6 Things to Know About Genetics in GI Cancers
As genetic testing is fast becoming a defining aspect of cancer care prevention, treatment, and recurrence monitoring, its role is becoming more apparent in gastroenterology, according to N. Jewel Samadder, MD, MSc, a professor of medicine at Mayo Clinic Arizona, in Phoenix.
Approximately 10% to 15% of colorectal cancers are clearly hereditary, with mutations in single genes that predispose a person to the development of these cancers. Important monogenic CRC syndromes include Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, and the rare hamartomatous polyposis syndromes. Another 20% are associated with a strong family history of CRC but no single genetic cause and the remaining 65% are sporadic and likely “a combination of genetic elements plus environment and bad luck,” Dr. Samadder said. In a presentation at ACG 2024, Dr. Samadder discussed areas of genetic testing that are important for GI clinicians to be aware of, so they can help identify these mutations and enhance the prevention and treatment of inherited cancers.
Forms of Genomic Testing
Germline sequencing examines hundreds (or thousands) of genes in a single sample of blood or saliva and identifies inherited genetic disposition for diseases, Dr. Samadder explained. Since a history of cancer in a first- or second-degree relative is an important determinant of inherited risk, such genetic testing should be accompanied by a conventional family history assessment covering three generations in detail.
A second form, somatic testing, identifies genetic features within tumors that can guide the use of targeted therapy. A third method involves the measurement of circulating tumor DNA to detect minimal residual disease after treatment, which can signal disease recurrence and is also the backbone of the new multi-cancer detection (MCD) tests.
Defining Hereditary Cancer Risk
The determination of hereditary cancer risk for a given patient takes into account family history, tumor phenotype, and the expression of mismatch repair (MMR) proteins by immunohistochemistry. “In today’s world, we don’t test patients for one, two or even half a dozen cancer genes at a time. We do multigene testing where we look for up to 100 different cancer-related genes, covering all the major cancers on a single panel using a single sample of blood or saliva,” Dr. Samadder said. “Multigene panel testing is becoming the standard for patients with early-onset GI cancers.”
Once the proband with an inherited cancer is identified, cascade testing is offered to family members, he said. This is commonly done via single-site genetic testing that zeroes in on the newly identified familial variant. Patients with this gene can then take preventive measures.
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