Increased age limit for genetic testing in CRC identifies more families with Lynch syndrome

Increasing the age limit for routine genetic testing in patients with colorectal cancer could help identify more families affected by Lynch syndrome, the most common inherited colorectal cancer syndrome contributing to about 5% of all colon cancers, according to research shared at the annual conference of the European Society of Human Genetics.

Identifying families that carry a mutation for Lynch syndrome will help to decrease mortality from the disease, which can be reduced by more than 60% over 15 years when appropriate prevention measures are implemented, according to Nicoline Hoogerbrugge, MD, PhD, head of the Radboud University Medical Center Expert Center on Hereditary Cancers in The Netherlands.

“We know that, at present, only between 20% and 30% of people with Lynch syndrome have been identified,” she said in a press release. “Most countries rely on detection through family history and early age at diagnosis, and this leads to significant underdiagnosis. We have shown that, by raising the age limit for testing we are able to detect new affected families who would not have been identified previously.”

To determine whether increasing the age limit from 50 to 70 years for routine mismatch repair (MMR) deficiency testing in CRC resulted in increased detection of Lynch syndrome in the Netherlands, Hoogerbrugge and colleagues used national registry data covering 20% of the Dutch population, to evaluate MMR results from 14 pathology labs in 2016.

Overall, MMR results were available for 2,006, of 2,598 cases of CRC, and among 87 patients with test results that suggested they were at risk for Lynch syndrome, 35 were referred for genetic counseling.

Completed genetic testing in 29 patients confirmed Lynch syndrome mutations in 18. Fourteen of these patients had not previously had the disease detected in their family, and eight were aged between 50 and 70 years and had not complied with prior age- and family history-based referral criteria for genetic testing.

“If we had not studied these older patients, their family predisposition to Lynch syndrome would not have been detected until it was too late,” Hoogerbrugge said in the press release. “In every affected family, we can find an average of three people with Lynch. This is clearly a massive advance in the identification of people at risk.”

Hoogerbrugge added that she and colleagues were surprised “to find so many mutations in Lynch syndrome associated genes with a relatively high risk of developing tumors in patients without a family history of the disease,” which confirms the urgent need to increase in the age limit for MMR testing throughout Europe, “so that every new colorectal cancer patient aged below 70 can benefit from it.”

The age limit has also recently been raised in the U.K., but data showing a benefit are not yet available, she noted. Conversely, “we have been able to provide clear evidence of its advantages in the Netherlands, both for patients and for health services,” she said in the press release.

“It is very important to recognize whether a person suffers from sporadic or familiar cancer, as this identifies family members at risk who can take preventative measures,” Joris Veltman, PhD, director of the Institute of Genetic Medicine at Newcastle University in the U.K., and Chair of the ESHG conference, said in the press release. “For this, genetic tests need to be done in cancer patients. This study shows that we should extend these genetic tests to older colorectal cancer patients of whom a significant number suffer from familiar cancer.” – by Adam Leitenberger

Reference:

Hoogerbrugge N, et al. Abstract C17.6. Presented at: 50th Annual Conference of the European Society of Human Genetics; May 27-30, 2017; Copenhagen.

Disclosures: The project was supported by the Dutch Digestive Foundation with funding from the “Vriendenloterij.”

Editor's note: This article was updated on June 2 with additional data from the study presenter.