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Specific Genetic Signatures Associated With Increased CRC-Risk Adenoma Tumors

SALT LAKE CITY (October 28, 2019) – Patients with four specific genetic signatures, known as single nucleotide polymorphisms (SNPs), had a greater risk of developing precancerous colon polyps called adenomas, new research has found. These benign adenomas could become cancerous.

“We identified genetic signatures that were associated with the development of multiple, precancerous polyps,” said lead author Brian Sullivan, MD, of the VA Cooperative Studies Program Epidemiology Center in Durham, NC, and Duke University. “We also found that individuals with more of these genetic signatures had higher numbers of precancerous polyps.”

Sullivan’s research will be presented at the 2019 Collaborative Group of the Americas (CGA) Annual Meeting being held November 3-5, 2019, in Salt Lake City. Michael Hall, MD, MS, chair of the Department of Clinical Genetics at Fox Chase Cancer Center, is president of the CGA.

Sullivan will receive the Colorectal Cancer Research Scholar Award at the 2019 CGA Annual Meeting. This award honors excellence in translational research focused on the molecular biology of colorectal cancer.

The researchers noted that the current lifetime risk of colorectal cancer (CRC) is 5 percent. Physicians cannot predict who will develop CRC, but the researchers hope their study would help identify those at increased risk.

Sullivan and his team investigated 612 patients from two groups, those with advanced neoplasia (which included those with large adenomas and histologic features that are associated with an increased risk for CRC) and an equal number of control patients without neoplasia. They obtained blood samples and measured how many adenomas patients had over a 10-year period. They used corrected Poisson regression to calculate associations between adenomas and 43 different SNPs already known to be associated with CRC.

The investigators pinpointed four SNPs that caused increased adenoma counts: rs12241008 on gene VTI1A, rs2423279 on gene BMP2/HAO1, rs3184504 on gene SH2B3, and rs961253 on gene FERMT1/BMP2. An increased genetic risk score was also linked to increased adenomas.

Given prior research which suggests that people with higher numbers of precancerous polyps may have a higher chance of developing CRC, these authors believe this work could help inform current CRC screening and genetic testing strategies. Patients who are likely to develop many adenomas may be better candidates for CRC screening and continued follow-up by their gastroenterologist.

“We plan to use genetic information from studies like this to identify and screen high-risk individuals earlier in order to prevent CRC morbidity and mortality,” said Sullivan. The research was supported by the VA Cooperative Studies Program.

About Durham VA Health Services
The Durham VA Health Services Research and Development Service (HSR&D) pursues research that underscores all aspects of VA healthcare: patient care, care delivery, health outcomes, cost, and quality. Our 31 core faculty and over 150 staff members conduct creative, high-quality health services research for the benefit of our nation's Veterans, as well as improve the health and quality of life for all of our nation's people.

The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.
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