Unprecedented Use of DNA Modeling to Identify Lifetime Risk for Colon Cancer

Principal Investigator: Mohammad Ali Abbass, MD, Assistant Professor of Surgery (Gastrointestinal), Northwestern University Feinberg School of Medicine Colorectal cancer is the second most common cause of cancer-related death in the United States, but it is also largely preventable with screening. The Abbass team is identifying a genetic tool based on blood samples that can accurately predict an individual’s lifetime risk for developing colorectal cancer. The researchers will use DNA extracted from blood specimens of Northwestern Medicine patients who have either been diagnosed or confirmed clear of colorectal cancer. They will then evaluate changes that occur in the DNA building blocks to validate a polygenic risk score established for European patients. The aim is to use this score to identify patients who lack a family history for colorectal cancer but who should potentially begin their colorectal cancer screening before age 45, the age currently recommended to begin screening. The project could lead to a larger scale study that would target a more expansive population to initiate earlier screening in selected patients and decrease colorectal cancer-related deaths in younger patients. As a result, many people could more accurately know their individual genetic risk, pursue earlier screening if indicated, and detect colorectal cancer earlier, improving their chances of...

How immune cells promote tissue injury to increase risk of colon cancer

Immune cells called neutrophils protect our body against invading pathogens, but when they accumulate in tissue, they can also cause recurring injury to cells of the gastrointestinal tract. The resulting chronic inflammation in the colon is a hallmark of inflammatory bowel diseases (IBDs). It is also a well-recognized risk factor for the development of colorectal cancer. Dr. Sumagin’s preliminary findings suggest that neutrophils may influence the transformation of normal cells into cancerous ones by increasing the occurrence of mutations, inhibiting the ability of cells to repair themselves and ultimately promoting cancer development. The team is focusing on specific mutations in the tumor suppressor gene TP53—the most frequently mutated gene in Colitis-associated colon cancer. The goal of this project will be to determine whether immune cell-mediated inflammation results in specific mutations in TP53 and to identify these mutations. If successful, this study will open the door to future prognostic biomarkers of inflammation-induced colorectal cancer. Funding will partially support the research personnel involved in this work and for purchases of essential reagents needed to complete these...

How Does Inflammation Increase the Risk of Cancer in Intestinal Tissues?

Normally immune cells like polymorphonuclear neutrophils (PMNs) protect our body against invading pathogens, but sometimes they go overboard. Accumulating in tissue they can cause cell injury in the GI tract, leading to the development of Inflammatory Bowel Diseases (IBD) and potentially, colorectal cancer. While neutrophils can drive inflammation, it remains unclear just how they contribute to tumor development. Supported by funding from a Digestive Health Foundation, Ronen Sumagin, PhD, a faculty member in the Department of Pathology at Northwestern Medicine and colleagues plan to define the mechanism that allows neutrophils to both promote abnormal cell mutations and inhibit DNA repair genes. They will also study if neutralizing these harmful effects can prevent increased mutations and cancer. The research team will specifically explore the potential use of targeted inhibition PMN-derived miRNAs as an antitumor therapy and test the theory that PMNs play a critical role in causing genomic instability, cellular transformation and tumor growth. Recurring PMN-mediated injury to the intestinal lining is a hallmark of IBD and significantly enhances the risk of developing colorectal cancer (CRC). Current IBD therapies include steroids, which have harsh long-term side effects. Confirmation of the role of PMNs, and identification of specific targets to inhibit PMN activity in patients with IBD, could help reduce the need for steroids and lead to the development of future diagnostics for colon cancer. Preventative treatment in this vulnerable patient population—many of them young adults—could significantly reduce their risk of colon cancer, which typically increases with age. Beyond IBD patients, Dr. Sumagin’s groundbreaking discovery of the relationship between inflammation and cancer could have far-reaching implications for all inflammatory-related cancers, from...

Developing Video-Based Education to Improve Patient Completion of Colorectal Cancer Screening

Screening colonoscopies have been credited with turning the tide against colorectal cancer—the second leading cause of death in the United States—with early prevention and treatment. Yet barriers, from patient fears to cultural influences, keep many Americans from undergoing the potentially lifesaving procedure. Even when screening colonoscopies are scheduled, no shows and cancellations are common. Some 10 percent of Northwestern Medicine’s scheduled patients change their minds at the last minute and never make it to their appointments. Not only do patients miss out on this effective preventive health screening but they also contribute to wasted healthcare resources due to unfilled endoscopy appointments. Patient education remains critical to convincing individuals of the importance of colon cancer screening. In most busy clinical practices, though, healthcare practitioners often can’t devote the necessary time to the topic. Given the constraints of the current patient-primary care provider relationship, novel methods for delivering this vital information are needed to improve screening rates across the nation. Patient portals have fast become a standard feature of many electronic health records (EHRs) systems.  Allowing patients to schedule appointments, access test results and communicate with their doctors, EHRs can present an alternative channel for patient education materials. Northwestern Medicine investigators have already shown that the use of patient portals for educating patients on the importance of pneumonia vaccinations works. Patients who viewed a video on the subject were significantly more likely, than those who didn’t, to agree to being vaccinated. Thanks to a grant from the Digestive Health Foundation, researchers led by Rajesh N. Keswani, MD, Director of Quality for the Digestive Health Center, will apply the novel patient portal...