Lynch syndrome. What is Lynch syndrome? How common is Lynch syndrome? What genes are related to Lynch syndrome?

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1 1 of :57 AM What is Lynch syndrome? Lynch syndrome A service of the U.S. National Library of Medicine Reviewed May 2013 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, upper urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (the endometrium). People with Lynch syndrome may occasionally have noncancerous (benign) growths (polyps) in the colon, called colon polyps. In individuals with this disorder, colon polyps occur earlier but not in greater numbers than they do in the general population. How common is Lynch syndrome? In the United States, about 140,000 new cases of colorectal cancer are diagnosed each year. Approximately 3 to 5 percent of these cancers are caused by Lynch syndrome. What genes are related to Lynch syndrome? Variations in the MLH1, MSH2, MSH6, PMS2, or EPCAM gene increase the risk of developing Lynch syndrome. The MLH1, MSH2, MSH6, and PMS2 genes are involved in the repair of mistakes that occur when DNA is copied in preparation for cell division (a process called DNA replication). 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. 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; certain EPCAM gene mutations cause the MSH2 gene to be turned off (inactivated), interrupting DNA repair and leading to accumulated DNA mistakes. Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors. Related Gene(s) Changes in these genes are associated with Lynch syndrome. EPCAM MLH1 MSH2 MSH6 PMS2

2 2 of :57 AM How do people inherit Lynch syndrome? 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 inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer. Where can I find information about diagnosis or management of Lynch syndrome? These resources address the diagnosis or management of Lynch syndrome and may include treatment providers. American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer ( GeneFacts: Lynch Syndrome: Management ( content&view=article&id=492:management&catid=113:lynch-syndrome&itemid=665) Gene Review: Lynch Syndrome ( Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 3 ( 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 ( C ) Genetic Testing Registry: Lynch syndrome I ( C ) Genetic Testing Registry: Lynch syndrome II ( C ) MedlinePlus Encyclopedia: Colon Cancer ( htm) National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes ( You might also find information on the diagnosis or management of Lynch syndrome in Educational resources ( and Patient support ( General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing ( particularly the difference between clinical tests and research tests ( researchtesting).

3 3 of :57 AM To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook. Where can I find additional information about Lynch syndrome? You may find the following resources about Lynch syndrome helpful. These materials are written for the general public. MedlinePlus - Health information Encyclopedia: Colon Cancer ( htm) Health Topic: Cancer--Living with Cancer ( cancerlivingwithcancer.html) Health Topic: Colorectal Cancer ( colorectalcancer.html) Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases ( Additional NIH Resources - National Institutes of Health National Cancer Institute: Colon and Rectal Cancer ( types/colon-and-rectal) National Cancer Institute: Genetics of Colorectal Cancer ( cancertopics/pdq/genetics/colorectal/healthprofessional/page2) National Human Genome Research Institute: Learning About Colon Cancer ( NIH Senior Health: Colorectal Cancer ( colorectalcancerdefined/01.html) Educational resources - Information pages American Cancer Society: Colon and Rectum Cancer ( colonandrectumcancer/detailedguide/index) CDC: Colorectal (Colon) Cancer ( Cleveland Clinic ( hnpcc.aspx) Disease InfoSearch: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) ( HNPCC%29/3371) Genetic Science Learning Center, University of Utah ( content/disorders/whataregd/colon/index.html) Mayo Clinic ( My46 Trait Profile ( type=profile)

4 4 of :57 AM Orphanet ( Stanford Cancer Center ( hpncc.html) Patient support - For patients and families Colon Cancer Alliance ( Colon Cancer Alliance for Research and Education for Lynch Syndrome ( Colorectal Cancer Coalition ( Lynch Syndrome International ( You may also be interested in these resources, which are designed for healthcare professionals and researchers. Gene Reviews - Clinical summary ( Genetic Testing Registry - Repository of genetic test information Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 3 ( 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 ( C ) Genetic Testing Registry: Lynch syndrome I ( C ) Genetic Testing Registry: Lynch syndrome II ( C ) ClinicalTrials.gov - Linking patients to medical research ( cond=%22hereditary%20nonpolyposis%20colorectal%20cancer%22%20or%20%22 colorectal%20neoplasms%2c%20hereditary%20nonpolyposis%22) PubMed - Recent literature ( syndrome%5btiab%5d)%20and%20english%5bla%5d%20and%20human%5bmh%5d %20AND%20%22last%20360%20days%22%5Bdp%5D) OMIM - Genetic disorder catalog COLORECTAL CANCER ( LYNCH SYNDROME I (

