Authors' recommendations: Lynch syndrome is a form of inherited cancer that is caused by sequence variants in 1 of 4 mismatch repair (MMR) genes, mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). More recently, variants in the epithelial cell adhesion molecule (EPCAM) gene have been identified as a cause of Lynch syndrome. Lynch syndrome is inherited as an autosomal dominant condition, 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 and ovarian cancers. Other cancers, including stomach, small bowel, urothelium (layer of tissue lining the urinary tract), biliary tract, and brain are also more prevalent in 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 endometrial cancer (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%), and women have a lifetime chance of EC of 35% (lifetime general population risk is 3%), with many affected individuals presenting at a young age. Screening to detect carriers of sequence variants in the MMR genes that cause Lynch syndrome is clinically important, as regular colonoscopies in carriers 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 affected women may be considered. Once a proband (first relative diagnosed in a family) with Lynch syndrome has been identified, the proband's 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. The original Amsterdam and revised Amsterdam (Amsterdam II) criteria were developed to clinically identify Lynch syndrome in a research setting. After the introduction of the Amsterdam criteria, much research was performed to understand the genetic foundation and molecular diagnosis of Lynch syndrome. An outcome of this research was the introduction of testing for microsatellite instability (MSI) to screen for Lynch syndrome, which led to the development of the original and revised Bethesda guidelines to aid physicians in the use of this technology. Both guidelines highlight the importance of early-onset familial cancers, primarily CRC, and uterine and other extracolonic cancers in the evaluation of Lynch syndrome.

Project Status: Completed

Year Published: 2014

URL for published report: The report may be purchased from: http://www.hayesinc.com/hayes/crd/?crd=17213

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