Lynch Syndrome – A Brief Story of the Father of Cancer Genetics

Lynch syndrome, which can cause various cancers, is an inherited syndrome.

The most common cancer associated with Lynch syndrome is colorectal cancer (large bowel = colon and rectum), but Lynch syndrome also predisposes patients to cancers of the small intestine, stomach, bile ducts, uterus, ovaries, ureter, and renal pelvis.

Lynch syndrome is caused by a mutation in 1 of the 4 genes responsible for DNA mismatch repair (MMR)—MLH1, MSH2, MSH6, or PMS2—specifically a germline (inherited) mutation.

Lynch syndrome is an autosomal dominant inherited disorder. In other words, it results from damage to chromosomes other than those determining sex. Individuals with the damaged gene have a high risk of developing cancer. However, not everyone carrying damaged genes associated with Lynch syndrome develops cancer.

Above is an example pedigree of an individual with Lynch syndrome. Children of a mother or father with Lynch syndrome have a 50% risk of having Lynch syndrome.

US National Comprehensive Cancer Network (US-NCCN) guidelines recommend genetic screening to identify Lynch syndrome in all patients with colorectal and endometrial (uterine) cancer, regardless of age at diagnosis. The guidelines also recommend considering tumor screening for MMR deficiency in sebaceous neoplasms and cancers of the small intestine, stomach, pancreas, bile ducts, brain, bladder, urothelium, and adrenal cortex.

The History of the Name Lynch Syndrome

Lynch syndrome is named after Dr Henry T. Lynch. Dr Lynch was born in 1928 in Lawrence, Massachusetts, USA. 

Dr Lynch served as a gunner in the South Pacific in the US Navy during the Second World War. On returning from the war, he completed high school and boxed professionally under the name “Hammerin' Hank.”

Dr Lynch eventually gave up boxing to continue his education. He earned a bachelor's degree at the University of Oklahoma, a master's degree in clinical psychology at the University of Denver, and a medical degree at the University of Texas in Galveston. 

In 1962, during his internal medicine residency at Creighton University in Omaha, Nebraska, Dr Lynch encountered the condition that would later bear his name.

Dr Lynch learned that a patient hospitalized for alcohol withdrawal had a family history of colorectal and endometrial cancer. Dr Lynch identified at least 21 family members diagnosed with cancer.

Dr Lynch called this family “Family N,” referring to Nebraska. At the same time, Dr Margery Shaw encountered a similar family in Michigan, called “Family M.” Dr Lynch and Dr Shaw published a scientific paper on both families in 1966. 

Dr Lynch published detailed findings on other such families in 1967 and 1971. His work built on earlier research by Dr Aldred Scott Warthin. In the late 1800s and early 1900s, Dr Warthin had described a family with a history of cancer as “Family G.” 

Dr Lynch initially called this family “Cancer Family Syndrome” because of their predisposition to cancer. He later coined the term “hereditary nonpolyposis colorectal cancer,” which remains an accepted name today. 

The genetic foundations of this phenomenon were subsequently identified, and Dr C. Richard Boland used the term “Lynch syndrome.” This described families with germline (inherited) mutations in MMR genes.

Dr Lynch spent his career at Creighton University, but was known as a doctor who spent extensive time with patients and their families at home and in community information settings. This career earned him the name “the father of cancer genetics.” Dr Lynch died in 2019 at 91.