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Genetics Home Reference: your guide to understanding genetic conditions
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Lynch syndrome

Reviewed May 2013

What is Lynch syndrome?

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

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 (http://www.nchpeg.org/documents/crc/Basics%20of%20genetic%20testing.pdf)
  • GeneFacts: Lynch Syndrome: Management (http://genefacts.org/index.php?option=com_content&view=article&id=492:management&catid=113:lynch-syndrome&Itemid=665)
  • Gene Review: Lynch Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1211)
  • Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1838344)
  • Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1838333)
  • Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1833477)
  • Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 8 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2750471)
  • Genetic Testing Registry: Lynch syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0009405)
  • Genetic Testing Registry: Lynch syndrome I (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2936783)
  • Genetic Testing Registry: Lynch syndrome II (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1333991)
  • MedlinePlus Encyclopedia: Colon Cancer (http://www.nlm.nih.gov/medlineplus/ency/article/000262.htm)
  • National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes (http://www.cancer.gov/cancertopics/factsheet/Risk/genetic-testing)

You might also find information on the diagnosis or management of Lynch syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/lynch-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/lynch-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) 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.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

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 (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Lynch syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

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 ; hereditary ; inherit ; inherited ; intestine ; neoplasms ; population ; rectum ; stomach ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Annie Yu HJ, Lin KM, Ota DM, Lynch HT. Hereditary nonpolyposis colorectal cancer: preventive management. Cancer Treat Rev. 2003 Dec;29(6):461-70. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14585257?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):323-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16341812?dopt=Abstract)
  • Chung DC, Rustgi AK. The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann Intern Med. 2003 Apr 1;138(7):560-70. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12667026?dopt=Abstract)
  • Gene Review: Lynch Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1211)
  • 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. 2005 May 5;352(18):1851-60. (http://www.ncbi.nlm.nih.gov/pubmed/15872200?dopt=Abstract)
  • 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. 2011 Apr;32(4):407-14. doi: 10.1002/humu.21446. Epub 2011 Mar 1. (http://www.ncbi.nlm.nih.gov/pubmed/21309036?dopt=Abstract)
  • 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. 2007 Feb 21;99(4):291-9. (http://www.ncbi.nlm.nih.gov/pubmed/17312306?dopt=Abstract)
  • 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. 2009 Jan;41(1):112-7. doi: 10.1038/ng.283. Epub 2008 Dec 21. (http://www.ncbi.nlm.nih.gov/pubmed/19098912?dopt=Abstract)
  • Lucci-Cordisco E, Zito I, Gensini F, Genuardi M. Hereditary nonpolyposis colorectal cancer and related conditions. Am J Med Genet A. 2003 Nov 1;122A(4):325-34. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14518071?dopt=Abstract)
  • Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003 Mar 6;348(10):919-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12621137?dopt=Abstract)
  • Lynch HT, Lynch JF. What the physician needs to know about Lynch syndrome: an update. Oncology (Williston Park). 2005 Apr;19(4):455-63; discussion 463-4, 466, 469. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15938070?dopt=Abstract)
  • Martín-López JV, Fishel R. The mechanism of mismatch repair and the functional analysis of mismatch repair defects in Lynch syndrome. Fam Cancer. 2013 Jun;12(2):159-68. doi: 10.1007/s10689-013-9635-x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23572416?dopt=Abstract)
  • Peltomäki P. Lynch syndrome genes. Fam Cancer. 2005;4(3):227-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16136382?dopt=Abstract)
  • 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 2012. Eur J Hum Genet. 2013 Jan;21(1). doi: 10.1038/ejhg.2012.164. Epub 2012 Aug 15. (http://www.ncbi.nlm.nih.gov/pubmed/22892529?dopt=Abstract)
  • Rowley PT. Inherited susceptibility to colorectal cancer. Annu Rev Med. 2005;56:539-54. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15660526?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/14970275?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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2013
Published: February 23, 2015