Lynch Syndrome: Diagnosis, Cancer Risks, and Lifesaving Screening Strategies

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• What Is Lynch Syndrome?
• The History of Lynch Syndrome Discovery
• Genetic Causes of Lynch Syndrome
• How Lynch Syndrome Is Diagnosed
• Cancer Risks Associated With Lynch Syndrome
• Lynch Syndrome Screening Recommendations
• Treatment Options for Lynch Syndrome Patients
• Full Transcript

What Is Lynch Syndrome?

Lynch syndrome is a hereditary condition that significantly increases the risk of developing colorectal cancer and several other cancers at younger ages. Dr. C. Richard Boland, MD, explains that while most colon cancer cases aren't inherited, Lynch syndrome represents an important genetic exception that requires specialized care.

The History of Lynch Syndrome Discovery

Dr. C. Richard Boland, MD, describes how medical understanding of hereditary colon cancer evolved dramatically. Before 1993, only familial adenomatous polyposis (FAP) was recognized, characterized by hundreds of colon polyps. Dr. Henry Lynch pioneered research into non-polyposis hereditary colon cancer families, though the condition remained controversial until 1993 when researchers discovered microsatellite instability - the genetic signature of Lynch syndrome.

Genetic Causes of Lynch Syndrome

Lynch syndrome results from germline mutations in DNA mismatch repair genes. Dr. C. Richard Boland, MD, identifies four specific genes involved: MSH2, MLH1, MSH6, and PMS2. While all cause Lynch syndrome, each gene mutation produces slightly different clinical manifestations. This genetic understanding allows for precise diagnosis and personalized screening approaches.

How Lynch Syndrome Is Diagnosed

Diagnosis begins with recognizing family history patterns or early-onset cancers. Dr. C. Richard Boland, MD, emphasizes that genetic testing for microsatellite instability and specific gene mutations now provides definitive diagnosis. The discovery of these biomarkers in 1993 revolutionized Lynch syndrome identification, ending decades of diagnostic uncertainty.

Cancer Risks Associated With Lynch Syndrome

While best known for colorectal cancer risk, Lynch syndrome increases susceptibility to several malignancies. Patients may develop endometrial, ovarian, stomach, small intestine, hepatobiliary tract, urinary tract, brain, and skin cancers at higher rates than the general population, often at younger ages.

Lynch Syndrome Screening Recommendations

Dr. C. Richard Boland, MD, stresses that regular screening dramatically improves outcomes for Lynch syndrome patients. Colonoscopy should begin at age 20-25 or 2-5 years before the youngest colon cancer case in the family. Annual colonoscopies are recommended, along with specialized screening for other at-risk organs based on the specific gene mutation involved.

Treatment Options for Lynch Syndrome Patients

While Lynch syndrome cannot be cured, proactive management significantly reduces cancer risks and improves life expectancy. Options include enhanced surveillance, preventive surgeries in select cases, and consideration of immunotherapy for Lynch syndrome-related cancers, which often respond well to these newer treatments due to their specific genetic characteristics.

Full Transcript

Dr. Anton Titov, MD: What are the symptoms of Lynch syndrome? How is Lynch syndrome diagnosed? Lynch syndrome life expectancy can be good, but regular colon cancer screening is needed.

Let's start with Lynch syndrome. Most colorectal cancer cases are not inherited, but there is a particular familial colorectal cancer syndrome called Lynch syndrome. Lynch syndrome causes colon cancer in much younger patients. Lynch syndrome also increases the frequency of some other cancers.

Dr. Anton Titov, MD: You are a major expert in Lynch syndrome. What is Lynch syndrome? How do people usually find out that they have Lynch syndrome? What are the consequences of Lynch syndrome diagnosis for screening and treatment of colorectal cancer?

Dr. C. Richard Boland, MD: I think we need to have a historical perspective on how we figured out what the hereditary colon cancer syndromes were. In the past, doctors thought that the only familial form of colorectal cancer was familial adenomatous polyposis - it has a very distinct phenotype. Patients have hundreds or even thousands of polyps in the colon.

The first case of familial colon cancer was reported in 1913 by a University of Michigan pathologist. In the 1960s and 1970s, it was clear that there were some familial colorectal cancer families that did not have polyposis. They had something else.

Dr. Henry Lynch understood the significance of that story. I also started to research familial colon cancer. But from the late 1960s and early 1970s until 1993, there were disputes about whether such an inherited colon cancer disease existed, because we had no biomarker to confirm we were dealing with an inherited colon cancer syndrome.

In 1993, the molecular signature called microsatellite instability was discovered. It was immediately linked to hereditary colon cancer. Suddenly we were able to identify a group of families with hereditary colon cancer.

Within 9 months, hereditary colon cancer was linked to several DNA mismatch repair genes. At this time, Lynch syndrome is the hereditary colorectal cancer syndrome caused by a germline mutation in a DNA mismatch repair gene.

There are 4 genes that cause Lynch syndrome: MSH2, MLH1, MSH6 and PMS2. Any of these genes can cause Lynch syndrome, although the clinical manifestations are slightly different depending on which gene mutation causes Lynch syndrome in a patient.