Lynch syndrome caused by germline deletions in the EPCAM gene
EPCAM is a gene that sits next to the MSH2 gene on chromosome 2. Germline deletions in the 5’ end of EPCAM (the end closest to MSH2) cause inactivation of the MSH2 gene, one of the mismatch repair genes classically linked to the Lynch syndrome. These deletions cause the production of an 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 or another part of the body. Men and women with Lynch syndrome have up to a75% lifetime risk to develop 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 may also have an increased lifetime risk for endometrial cancer, but this risk appears to be much lower than what is typically seen with germline mutations in the mismatch repair genes. The risk for other tumor types typically seen in the Lynch syndrome is currently not thought to be increased. Germline deletions in EPCAM were only recently discovered as a cause of Lynch syndrome, therefore clarification of the risks of extra-colonic cancers in this condition will likely occur as more individuals and families are identified.
Deletions in EPCAM 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 http://kintalk.org/group/lynch-syndrome-2