June 14, 2024
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June 14, 2024
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Linking Northern and Central NJ, Bronx, Manhattan, Westchester and CT

As a medical student, one of the things in which we reveled was eponyms. These are the names that are given to clinical signs, symptoms or diseases that usually follow the names of the discoverers. My friends and I spent many hours memorizing the eponyms for all sorts of entities, and at one point, I even carried around a small booklet in the pocket of my white jacket which was a catalogue of eponyms. (I know, I know—a nerd!). All of this so I could show off on rounds.

Many diseases and cancers are named after someone and it is certainly an honor to have this appellation take place—Li-Fraumeni syndrome, Paget’s disease, Burkitt lymphoma, Hodgkin lymphoma. Which brings us to our topic for today’s article, Lynch Syndrome.

Henry Lynch is known as the father of cancer genetics. I knew him for many years from various conferences and meetings—he was a large hulking man with a loud voice. He was born in 1928 and grew up in New York City. He lied about his age to join the Navy at age 16 during World War II and served as a gunner on a ship. After the war, he became a professional boxer for several years, but then went to the University of Oklahoma where he got his bachelor’s degree in 1951, and then a master’s degree in psychology from the University of Denver in 1952. He received his MD from the University of Texas at Galveston in 1960, followed by a residency in internal medicine at the University of Nebraska. He was briefly on the faculty at MD Anderson Cancer Center before going to Creighton University in Omaha in 1967 where he spent the remainder of his career.

Lynch noticed that some of his patients had family members who also had the same cancers. He hypothesized that cancer could be hereditary, and he began applying to the National Institutes of Health for grants to study this further, but these grants were mostly rejected—I suspect he did not know much about epidemiology or statistics, and certainly knew little about grantsmanship.

Despite this, Lynch went on compiling family histories and pedigrees of hundreds of patients and their families. With these data, he was able to recognize certain patterns that defined what he called genetic syndromes—early age at onset, specific patterns of cancers linked in syndromes, and Mendelian patterns of inheritance.

He was a tireless and passionate speaker on the subject. Ultimately people began to listen and his ideas regarding genetic syndromes gained widespread acceptance. He demonstrated the Mendelian inheritance pattern for breast and ovarian cancer that was later recognized as the syndrome caused by the BRCA genes. But he is best known for the most common form of hereditary colorectal cancer, also known as hereditary nonpolyposis colorectal cancer (HNPCC). This was given the eponym of Lynch Syndrome.

Lynch Syndrome is transmitted as an autosomal dominant (you only need one copy of the gene). Inheritance of the gene conveys a high risk not only for colorectal cancer, but also for endometrial cancer, small bowel cancer, ovarian cancer, gastric cancer, biliary tract cancer, and certain brain tumors. Carriers of the gene for Lynch Syndrome have a lifetime risk of colorectal cancer that is just over 50%.

This syndrome is associated with mutations in the genes that regulate DNA repair, so-called mismatch repair (MMR) genes. There are enzymes whose task is to review newly copied DNA during DNA replication and ensure that no errors have occurred—if there is a mismatch, these enzymes recognize that mismatch and repair it. Think of it as analogous to proofreading and copyediting. A mutation in one of these genes inactivates these enzymes and leads to the accumulation of mutations, increasing the risk of carcinogenesis.

The prevalence of these genes in the average-risk general population is not really known, but is probably roughly 1 in 300. Screening is not generally recommended. There do seem to be some founder mutations in the HNPCC genes that are more prevalent in Ashkenazi populations, but I do not believe they have occasioned a different screening recommendation. As always, the concerned reader should discuss this with his/her healthcare provider or a genetic counselor.


Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.

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