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.