COLON-MD: Colon Cancer Longitudinal Study of the Microbial and Dietary Factors That Influence Response to Treatment
Abstract
Alarmingly, incidence and mortality from colon cancer have risen 51% among those between the ages of 20-49 since 1994, which is the age of the vast majority of the military population (SEER). Moreover, 45% of those diagnosed with colorectal cancer have a child under the age of 10 at the time of diagnosis (Colorectal Cancer Alliance Survey, 2017). Greater than 50% of all patients receiving chemotherapy for treatment of colorectal cancer report diarrhea, with over 10% reporting severe diarrhea that is both dose-reducing and can be life threatening. Short-term side effects include significant weight loss, stopping treatment, and reduction in quality of life. Long-term, chronic diarrhea, muscle wasting, and weight loss are common side effects of colon cancer treatment. However, no method of prediction exists for determining which individuals will have the worst side effects. One possible way to predict patients at risk for chemotherapy-induced diarrhea is using the composition of gut microbiome, the collection of microbes that live in the gastrointestinal tract taken prior to treatment. This same approach has been extremely successful in predicting cancer patients who respond to other types of anti-cancer therapy (i.e., immunotherapy). Studies show that (1) changes in the gut microbiome and diet are associated with CID, (2) the gut microbiome from patients with melanoma is able to predict severe colon inflammation, and (3) three separate studies in colon cancer demonstrate that CID resulting from radiotherapy could be predicted by the gut microbiome (stool samples) taken prior to treatment. However, since there have been no long-term studies that collected stool and dietary information prior to, during, and after chemotherapy, we do not know the precise dietary and microbial factors to could allow us to predict CID or develop treatment options. The gap in knowledge this proposal seeks to fill is identification of dietary and microbial changes associated with CID incidence and severity during colon cancer treatment. The goal of this proposal is to identify biomarkers from gut microbiota and diet that can predict CID by recruiting patients diagnosed with colon cancer. My overarching career objective is to conduct research that generates biomarkers and provides mechanistic insight for prevention, treatment, and increased quality of life in patients with colon cancer. I have constructed a training plan and mentorship team to achieve these research and career goals, which include: (1) long-term assessment of dietary and microbial factors changes during chemotherapy, and (2) advanced metabolic pathway analysis. This training experience will be guided by an expert mentorship team who are leaders in their respective fields of colon cancer pathogenesis, biochemistry, and metagenomics. My short-term research goals focus on identifying dietary and microbial predictors of CID. To reach these goals, I will combine two powerful tools pharmacogenomics, which links pharmacology, toxicology and genomics, and the immune system to not only stratify patients by CID risk but also to identify cellular mechanisms that can be targeted to prevent CID. The proposed research aims to test the hypothesis that the microbiome at baseline, prior to colon cancer treatment, and dietary intake/malnutrition can predict CID. Participants will include patients diagnosed with colon cancer (N=112) that go on to cancer therapy (FOLFOX). They will be requested to provide stool samples prior to and during cancer treatment, as well as providing online 24-hour dietary recalls. The physician will also collect tissue during surgery and blood prior to and during FOLFOX therapy. The multiple collection time-points for both diet and gut microbiota during cancer therapy is essential for the development of CID predictors and for future prevention strategies to reduce incidence and severity of CID. Results from this study will be used to (i) inform the constr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010570
Entities
People
- Leigh Greathouse
Organizations
- Baylor University
- United States Army