Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (endometrial cancer). Women with Lynch syndrome have a higher overall risk of developing cancer than men with the condition because of these cancers of the female reproductive system. Individuals with Lynch syndrome typically develop cancer in their forties or fifties.
People with Lynch syndrome may occasionally have noncancerous (benign) growths in the colon, called colon polyps. In individuals with this disorder, colon polyps occur at a younger age but not in greater numbers than they do in the general population.
In the United States, it is estimated that 1 in 279 individuals have a gene mutation associated with Lynch syndrome.
The MLH1, MSH2, MSH6, and PMS2 genes are involved in repairing errors that occur when DNA is copied in preparation for cell division (a process called DNA replication). Because these genes work together to fix DNA errors, they are known as mismatch repair (MMR) genes. Mutations in any of these genes prevent the proper repair of DNA replication errors. As the abnormal cells continue to divide, the accumulated errors can lead to uncontrolled cell growth and possibly cancer. Mutations in the MLH1 or MSH2 gene tend to lead to a higher risk (70 to 80 percent) of developing cancer in a person's lifetime, while mutations in the MSH6 or PMS2 gene have a lower risk (25 to 60 percent)of cancer development.
Mutations in the EPCAM gene also lead to impaired DNA repair, although the gene is not itself involved in this process. The EPCAM gene lies next to the MSH2 gene on chromosome 2 and certain EPCAM gene mutations cause the MSH2 gene to be turned off (inactivated). As a result, the MSH2 gene's role in DNA repair is impaired, which can lead to accumulated DNA errors and cancer development.
Although mutations in these genes predispose individuals to cancer, not all people with these mutations develop cancerous tumors.
Lynch syndrome cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the altered gene in each cell is sufficient to increase cancer risk. It is important to note that people with a mutation have an increased risk of cancer; not all people who inherit mutations in these genes will develop cancer.
- ACT Sheet: Family History ACT Sheet: Colon Cancer (Asymptomatic)
- Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004 Feb 18;96(4):261-8.
- What is genetic testing?
- Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 4
- Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 5
- Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 8
- Genetic Testing Registry: Lynch syndrome
- Genetic Testing Registry: Lynch syndrome I
- Genetic Testing Registry: Lynch syndrome II
- Hegde M, Ferber M, Mao R, Samowitz W, Ganguly A; Working Group of the American College of Medical Genetics and Genomics (ACMG) Laboratory Quality Assurance Committee. ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis). Genet Med. 2014 Jan;16(1):101-16. doi: 10.1038/gim.2013.166. Epub 2013 Dec 5.
- Weissman SM, Burt R, Church J, Erdman S, Hampel H, Holter S, Jasperson K, Kalady MF, Haidle JL, Lynch HT, Palaniappan S, Wise PE, Senter L. Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline. J Genet Couns. 2012 Aug;21(4):484-93. doi: 10.1007/s10897-011-9465-7. Epub 2011 Dec 14.
- cancer family syndrome
- familial nonpolyposis colon cancer
- hereditary nonpolyposis colorectal cancer
- hereditary nonpolyposis colorectal neoplasms
- National Cancer Institute: Colorectal Cancer
- National Cancer Institute: Genetics of Colorectal Cancer
- National Human Genome Research Institute: Learning About Colon Cancer
- National Human Genome Research Institute: The Genomic Services Research Program (GSRP): Study of People with Unexpected Genetic Results
- American Cancer Society: Colon and Rectum Cancer
- Centers for Disease Control and Prevention: Colorectal (Colon) Cancer
- Genetic Science Learning Center, University of Utah
- MalaCards: lynch syndrome
- Orphanet: Lynch syndrome
- Stanford Cancer Center
- Your Genome from Wellcome Genome Campus: What is Hereditary Non-Polyposis Colorectal Cancer?