor WES data and exploring the feasibility of a pilot intervention to reduce UPF intake among CRC patients (Aim 2). The research findings will inform dietary recommendations for CRC survivors, accelerate the discovery of novel biomarkers to pave the way for precision nutrition in oncology care,

and provide new insights into nutrition interventions for improving the long-term survivorship of CRC. Under the mentorship of sponsors at Tufts Friedman School of Nutrition Science and Policy and Harvard T.H. Chan School of Public Health, the candidate will acquire rigorous research training and professional and career development

skills for transition to an independent research career focus on studying the role of nutrition in cancer control and translate evidence into effective nutrition interventions and clinical practices to improve cancer survivorship.