Director of the Lynch Syndrome Center Shares his Personal Connection to Lynch Syndrome

Because of his adopted family’s cancer history, the director of Dana-Farber’s Lynch Syndrome Center, Matt Yurgelun, MD, is uniquely invested in helping patients with Lynch syndrome — a common and often under-diagnosed inherited condition.

Eight of the 13 in his grandfather’s generation ultimately developed some form of cancer, and it wasn’t until later that Matt Yurgelun would understand why: Lynch syndrome, which increases one’s risk for a variety of cancers, runs in the family.

 “There is an old photograph of my grandfather and his siblings, and to see how many of them ultimately died young of cancer is heartbreaking,” Yurgelun says. “Contrast that with a current picture of the family, and since we’ve found the Lynch syndrome alteration, nobody has actually died of cancer.”

Family history guides a researcher’s path

Growing up, Yurgelun knew that his grandfather had died of something cancer-related, but he didn’t know the specifics. As he was working through undergrad, Yurgelun’s uncle, Dr. C. Richard Boland, a gastroenterologist studying colorectal cancers and Lynch syndrome, reached out to him.

“I eventually learned that my uncle was studying this because his father, my grandfather, had actually passed away after developing multiple colon cancers by the time he was in his early 40s,” says Yurgelun. “It turned out that cancer was kind of the family curse.”

Yurgelun’s uncle had been studying the family for decades, and at first was dismissed by many experts in the field.

“They told him that there wasn’t any such thing as inherited risk of colon cancer,” says Yurgelun.

Spurred by this revelation, Yurgelun hastily joined his uncle in his lab to help research inherited cancer risk. After identifying a possible mutational breakpoint, Yurgelun and his uncle swabbed the cheeks of family members during a reunion, collecting samples to see if they shared that breakpoint and possibly had Lynch syndrome.

Lynch syndrome explained

Lynch syndrome is caused by an inherited genetic mutation in one of five different genes, that can increase a person’s risk for a wide variety of cancers. It’s most commonly associated with an increased risk of colorectal and uterine cancers, but the list extends into ovarian, stomach, pancreatic, bile duct, and skin cancer as well.

It’s been found to be a common syndrome that can affect about 1 in 300 people.

“It’s probably very underrecognized,” says Yurgelun. “Some estimates say that 90-95% of people with Lynch syndrome don’t know that they have it.”

At Dana-Farber’s Lynch Syndrome Center, one of the largest and most comprehensive multidisciplinary cancer genetics centers in the region, Yurgelun and his colleagues evaluate patients that may have Lynch syndrome and help them come up with a plan for preventative care.

“Much of our work around Lynch syndrome is preventing cancer before it starts,” Yurgelun notes.

People with Lynch syndrome are often tested and diagnosed because they have been diagnosed with cancer or they have a family history of cancer, ultimately triggering a recommendation for genetic testing.

A promising future for prevention and treatment

Yurgelun and his team hope to gain a deeper understanding of the condition through research.

“We link five different genes to Lynch syndrome, and there are thousands of potential mutations that can present on the genes,” explains Yurgelun. “Historically we’ve lumped all of these into a single syndrome, but we are starting to understand now that each gene really has its own individual version of Lynch syndrome, which is allowing us to better individualize the care for those with Lynch syndrome.”

Lynch syndrome manifests in a wide variety of ways, and a one-size-fits-all approach to care will not always be effective in treating every patient and family. Yurgelun’s work aims to find ways to personalize each patient’s preventative plan.

“We could use an approach where we throw the kitchen sink at it, where we screen everyone in the family for a long list of cancers, but some of that ends up being overkill in some cases, and patients can develop screening fatigue,” says Yurgelun. “We’re learning ways in which we can be smarter and more sophisticated about our prevention.”

Using Dana-Farber’s comprehensive infrastructure and resources, the Lynch Syndrome Center is also monitoring patients and cases through the Lynch Syndrome Registry and Biobank to track lifestyle, genetic, and specimen data from people with the condition.

“It’s phenomenal to be doing this work at Dana-Farber since we have so many specialists who are well versed in genetics and who are at the top of their field in a whole variety of aspects of cancer care — whether that be surgery, chemotherapy treatment, psychosocial support, or lifestyle studies,” says Yurgelun.

Eventually, this data will hopefully lead to a better understanding of how to develop preventative treatments for patients diagnosed with Lynch syndrome, as well as ways physicians can catch cancer as early as possible if it develops.

“Many of our patients are more than willing to take part in this — not only for their own benefit, but also for the future generations of their families,” says Yurgelun.

Research can also be helpful in developing and implementing immunotherapies. Almost every cancer in a patient with Lynch syndrome displays a phenomenon called microsatellite instability (MSI). This is a very powerful predictor for advanced and metastatic cancers that can respond to immunotherapy.

The immune systems of patients with Lynch syndrome who haven’t had cancer sometimes exhibit responses to that MSI. This suggests that these patients’ immune systems are reacting to pre-cancerous formations in the body. This discovery has spurred cancer vaccine research for people with Lynch syndrome to prevent possible cancers that might develop because of it.

Thanks to the tireless efforts of passionate researchers and physicians like Yurgelun, the future for patients with Lynch syndrome, including his own family members, looks bright.