Editing 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.[https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/autosomal-dominant-inheritance]
* 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