5 5 of :57 AM What other names do people use for Lynch syndrome? cancer family syndrome familial nonpolyposis colon cancer hereditary nonpolyposis colorectal cancer hereditary nonpolyposis colorectal neoplasms HNPCC For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook. What if I still have specific questions about Lynch syndrome? Ask the Genetic and Rare Diseases Information Center ( What glossary definitions help with understanding Lynch syndrome? autosomal ; autosomal dominant ; benign ; cancer ; cell ; cell division ; chromosome ; colon ; colorectal ; DNA ; DNA repair ; DNA replication ; endometrium ; familial ; gallbladder ; gene ; intestine ; neoplasms ; population ; rectum ; stomach ; syndrome You may find definitions for these and many other terms in the Genetics Home Reference Glossary ( References Annie Yu HJ, Lin KM, Ota DM, Lynch HT. Hereditary nonpolyposis colorectal cancer: preventive management. Cancer Treat Rev Dec;29(6): Review. ( pubmed/ ?dopt=abstract) Bandipalliam P. Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer. 2005;4(4): Review. ( Chung DC, Rustgi AK. The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann Intern Med Apr 1;138(7): Review. ( pubmed/ ?dopt=abstract) Gene Review: Lynch Syndrome ( Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med May 5;352(18): ( Kuiper RP, Vissers LE, Venkatachalam R, Bodmer D, Hoenselaar E, Goossens M, Haufe A, Kamping E, Niessen RC, Hogervorst FB, Gille JJ, Redeker B, Tops CM, van Gijn ME, van den Ouweland AM, Rahner N, Steinke V, Kahl P, Holinski-Feder E, Morak M, Kloor M, Stemmler S, Betz B, Hutter P, Bunyan DJ, Syngal S, Culver JO, Graham T, Chan TL, Nagtegaal ID, van Krieken JH, Schackert HK, Hoogerbrugge N, van Kessel AG, Ligtenberg MJ. Recurrence and variability of germline EPCAM deletions in Lynch syndrome. Hum Mutat Apr;32(4): doi: /humu Epub 2011 Mar 1. (

6 6 of :57 AM Lagerstedt Robinson K, Liu T, Vandrovcova J, Halvarsson B, Clendenning M, Frebourg T, Papadopoulos N, Kinzler KW, Vogelstein B, Peltomäki P, Kolodner RD, Nilbert M, Lindblom A. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst Feb 21;99(4): ( Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, Lee TY, Bodmer D, Hoenselaar E, Hendriks-Cornelissen SJ, Tsui WY, Kong CK, Brunner HG, van Kessel AG, Yuen ST, van Krieken JH, Leung SY, Hoogerbrugge N. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet Jan;41(1): doi: /ng.283. Epub 2008 Dec 21. ( pubmed/ ?dopt=abstract) Lucci-Cordisco E, Zito I, Gensini F, Genuardi M. Hereditary nonpolyposis colorectal cancer and related conditions. Am J Med Genet A Nov 1;122A(4): Review. ( Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med Mar 6;348(10): Review. ( Lynch HT, Lynch JF. What the physician needs to know about Lynch syndrome: an update. Oncology (Williston Park) Apr;19(4):455-63; discussion 463-4, 466, 469. Review. ( Martín-López JV, Fishel R. The mechanism of mismatch repair and the functional analysis of mismatch repair defects in Lynch syndrome. Fam Cancer Jun;12(2): doi: /s x. ( Peltomäki P. Lynch syndrome genes. Fam Cancer. 2005;4(3): Review. ( Rahner N, Steinke V, Schlegelberger B, Eisinger F, Hutter P, Olschwang S. Clinical utility gene card for: Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) - update Eur J Hum Genet Jan;21(1). doi: /ejhg Epub 2012 Aug 15. ( pubmed/ ?dopt=abstract) Rowley PT. Inherited susceptibility to colorectal cancer. Annu Rev Med. 2005;56: Review. ( 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 Feb 18;96(4): ( pubmed/ ?dopt=abstract) The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( handbook/consult/findingprofessional) in the Handbook. Reviewed: May 2013 Published: November 4, 2013

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