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Lynch syndrome

MedGen UID:
1633554
•Concept ID:
C4552100
•
Disease or Syndrome
Synonyms: Lynch Syndrome; Syndrome, Lynch
SNOMED CT: Lynch syndrome (716318002)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (Orphanet)
 
Genes (locations): MLH1 (3p22.2); MSH2 (2p21-16.3); MSH6 (2p16.3); PMS2 (7p22.1)
 
Monarch Initiative: MONDO:0005835
Orphanet: ORPHA144

Disease characteristics

Excerpted from the GeneReview: Lynch Syndrome
Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, ovary, stomach, small bowel, urinary tract, biliary tract, brain (usually glioblastoma), skin (sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas), pancreas, and prostate. Cancer risks and age of onset vary depending on the associated gene. Several other cancer types have been reported to occur in individuals with Lynch syndrome (e.g., breast, sarcomas, adrenocortical carcinoma). However, the data are not sufficient to demonstrate that the risk of developing these cancers is increased in individuals with Lynch syndrome. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Gregory Idos  |  Laura Valle   view full author information

Professional guidelines

PubMed

Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.
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
Mucinous colorectal adenocarcinoma: clinical pathology and treatment options.
Luo C, Cen S, Ding G, Wu W
Cancer Commun (Lond) 2019 Mar 29;39(1):13. doi: 10.1186/s40880-019-0361-0. PMID: 30922401Free PMC Article
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article

Curated

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer, 2024

UK NICE Guideline NG151, Colorectal cancer, 2021

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

Society of Gynecologic Oncology (SGO) Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer

American College of Medical Genetics and Genomics Family History ACT Sheet, Colon Cancer (Asymptomatic), 2012

Suggested Reading

PubMed

Lynch Syndrome in Urologic Malignancies - What Does the Urologist Need to Know?
Goldberg H, Wallis CJD, Klaassen Z, Chandrasekar T, Fleshner N, Zlotta AR
Urology 2019 Dec;134:24-31. Epub 2019 Jul 11 doi: 10.1016/j.urology.2019.07.004. PMID: 31302137
Genetics of Colorectal Cancer (PDQ®): Health Professional Version.
PDQ Cancer Genetics Editorial Board
2002 PMID: 26389505
Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.
PDQ Cancer Genetics Editorial Board
2002 PMID: 26389258
Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.
PDQ Cancer Genetics Editorial Board
2002 PMID: 26389210

External

AMA/NCHPEG, 2012

Recent clinical studies

Etiology

Identification of Lynch Syndrome.
Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Lynch Syndrome and MSI-H Cancers: From Mechanisms to "Off-The-Shelf" Cancer Vaccines.
Roudko V, Cimen Bozkus C, Greenbaum B, Lucas A, Samstein R, Bhardwaj N
Front Immunol 2021;12:757804. Epub 2021 Sep 24 doi: 10.3389/fimmu.2021.757804. PMID: 34630437Free PMC Article
Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.
Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO
Am J Hum Genet 2021 Jan 7;108(1):163-175. Epub 2020 Dec 23 doi: 10.1016/j.ajhg.2020.12.003. PMID: 33357406Free PMC Article
Molecular pathology of Lynch syndrome.
Cerretelli G, Ager A, Arends MJ, Frayling IM
J Pathol 2020 Apr;250(5):518-531. doi: 10.1002/path.5422. PMID: 32141610
Recent advances in Lynch syndrome.
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

Diagnosis

Lynch Syndrome Genetics and Clinical Implications.
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
Mismatch repair deficiency: The what, how and why it is important.
Olave MC, Graham RP
Genes Chromosomes Cancer 2022 Jun;61(6):314-321. Epub 2021 Dec 9 doi: 10.1002/gcc.23015. PMID: 34837268
Identification of Lynch Syndrome.
Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Endometrial cancer in Lynch syndrome.
Zhao S, Chen L, Zang Y, Liu W, Liu S, Teng F, Xue F, Wang Y
Int J Cancer 2022 Jan 1;150(1):7-17. Epub 2021 Sep 9 doi: 10.1002/ijc.33763. PMID: 34398969
Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention.
Yurgelun MB, Hampel H
Am Soc Clin Oncol Educ Book 2018 May 23;38:101-109. doi: 10.1200/EDBK_208341. PMID: 30231390

