Lynch syndrome

Lynch syndrome is caused by mutations in at least 5 genes ( MLH1 , MSH2, MSH6, PMS2 _or EPCAM_ ). All of these genes are involved in the repair of mistakes made when DNA is copied (DNA replication) in preparation for cell division. Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the accumulated mistakes can lead to uncontrolled cell growth and possibly cancer. Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors.

The diagnosis of Lynch syndrome can be made on the basis of the Amsterdam Clinical Criteria or on the basis of molecular genetic testing for germline mutations in one of several mismatch repair (MMR) genes.

To read detailed diagnostic strategies, please visit the following link from GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1211/#hnpcc.Diagnosis

Lynch syndrome cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the mutated gene in each cell is sufficient to increase a person's cancer risk. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer.

Lynch syndrome is a genetic disorder that causes an increased risk of developing certain types of cancer such as colon and rectal cancer, as well as cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women with Lynch syndrome also have a high risk of developing uterine cancer (also called endometrial cancer) and ovarian cancer. Even though the disorder was originally described as not involving noncancerous (benign) growths (polyps) in the colon, people with Lynch syndrome may occasionally have colon polyps. Lynch syndrome has an autosomal dominant pattern of inheritance and is caused by a mutation in the MLH1, MSH2, MSH6, PMS2 or EPCAM gene. Treatment of colon cancer is surgical removal of the affected part of the colon (colectomy). People with Lynch syndrome should have routine colonoscopies.

Lynch syndrome is an inherited condition that increases the chance to develop certain types of cancers (a cancer predisposition syndrome). In the past, this condition was divided into two subtypes: Lynch syndrome 1 referred to a condition that increased the chance of developing colon cancer only and Lynch syndrome 2 referred to a condition that increased the chance of developing cancers other than colon cancer, such as cancers of the uterus, stomach, biliary tract and pancreas, and urinary tract. However, it is now known that both Lynch syndrome 1 and Lynch syndrome 2 are caused by mutations in the same genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). Because the underlying genetic cause is similar for both subtypes, they are now referred to as one condition, "Lynch syndrome".

The Hereditary Non-Polyposis Colon Cancer test is a panel which includes testing for MLH1-Related Hereditary Non-Polyposis Colon Cancer, MLH3-Related Hereditary Non-Polyposis Colon Cancer, MSH2-Related Hereditary Non-Polyposis Colon Cancer, MSH6-Related Hereditary Non-Polyposis Colon Cancer, PMS1-Related Hereditary Non-polyposis Colon Cancer, and PMS2-Related Hereditary Non- Polyposis Colon Cancer.

GeneTests lists laboratories offering clinical genetic testing for this condition. Clinical genetic tests are ordered to help diagnose a person or family and to aid in decisions regarding medical care or reproductive issues. Talk to your health care provider or a genetic professional to learn more about your testing options.

Lynch Syndrome International (LSI) Web site lists Lynch syndrome clinical trials and patient registries. Click on the link above to view the list.

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative, launched by the CDC National Office of Public Health Genomics developed an evidence report for Lynch syndrome entitled, Genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives.