Authors' objectives: Lynch syndrome is a form of inherited cancer that is caused by germline sequence variants in 1 of 4 mismatch repair (MMR) genes, mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). More recently, variants in the epithelial cell adhesion molecule (EPCAM) gene have also been identified as a cause of Lynch syndrome. Lynch syndrome is inherited in an autosomal dominant fashion, meaning that a variant must be present in only 1 copy of the gene for the individual to be at risk of developing the condition. Sequence variants in the MMR genes increase the lifetime risk of a number of cancers, especially colorectal cancer (CRC), but also endometrial cancer (EC) and ovarian cancer. Other cancers, including stomach, small bowel, urothelium (layer of tissue lining the urinary tract), biliary tract, and brain cancer are also more prevalent in families with this condition. Lynch syndrome accounts for 2% to 5% of approximately 150,000 cases of CRC and 2% to 4% of approximately 50,000 cases of EC diagnosed each year in the United States. The syndrome is associated with a lifetime chance of 45% for CRC (lifetime general population risk is 5% to 6%), and women have a 35% lifetime risk of EC (lifetime general population risk is 3%), with many affected individuals presenting at a young age. This report will focus on genetic testing for Lynch syndrome rather than the aspects of tumor screening and the population to be screened, which are the focus of the companion Hayes Genetic Test Evaluation Report titled Screening for Lynch Syndrome.

Authors' recommendations: Screening to detect carriers of sequence variants in the MMR genes that cause Lynch syndrome is clinically important, as regular colonoscopies prompted by positive screening results have been shown to reduce the risk of CRC and the mortality associated with it. In addition, there is evidence that screening for other Lynch syndrome–associated cancers is indicated, and risk-reducing hysterectomy in carrier women may be considered. Once a proband (first-degree relative diagnosed in a family) with Lynch syndrome has been identified, relatives can be informed regarding their risks, and make decisions to undergo genetic testing for Lynch syndrome with the assistance of genetic counselors. Thus, risk assessment, surveillance, and prevention can extend to multiple relatives within a family, based on a single individual's Lynch syndrome status. This is referred to as a cascade effect. Direct gene testing for Lynch syndrome is usually a combination of DNA sequencing and a method to detect large rearrangements such as insertions, deletions, and duplications of the MMR genes. In some cases, EPCAM gene testing may be indicated. Multiple algorithms to guide screening and testing for Lynch syndrome have been developed by various groups, including the National Comprehensive Cancer Network (NCCN).

Project Status: Completed

Year Published: 2014

URL for published report: The report may be purchased from: http://www.hayesinc.com/hayes/crd/?crd=17393

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

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Contact Email: saleinfo@hayesinc.com

Copyright: 2014 Winifred S. Hayes, Inc