Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)

Excerpt

The Epidemiology of the Syndrome

Colorectal cancer is the third-most common cancer in men and women and the second leading cause of cancer mortality in the United States, with an estimated 152,020 new cases and 52,550 deaths in 2023. While most colorectal cancers are sporadic, inherited mutations cause approximately 5% to 10% of cases. The most common hereditary form of colorectal cancer is Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC). Identifying patients with Lynch syndrome is important because their lifetime risk of colorectal cancer is 80%, and up to 60% for endometrial cancer. Other primary cancers part of Lynch syndrome include gastric, ovarian, small bowel, urothelial (ureter, renal pelvis, and bladder), prostate, biliary tract, pancreatic, adrenocortical, brain cancers (glioblastoma), sebaceous gland adenomas, and keratoacanthomas.

The History of Lynch Syndrome

In 1962, a medical intern named Henry Lynch learned that a young hospitalized farm worker suffering from alcohol poisoning was certain he would die young of cancer due to the prevalence of cancer in his family. Dr. Lynch decided to investigate this family. He bought a camper van equipped with basic laboratory instruments. He spent weekends for the next 2 years touring rural Nebraska, Kansas, and Missouri, collecting medical records, histories, pathology reports, and blood samples from extended family members. He discovered that an unusually high number died of colon cancer before age 50. He could not find any plausible explanation save for genetic transmission.

He presented his findings in 1964 and applied for several grants to allow him to investigate further, but was consistently turned down as these cancers were attributed to environmental causes. Dr Lynch continued his research, but his theories were widely discredited until molecular genetics techniques developed in the 1980s led to the discovery of the mismatch repair gene deficiencies and associated microsatellite instabilities found in these heritable cancers. HNPCC was renamed Lynch syndrome in his honor in 1984. Dr Lynch, the father of cancer genetics, is credited with facilitating many breakthroughs in cancer genetics, including identifying the breast-ovarian cancer syndrome and the BRCA genes and creating the entire field of cancer genomics.