Therapy

Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment.
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
Targeted Therapy for Colorectal Cancer.
Sakata S, Larson DW
Surg Oncol Clin N Am 2022 Apr;31(2):255-264. Epub 2022 Mar 9 doi: 10.1016/j.soc.2021.11.006. PMID: 35351276
Lynch Syndrome and MSI-H Cancers: From Mechanisms to "Off-The-Shelf" Cancer Vaccines.
Roudko V, Cimen Bozkus C, Greenbaum B, Lucas A, Samstein R, Bhardwaj N
Front Immunol 2021;12:757804. Epub 2021 Sep 24 doi: 10.3389/fimmu.2021.757804. PMID: 34630437Free PMC Article
Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.
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
Recent advances in Lynch syndrome.
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

Prognosis

Mismatch repair deficiency: The what, how and why it is important.
Olave MC, Graham RP
Genes Chromosomes Cancer 2022 Jun;61(6):314-321. Epub 2021 Dec 9 doi: 10.1002/gcc.23015. PMID: 34837268
Identification of Lynch Syndrome.
Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Mucinous colorectal adenocarcinoma: clinical pathology and treatment options.
Luo C, Cen S, Ding G, Wu W
Cancer Commun (Lond) 2019 Mar 29;39(1):13. doi: 10.1186/s40880-019-0361-0. PMID: 30922401Free PMC Article
Microsatellite instability in colorectal cancer.
De' Angelis GL, Bottarelli L, Azzoni C, De' Angelis N, Leandro G, Di Mario F, Gaiani F, Negri F
Acta Biomed 2018 Dec 17;89(9-S):97-101. doi: 10.23750/abm.v89i9-S.7960. PMID: 30561401Free PMC Article
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.
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

Clinical prediction guides

Overview of the 2022 WHO Classification of Adrenal Cortical Tumors.
Mete O, Erickson LA, Juhlin CC, de Krijger RR, Sasano H, Volante M, Papotti MG
Endocr Pathol 2022 Mar;33(1):155-196. Epub 2022 Mar 14 doi: 10.1007/s12022-022-09710-8. PMID: 35288842Free PMC Article
Mismatch repair deficiency: The what, how and why it is important.
Olave MC, Graham RP
Genes Chromosomes Cancer 2022 Jun;61(6):314-321. Epub 2021 Dec 9 doi: 10.1002/gcc.23015. PMID: 34837268
Identification of Lynch Syndrome.
Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.
Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO
Am J Hum Genet 2021 Jan 7;108(1):163-175. Epub 2020 Dec 23 doi: 10.1016/j.ajhg.2020.12.003. PMID: 33357406Free PMC Article
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.
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

Recent systematic reviews

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender.
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
ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach.
Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, Miller R, Riaz N, Douillard JY, Andre F, Scarpa A
Ann Oncol 2019 Aug 1;30(8):1232-1243. doi: 10.1093/annonc/mdz116. PMID: 31056702
Risk of metachronous colorectal cancer following colectomy in Lynch syndrome: a systematic review and meta-analysis.
Anele CC, Adegbola SO, Askari A, Rajendran A, Clark SK, Latchford A, Faiz OD
Colorectal Dis 2017 Jun;19(6):528-536. doi: 10.1111/codi.13679. PMID: 28407411
Ovarian cancer in Lynch syndrome; a systematic review.
Helder-Woolderink JM, Blok EA, Vasen HF, Hollema H, Mourits MJ, De Bock GH
Eur J Cancer 2016 Mar;55:65-73. Epub 2016 Jan 13 doi: 10.1016/j.ejca.2015.12.005. PMID: 26773421
Peutz-Jeghers syndrome: a systematic review and recommendations for management.
Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bülow S, Burn J, Capella G, Colas C, Friedl W, Møller P, Hes FJ, Järvinen H, Mecklin JP, Nagengast FM, Parc Y, Phillips RK, Hyer W, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen JT, Clark SK, Hodgson SV
Gut 2010 Jul;59(7):975-86. doi: 10.1136/gut.2009.198499. PMID: 20581245

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
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    • 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

    • NCCN, 2024
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer, 2024
    • 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
    • SGO, 2014
      Society of Gynecologic Oncology (SGO) Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer
    • ACMG ACT, 2012
      American College of Medical Genetics and Genomics Family History ACT Sheet, Colon Cancer (Asymptomatic), 2012

    Reviews

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