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Lynch syndrome 5(LYNCH5)

MedGen UID:
318886
Concept ID:
C1833477
Disease or Syndrome
Synonyms: Colorectal cancer, hereditary nonpolyposis, type 5; Hereditary non-polyposis colorectal cancer, type 5; LYNCH5
 
Gene (location): MSH6 (2p16.3)
 
Monarch Initiative: MONDO:0013710
OMIM®: 614350

Definition

Lynch syndrome-5 (LYNCH5), or hereditary nonpolyposis colorectal cancer type 5 (HNPCC5), is a cancer predisposition syndrome characterized by onset of colorectal cancer and/or extracolonic cancers, particularly endometrial cancer, usually in mid-adulthood. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Castellsague et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of Lynch syndrome, see 120435. [from OMIM]

Additional description

From MedlinePlus Genetics
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. In individuals with Lynch syndrome who develop cancer, the cancer typically occurs 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.  https://medlineplus.gov/genetics/condition/lynch-syndrome

Clinical features

From HPO
Ovarian neoplasm
MedGen UID:
181539
Concept ID:
C0919267
Neoplastic Process
A tumor (abnormal growth of tissue) of the ovary.
Endometrial carcinoma
MedGen UID:
96903
Concept ID:
C0476089
Neoplastic Process
A carcinoma of the endometrium, the mucous lining of the uterus.
Neoplasm of the pancreas
MedGen UID:
18279
Concept ID:
C0030297
Neoplastic Process
A tumor (abnormal growth of tissue) of the pancreas.
Hereditary nonpolyposis colorectal carcinoma
MedGen UID:
870541
Concept ID:
C4024989
Neoplastic Process

Professional guidelines

PubMed

Taieb J, Svrcek M, Cohen R, Basile D, Tougeron D, Phelip JM
Eur J Cancer 2022 Nov;175:136-157. Epub 2022 Sep 14 doi: 10.1016/j.ejca.2022.07.020. PMID: 36115290
US Preventive Services Task Force, Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Krist AH, Kubik M, Li L, Ogedegbe G, Owens DK, Pbert L, Silverstein M, Stevermer J, Tseng CW, Wong JB
JAMA 2021 May 18;325(19):1965-1977. doi: 10.1001/jama.2021.6238. PMID: 34003218
Brand RE, Lynch HT
Endocrinol Metab Clin North Am 2006 Jun;35(2):405-15, xi. doi: 10.1016/j.ecl.2006.02.015. PMID: 16632102

Curated

UK NICE Guideline NG151, Colorectal cancer, 2021

UK NICE Diagnostics Guidance DG42, Testing strategies for Lynch syndrome in people with endometrial cancer, 2020

American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, MLH1, MSH2, MSH6, PMS2, EPCAM Pathogenic Variants, Lynch Syndrome (Hereditary Non-polyposis Colon Cancer [HNPCC]), 2019

Recent clinical studies

Etiology

Vibert R, Hasnaoui J, Perrier A, Lefebvre A, Colas C, Dhooge M, Basset N, Chansavang A, Desseignes C, Duval A, Farelly S, Hamzaoui N, Laurent-Puig P, Metras J, Moliere D, Muleris M, Netter J, Touat M, Bielle F, Labreche K, Nicolle R, Perkins G, Warcoin M, Coulet F, Benusiglio PR
Eur J Hum Genet 2023 Sep;31(9):1078-1082. Epub 2023 Apr 24 doi: 10.1038/s41431-023-01367-z. PMID: 37088804Free PMC Article
Mori G, Pasca MR
Int J Mol Sci 2021 Jan 28;22(3) doi: 10.3390/ijms22031312. PMID: 33525662Free PMC Article
Cerretelli G, Ager A, Arends MJ, Frayling IM
J Pathol 2020 Apr;250(5):518-531. doi: 10.1002/path.5422. PMID: 32141610
Biller LH, Syngal S, Yurgelun MB
Fam Cancer 2019 Apr;18(2):211-219. doi: 10.1007/s10689-018-00117-1. PMID: 30627969Free PMC Article
Gelsomino F, Barbolini M, Spallanzani A, Pugliese G, Cascinu S
Cancer Treat Rev 2016 Dec;51:19-26. Epub 2016 Oct 27 doi: 10.1016/j.ctrv.2016.10.005. PMID: 27838401

Diagnosis

Vibert R, Hasnaoui J, Perrier A, Lefebvre A, Colas C, Dhooge M, Basset N, Chansavang A, Desseignes C, Duval A, Farelly S, Hamzaoui N, Laurent-Puig P, Metras J, Moliere D, Muleris M, Netter J, Touat M, Bielle F, Labreche K, Nicolle R, Perkins G, Warcoin M, Coulet F, Benusiglio PR
Eur J Hum Genet 2023 Sep;31(9):1078-1082. Epub 2023 Apr 24 doi: 10.1038/s41431-023-01367-z. PMID: 37088804Free PMC Article
Calvello M, Bonanni B
Eur J Cancer Prev 2023 Sep 1;32(5):413-414. Epub 2023 Mar 21 doi: 10.1097/CEJ.0000000000000795. PMID: 36942845
Peltomäki P, Nyström M, Mecklin JP, Seppälä TT
Gastroenterology 2023 Apr;164(5):783-799. Epub 2023 Jan 24 doi: 10.1053/j.gastro.2022.08.058. PMID: 36706841
McSweeney K, Boldison E
Histopathology 2021 Nov;79(5):687-689. doi: 10.1111/his.14444. PMID: 34224174
Biller LH, Syngal S, Yurgelun MB
Fam Cancer 2019 Apr;18(2):211-219. doi: 10.1007/s10689-018-00117-1. PMID: 30627969Free PMC Article

