Lynch syndrome
- Also known as hereditary nonpolyposis colorectal carcinoma (HNPCC)
- Lynch syndrome preferred term since most patients will develop one or several adenomatous polyps
- Caused by inactivation of one of several DNA mismatch repair genes
- Genetics
- MMR genes: MLH1, MSH2, MSH6, PMS2
- Mutations in MLH1 and MSH2 account for up to 90% of LS cases
- Autosomal dominant
- NCI definition: autosomal dominant inheritance is a way a genetic trait or condition can be passed down from parent to child. One copy of a mutated (changed) gene from one parent can cause the genetic condition. A child who has a parent with the mutated gene has a 50% chance of inheriting that mutated gene.[1]
- Increased risk of cancer
- LS cancers form only after a second hit (by one of several genetic damage mechanisms) occurs within somatic tissue, which causes loss of function to the normal (wild-type) allele inherited from the unaffected parent
- This results in total loss of DNA MMR activity in that cell and subsequent microsatellite instability.
- Associated malignancies:
- Colon (most common)
- Endometrial (second most common)
- Urologic (3): Prostate, Urothelial, Adrenal
- Other: Stomach, Hepatobiliary, Small bowel, Ovarian, Brain (glioblastoma), Sebaceous, carcinomas
- Inconsistent: Pancreas, Breast
References
Giardiello, Francis M., et al. "Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer." Gastroenterology 147.2 (2014): 502-526.