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Tang, P. Lynch Syndrome. Encyclopedia. Available online: https://encyclopedia.pub/entry/5972 (accessed on 25 December 2024).
Tang P. Lynch Syndrome. Encyclopedia. Available at: https://encyclopedia.pub/entry/5972. Accessed December 25, 2024.
Tang, Peter. "Lynch Syndrome" Encyclopedia, https://encyclopedia.pub/entry/5972 (accessed December 25, 2024).
Tang, P. (2021, January 04). Lynch Syndrome. In Encyclopedia. https://encyclopedia.pub/entry/5972
Tang, Peter. "Lynch Syndrome." Encyclopedia. Web. 04 January, 2021.
Lynch Syndrome
Edit

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.

genetic conditions

1. Introduction

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.

2. Frequency

In the United States, it is estimated that 1 in 279 individuals have a gene mutation associated with Lynch syndrome.

3. Causes

Changes in the MLH1, MSH2, MSH6, PMS2, or EPCAM gene have been found in people 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.

4. Inheritance

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.

5. Other Names for This Condition

  • cancer family syndrome
  • familial nonpolyposis colon cancer
  • hereditary nonpolyposis colorectal cancer
  • hereditary nonpolyposis colorectal neoplasms
  • HNPCC

References

  1. Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP,Nakken S, Engel C, Aretz S, Jenkins MA, Sunde L, Bernstein I, Capella G, BalaguerF, Thomas H, Evans DG, Burn J, Greenblatt M, Hovig E, de Vos Tot Nederveen CappelWH, Sijmons RH, Bertario L, Tibiletti MG, Cavestro GM, Lindblom A, Della Valle A,Lopez-Köstner F, Gluck N, Katz LH, Heinimann K, Vaccaro CA, Büttner R, Görgens H,Holinski-Feder E, Morak M, Holzapfel S, Hüneburg R, Knebel Doeberitz MV, LoefflerM, Rahner N, Schackert HK, Steinke-Lange V, Schmiegel W, Vangala D, PylvänäinenK, Renkonen-Sinisalo L, Hopper JL, Win AK, Haile RW, Lindor NM, Gallinger S, LeMarchand L, Newcomb PA, Figueiredo JC, Thibodeau SN, Wadt K, Therkildsen C,Okkels H, Ketabi Z, Moreira L, Sánchez A, Serra-Burriel M, Pineda M, Navarro M,Blanco I, Green K, Lalloo F, Crosbie EJ, Hill J, Denton OG, Frayling IM, Rødland EA, Vasen H, Mints M, Neffa F, Esperon P, Alvarez K, Kariv R, Rosner G, PineroTA, Gonzalez ML, Kalfayan P, Tjandra D, Winship IM, Macrae F, Möslein G, Mecklin JP, Nielsen M, Møller P. Cancer risks by gene, age, and gender in 6350 carriersof pathogenic mismatch repair variants: findings from the Prospective LynchSyndrome Database. Genet Med. 2020 Jan;22(1):15-25. doi:10.1038/s41436-019-0596-9. Epub 2019 Jul 24. Erratum in: Genet Med. 2020Sep;22(9):1569. Citation on PubMed
  2. Hegde M, Ferber M, Mao R, Samowitz W, Ganguly A; Working Group of the AmericanCollege of Medical Genetics and Genomics (ACMG) Laboratory Quality AssuranceCommittee. ACMG technical standards and guidelines for genetic testing forinherited 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. Citation on PubMed
  3. Kohlmann W, Gruber SB. Lynch Syndrome. 2004 Feb 5 [updated 2018 Apr 12]. In:Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A,editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1211/ Citation on PubMed
  4. 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 EPCAMdeletions in Lynch syndrome. Hum Mutat. 2011 Apr;32(4):407-14. doi:10.1002/humu.21446. Epub 2011 Mar 1. Citation on PubMed
  5. 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. Citation on PubMed
  6. 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. Heritablesomatic 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. Citation on PubMed
  7. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003Mar 6;348(10):919-32. Review. Citation on PubMed
  8. 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. Citation on PubMed
  9. Martín-López JV, Fishel R. The mechanism of mismatch repair and the functionalanalysis of mismatch repair defects in Lynch syndrome. Fam Cancer. 2013Jun;12(2):159-68. doi: 10.1007/s10689-013-9635-x. Review. Citation on PubMed or Free article on PubMed Central
  10. 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. Epub2012 Aug 15. Citation on PubMed or Free article on PubMed Central
  11. Tamura K, Kaneda M, Futagawa M, Takeshita M, Kim S, Nakama M, Kawashita N,Tatsumi-Miyajima J. Genetic and genomic basis of the mismatch repair systeminvolved in Lynch syndrome. Int J Clin Oncol. 2019 Sep;24(9):999-1011. doi:10.1007/s10147-019-01494-y. Epub 2019 Jul 4. Review. Erratum in: Int J ClinOncol. 2019 Jul 31;:. Citation on PubMed
  12. Tanakaya K. Current clinical topics of Lynch syndrome. Int J Clin Oncol. 2019 Sep;24(9):1013-1019. doi: 10.1007/s10147-018-1282-7. Epub 2018 May 9. Review. Citation on PubMed
  13. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J, FishelR, 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 hereditarynonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. JNatl Cancer Inst. 2004 Feb 18;96(4):261-8. Citation on PubMed or Free article on PubMed Central
  14. 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 ofthe Americas on Inherited Colorectal Cancer joint practice guideline. J GenetCouns. 2012 Aug;21(4):484-93. doi: 10.1007/s10897-011-9465-7. Epub 2011 Dec 14. Citation on PubMed
  15. Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, Buchanan DD,Clendenning M, Rosty C, Ahnen DJ, Thibodeau SN, Casey G, Gallinger S, Le MarchandL, Haile RW, Potter JD, Zheng Y, Lindor NM, Newcomb PA, Hopper JL, MacInnis RJ.Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer.Cancer Epidemiol Biomarkers Prev. 2017 Mar;26(3):404-412. doi:10.1158/1055-9965.EPI-16-0693. Epub 2016 Oct 31. Citation on PubMed or Free article on PubMed Central
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