Study Finds Many Lynch Syndrome Patients Remain Undiagnosed

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A new study by Cedars-Sinai cancer researchers aims to improve current screening to include lesser-recognized causes of Lynch syndrome, the most common cause of hereditary colorectal and endometrial cancers. May justify reconsideration of the guidelines. Their research today JNCCN-; National Comprehensive Cancer Network Journal, Guidelines conclude that a significant number of patients remain undiagnosed.

“People with Lynch syndrome usually have early-onset cancers, but unless they are diagnosed quickly, they are not properly followed up and monitored,” says Megan, director of translational genomics. Dr Hitchens said. Cedars-Sinai University Department of Biomedical Sciences and lead author of the study. “They may go on to have multiple different cancers before they are finally diagnosed. If we can identify when they had their first cancer, we can prevent further cancers from occurring and At least we’ll find it early.”

Many colorectal and endometrial cancers have what is called a mismatch repair deficiency. This means that the tumor formed due to mistakes in DNA copying during cell division.

In most cases of Lynch syndrome, this mismatch repair deficiency is caused by genetic mutations in DNA mismatch repair genes. However, mismatch repair defects can also be caused by something called methylation. This is a change in a gene called MLH1.

“Unlike mutations, methylation is not hardwired into the gene,” Hitchens said. “It’s like having an engine clogged with debris. There’s nothing wrong with the engine itself, but it clogs up and doesn’t work properly.”

MLH1 Methylation is present in 75% of mismatch repair-deficient tumors, Hitchens said. This defect is usually present only within the tumor. That is, the defect is not inherited and the patient does not have Lynch syndrome.

“However, in our study, we found that a small proportion of patients had methylation. teeth present in normal tissue. It is not limited to tumors. This makes the cells more susceptible to developing cancer,” Hitchens said, adding, “Because methylation is usually only present within tumors, these patients are automatically identified as non-Lynch patients and have Lynch syndrome.” “I never got a blood test to diagnose it,” he said.

To determine how often this occurs, the researchers examined data from two large, population-based, retrospective studies and tested blood DNA from all participating patients with mismatch repair-deficient colorectal cancer. bottom. Of the patients aged 55 and younger who had tumor methylation, 25-75% also had methylation in their blood, meaning they had Lynch syndrome but were undiagnosed.

In a previous study published in the journal Gynecologic Oncology, Hitchens and colleagues tested blood from endometrial cancer patients from the same patient population. They found that about 30% of endometrial cancer patients have intratumoral methylation. Also, 15% to 20% of people under the age of 50 have methylation in their blood, indicating Lynch syndrome, Hitchens said.

“Together, these studies suggest that this patient population will benefit from changes in screening guidelines,” said Dan Theodorescu, M.D., Ph.D., Director of Cedars-Sinai Cancer Center and PHASE ONE Special Chair. rice field. “Appropriate screening can potentially provide life-saving surveillance and subsequent early detection and treatment of cancer.”

At this time, Dr. Hitchens offers colorectal cancer patients younger than 56 years and patients with endometrial cancer younger than 50 years for additional screening for themselves and their parents, siblings, and adult children. I encourage people to ask. He also suggested that primary care providers and oncologists contact young patients in the last five years who test positive for MLH1 methylation for endometrial or colorectal tumors.

“We had endometrial cancer, colorectal cancer, were told it wasn’t Lynch syndrome, and then had colon cancer and other cancers that could have been prevented or at least detected early. We’ve been finding young patients who develop ,” Hitchens said. “These patients walk around unaware of the risks and should be made aware of that fact and given the option of being tested.”


Cedars-Sinai Medical Center

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