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Genetic testing ‘one of our best approaches’ for fighting colon cancer
ORLANDO — Knowing who to test, when to test and the implications of genetic testing give gastroenterologists the opportunity to proactively manage their patients with colorectal cancer, according to one expert at the GI Pathophysiology Course preceding the World Congress of Gastroenterology at ACG 2017.
“The key point to making these strategies of universal screening of colorectal cancer cases for the possibility of genetic syndromes rests in being able to test other relatives before their cancer diagnoses in order to identify individuals who need early intervention and prevent cancers,” Elena M. Stoffel, MD, MPH, director of the Cancer Genetics Clinic at the University of Michigan, said during her presentation. “The cost of genetic testing strategies on a population basis drops significantly once there are at least three relatives tested per germline mutation identified.”
She noted that the polyposis syndromes that gastrointestinal endoscopists are most used to identifying remain in the minority of hereditary cancer syndromes in CRC. Instead syndromes like Lynch are more common, with Lynch being estimated at one in 280 people in the general population being carriers.
Stoffel explained that although historical rates suggest a 5% prevalence of germline mutations in CRC, more recent studies saw a 10% occurrence and the epidemic of early-onset CRC shows that one in five people diagnosed with CRC at age 50 or younger has a germline mutation.
Molecular profiling
“Universal screening of all colorectal cancers for mismatch repair deficiency is warranted,” Stoffel said. “All colon cancers are not created equal.”
She said 15% of CRCs show hypermutated phenotypes and some do not overlap with microsatellite instability.
“This cohort of hypermutated colorectal cancers showed different mutation profiles and different clinical outcomes than the non-hypermutated colorectal cancers,” Stoffel said. “New immunotherapies can be very helpful in treating patients with microsatellite unstable cancers who have failed conventional therapies.”
Molecular profiling can predict immune response and therapy response so all CRC should be screened for mismatch repair deficiency phenotypes and somatic mutations in KRAS, BRAF and NRAS, she said.
Between 50% and 80% of non-invasive neoplasms will be able to produce mismatch repair deficiencies and could help lead to diagnoses like Lynch, Stoffel added.
Further genetic testing
When germline mutations such as Lynch are found, it can greatly influence the management of the patient diagnosed, but also his or her family.
The following should be sent for genetic testing:
- patients with suspicious family history based on Amsterdam and Bethesda guidelines as well as those with a Premm model score greater than 5%;
- those with mismatch repair deficient CRCs without somatic BRAF mutations;
- patients with three or more gastrointestinal hematomas;
- diagnosis under age 50; and
- patients with 20 or more colorectal adenomas.
When found, a patient is eligible for increased screenings for colon cancer as well as prophylactic measures for other cancers such as uterine cancer.
“Germline and tumor molecular profiles can guide management, can guide not only the choice of chemotherapy but also the surveillance intervals for colorectal cancers as well as screening recommendations for extracolonic cancers. Finally, identification of individuals at increased risk for colorectal cancers is one of our best approaches for fighting this disease,” Stoffel said. – by Katrina Altersitz
Reference: Stoffel E. GI Pathophysiology Course. Presented at: World Congress of Gastroenterology at American College of Gastroenterology Annual Scientific Meeting; Oct. 13-18, 2017; Orlando, FL.
Disclosures: Stoffel reports no relevant financial disclosures.