The Dana-Farber Cancer Institute in Boston, Massachusetts, has opened the Lynch Syndrome Center, with the goal of providing genetic counseling and testing to those at risk for the syndrome as well as delivering a new model of coordinated care. It is the first such center.
It is estimated that roughly 1 in 300 people in the general US population have Lynch syndrome. But it remains a largely unknown genetic disease, and most carriers are either undiagnosed or are diagnosed only after they have developed cancer.
"It may be as common as BRCA 1 and 2, or maybe even a little more common, but estimates show that maybe as many as 95% don't even realize that they have it," said Matt Yurgelun, MD, director of the Lynch Syndrome Center. "That was one of the driving forces to creating this center, dedicated both towards the identification and the management of patients and their families with Lynch syndrome."
Lynch syndrome is an autosomal dominant genetic disorder that is associated with germline mutations in DNA mismatch repair genes. It increases the lifetime risk for colorectal cancer by up to 80%; by comparison, the risk for those who do not have such mutations is 4% to 5%. For endometrial cancer, Lynch syndrome increases the risk by up to 60%, compared to about a 3% risk for those who do not carry the mutations.
Lifetime risks for the other cancers associated with Lynch syndrome are also higher than in the general population. These include cancers of the stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin.
Push for Genetic Testing
"Over the past 10 years or so, there has been more of a push to do testing on the tumor specimens themselves, in the setting of a colorectal cancer diagnosis, to look for microsatellite instability or mismatch repair deficiency, which can be a red flag for Lynch syndrome," Yurgelun told Medscape Medical News. "But it still requires that the treating doctor recognizes that and makes the appropriate referral for genetic testing and that the patient follows through with that."
Alterations in several genes involved in DNA mismatch repair have been linked to Lynch syndrome. They include the genes MLH1, MSH2, MSH6, PMS2, and EPCAM. Some experts have said that tumors with high microsatellite instability (MSI-H) should be tested and that patients be screened for Lynch syndrome, regardless of the type of cancer.
In a study presented last year at the annual meeting of the American Society of Clinical Oncology, almost half of patients with MSI-H and MSI-indeterminate tumors who were identified as having Lynch syndrome had cancer types that had not previously been linked to or were only rarely linked to the syndrome. These include mesothelioma, sarcoma, adrenocortical cancer, melanoma, prostate cancer, and ovarian germ cell cancer. Among these patients, 45% did not meet the criteria for undergoing genetic testing for Lynch syndrome. Those criteria are based on family or personal cancer history.
Another hurdle is that even if appropriate genetic testing is undertaken correctly, the resulting information may not be disseminated through the family. "It's always a shame when we are finding Lynch syndrome after the cancer has been diagnosed," he said, "because most of these cancers are extremely preventable if we know someone has Lynch syndrome."
Lynch syndrome is associated with a wide range of cancers that individuals may need to be screened for, explained Yurgelun, "and there's not a ton of awareness out there. So our goal for the center is to be 'one stop shopping,' if you will, for Lynch syndrome individuals and families who test positive."
The Lynch Syndrome Center will create personalized management plans for patients that will help ensure careful monitoring and management, and individuals can be offered earlier and more frequent cancer screening and surveillance. Preventive surgery may also be an option; such surgery can dramatically reduce a patient's likelihood of developing cancer.
Clinical trials will also be offered to Lynch syndrome patients. Such trials will provide more information about the five associated genes and other potential genetic causes. According to a press release, Dana-Farber physician-scientists are working with colleagues nationwide on initiatives that include specialized pancreatic and prostate cancer screenings for individuals with Lynch syndrome.
Medscape Medical News © 2019
Cite this: Dana-Farber Opens First Center Devoted to Lynch Syndrome - Medscape - Apr 01, 2019.
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