MSH2 Gene: Lynch Syndrome

MSH2 Gene- Lynch Syndrome

Lynch syndrome was reviewed in detail, including the fact that men and women with the condition have up to a 75% lifetime risk of developing colorectal cancer.  Moreover, this syndrome is associated with a 30% risk of a second primary colorectal cancer arising within 10 years of the first.  Women also have up to a 71% lifetime risk for endometrial cancer.  Persons with Lynch syndrome are also at increased risk for other cancers that include cancer of the urinary tract, ovary, stomach, small intestine, hepatobiliary tract, skin, and brain.  Several hundred mutations in the MSH2 gene that predispose people to colorectal cancer and other Lynch syndrome-associated cancers have been found. These mutations may cause the production of an abnormally short or inactivated MSH2 protein that cannot perform its normal function. When the MSH2 protein is absent or ineffective, the number of mistakes that are left unrepaired during cell division increases substantially. If the cells continue to divide, errors accumulate in DNA; the cells become unable to function properly and may form a tumor in the colon, endometrium or another part of the body.

The most up to date information about risks for extra-colonic and extra-endometrial cancers in carriers of MSH2 mutations as reported by Watson et al 2008 was discussed, and are as follows:  Urinary Tract Cancer: Men-28%, women 12%.  Ovarian Cancer: 8-12%.  Gastric Cancer: 5%.  Small Bowel Cancer: 3-6%.  Pancreatic/biliary Cancer: 4%.  Brain Cancer (usually glioblastoma): 2.5%.  Individuals with MSH2 mutations are also at an increased risk for sebaceous skin tumors, such as sebaceous adenoma, sebaceous carcinoma, and keratoacanthoma.  Exact risks for these rare skin tumors remain largely unknown.

Mutations in MSH2 are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation.

To learn more about Lynch syndrome please visit our Lynch Syndrome group