The Role of Mismatch Repair and Microbiome in Inflammation-Associated Colon Cancer
Abstract
Colorectal cancer represents the third most common cancer type worldwide and is the second leading cause for cancer-related mortality in the United States. Colorectal cancer risk factors include genetic, environmental, and genotoxic factors, unbalanced fat-rich diet, and sedentary lifestyle. In addition, pathogenic gut bacteria have been proposed as a strong modulator of colorectal cancer development. The DNA mismatch repair system is essential for maintaining the integrity of mammalian genomes, and defects in mismatch repair are the cause of the cancer syndrome hereditary nonpolyposis colorectal cancer or Lynch syndrome and a significant number of sporadic cancers in humans. It has been shown that an inefficient DNA mismatch repair system is a strong predisposing factor for the development of colorectal cancer; therefore, creation of animal models with the same primed genetic background is an extremely powerful tool. These models will allow me to dissect the critical processes underlying colorectal cancer development to find vulnerabilities that can be employed in the design of novel and more effective avenues for colorectal cancer treatment. Moreover, I proposed to investigate the role of gut bacteria as a possible modulator of colorectal cancer with the potential to discover global changes in the colonic bacteria associated with tumor development. This aspect of my project can offer the possibilities to design experiments to test more efficient colorectal screening and preventive approaches. This award will allow me to expand our understanding of pathways that modulate colorectal cancer development with the ultimate goal of advance our horizon in designing more efficient therapeutic treatment. Overall, this study is intended to advance the basic knowledge of colorectal cancer development and cancer patient treatment to benefit active duty Service members who show a high rate of colorectal cancer incidence and might be exposed differently to colorectal cancer risk factors.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610215
Entities
People
- Elena Tosti
Organizations
- Albert Einstein College of Medicine
- United States Army