MLH1 gene- Lynch Syndrome

Lynch syndrome

Men and women with Lynch syndrome 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.  The molecular genetics of Lynch syndrome are well understood.  The condition is caused by a mutation in one of the mismatch repair genes, most often MLH1, MSH2, MSH6, or PMS2.  Mutations in EPCAM can also cause Lynch syndrome. Several hundred mutations in the mismatch repair genes 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 mismatch repair protein that cannot perform its normal function. When the mismatch repair 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.

Mutations in mismatch repair genes 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