Therapy

Dharwadkar P, Zaki TA, Murphy CC
Hematol Oncol Clin North Am 2022 Jun;36(3):449-470. Epub 2022 May 13 doi: 10.1016/j.hoc.2022.02.005. PMID: 35577711Free PMC Article
Herrington CS, Poulsom R, Coates PJ
J Pathol 2020 Apr;250(5):475-479. doi: 10.1002/path.5425. PMID: 32346919
Biller LH, Syngal S, Yurgelun MB
Fam Cancer 2019 Apr;18(2):211-219. doi: 10.1007/s10689-018-00117-1. PMID: 30627969Free PMC Article
Kampmeyer C, Nielsen SV, Clausen L, Stein A, Gerdes AM, Lindorff-Larsen K, Hartmann-Petersen R
Genes Chromosomes Cancer 2017 Dec;56(12):823-831. Epub 2017 Sep 6 doi: 10.1002/gcc.22487. PMID: 28779490
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group
JAMA 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. PMID: 26903337

Prognosis

Utikal J, Nagel P, Müller V, Becker JC, Dippel E, Frisman A, Gschnell M, Griewank K, Hadaschik E, Helbig D, Hillen U, Leiter U, Pföhler C, Krönig L, Ziemer M, Ugurel S
J Dtsch Dermatol Ges 2024 May;22(5):730-747. Epub 2024 Apr 28 doi: 10.1111/ddg.15405. PMID: 38679790
Dharwadkar P, Zaki TA, Murphy CC
Hematol Oncol Clin North Am 2022 Jun;36(3):449-470. Epub 2022 May 13 doi: 10.1016/j.hoc.2022.02.005. PMID: 35577711Free PMC Article
Shiraliyeva N, Friedrichs J, Buettner R, Friedrichs N
Pathol Res Pract 2017 Dec;213(12):1552-1555. Epub 2017 Sep 18 doi: 10.1016/j.prp.2017.09.012. PMID: 29033182
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article
Jasperson KW, Tuohy TM, Neklason DW, Burt RW
Gastroenterology 2010 Jun;138(6):2044-58. doi: 10.1053/j.gastro.2010.01.054. PMID: 20420945Free PMC Article

Clinical prediction guides

Shiraliyeva N, Friedrichs J, Buettner R, Friedrichs N
Pathol Res Pract 2017 Dec;213(12):1552-1555. Epub 2017 Sep 18 doi: 10.1016/j.prp.2017.09.012. PMID: 29033182
Chintalacheruvu LM, Shaw T, Buddam A, Diab O, Kassim T, Mukherjee S, Lynch HT
J Gastrointestin Liver Dis 2017 Jun;26(2):157-163. doi: 10.15403/jgld.2014.1121.262.maj. PMID: 28617886
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article
Lam AK, Chan SS, Leung M
World J Gastroenterol 2014 Jun 14;20(22):6815-20. doi: 10.3748/wjg.v20.i22.6815. PMID: 24944471Free PMC Article
Jasperson KW, Tuohy TM, Neklason DW, Burt RW
Gastroenterology 2010 Jun;138(6):2044-58. doi: 10.1053/j.gastro.2010.01.054. PMID: 20420945Free PMC Article

Recent systematic reviews

Mitric C, Salman L, Abrahamyan L, Kim SR, Pechlivanoglou P, Chan KKW, Gien LT, Ferguson SE
Gynecol Oncol 2023 Mar;170:133-142. Epub 2023 Jan 20 doi: 10.1016/j.ygyno.2022.12.008. PMID: 36682091
Eikenboom EL, Moen S, van Leeuwen L, Geurts-Giele WRR, Tops CMJ, van Ham TJ, Dinjens WNM, Dubbink HJ, Spaander MCW, Wagner A
HGG Adv 2023 Jan 12;4(1):100167. Epub 2022 Dec 14 doi: 10.1016/j.xhgg.2022.100167. PMID: 36624813Free PMC Article
Eikenboom EL, van der Werf-'t Lam AS, Rodríguez-Girondo M, Van Asperen CJ, Dinjens WNM, Hofstra RMW, Van Leerdam ME, Morreau H, Spaander MCW, Wagner A, Nielsen M
Clin Gastroenterol Hepatol 2022 Mar;20(3):e496-e507. Epub 2021 Apr 19 doi: 10.1016/j.cgh.2021.04.021. PMID: 33887476
Seppälä TT, Latchford A, Negoi I, Sampaio Soares A, Jimenez-Rodriguez R, Sánchez-Guillén L, Evans DG, Ryan N, Crosbie EJ, Dominguez-Valentin M, Burn J, Kloor M, Knebel Doeberitz MV, Duijnhoven FJBV, Quirke P, Sampson JR, Møller P, Möslein G; European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP)
Br J Surg 2021 May 27;108(5):484-498. doi: 10.1002/bjs.11902. PMID: 34043773Free PMC Article
Snowsill T, Coelho H, Huxley N, Jones-Hughes T, Briscoe S, Frayling IM, Hyde C
Health Technol Assess 2017 Sep;21(51):1-238. doi: 10.3310/hta21510. PMID: 28895526Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2021
      UK NICE Guideline NG151, Colorectal cancer, 2021
    • NICE, 2020
      UK NICE Diagnostics Guidance DG42, Testing strategies for Lynch syndrome in people with endometrial cancer, 2020
    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, MLH1, MSH2, MSH6, PMS2, EPCAM Pathogenic Variants, Lynch Syndrome (Hereditary Non-polyposis Colon Cancer [HNPCC]), 2019

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