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Colorectal cancer, hereditary nonpolyposis, type 2(LYNCH2)

MedGen UID:
232603
Concept ID:
C1333991
Disease or Syndrome
Synonyms: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; Hereditary non-polyposis colorectal cancer, type 2; Lynch syndrome II; LYNCH2; MLH1-Related Lynch Syndrome
 
Gene (location): MLH1 (3p22.2)
 
Monarch Initiative: MONDO:0012249
OMIM®: 609310

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]
Authors:
Gregory Idos  |  Laura Valle   view full author information

Additional description

From MedlinePlus Genetics
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.

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.  https://medlineplus.gov/genetics/condition/lynch-syndrome

Clinical features

From HPO
Colon cancer
MedGen UID:
2839
Concept ID:
C0007102
Neoplastic Process
A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVColorectal cancer, hereditary nonpolyposis, type 2

Professional guidelines

PubMed

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
Gallon R, Kibbi N, Cook S, Santibanez-Koref M, Jackson MS, Burn J, Rajan N
Br J Dermatol 2021 Nov;185(5):1045-1046. Epub 2021 Jul 22 doi: 10.1111/bjd.20522. PMID: 34050928Free PMC Article
Grzymski JJ, Elhanan G, Morales Rosado JA, Smith E, Schlauch KA, Read R, Rowan C, Slotnick N, Dabe S, Metcalf WJ, Lipp B, Reed H, Sharma L, Levin E, Kao J, Rashkin M, Bowes J, Dunaway K, Slonim A, Washington N, Ferber M, Bolze A, Lu JT
Nat Med 2020 Aug;26(8):1235-1239. Epub 2020 Jul 27 doi: 10.1038/s41591-020-0982-5. PMID: 32719484

Curated

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

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

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

Recent clinical studies

Etiology

Wang Q, Leclerc J, Bougeard G, Olschwang S, Vasseur S, Cassinari K, Boidin D, Lefol C, Naïbo P, Frébourg T, Buisine MP, Baert-Desurmont S; French Consortium of Oncogenetic laboratories for colorectal cancers, Unicancer Cancer Genetic Group (GGC)
J Med Genet 2020 Jul;57(7):487-499. Epub 2020 Jan 28 doi: 10.1136/jmedgenet-2019-106256. PMID: 31992580
Flux K
Surg Pathol Clin 2017 Jun;10(2):367-382. doi: 10.1016/j.path.2017.01.009. PMID: 28477886
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
Aparicio T, Zaanan A, Mary F, Afchain P, Manfredi S, Evans TR
Gastroenterol Clin North Am 2016 Sep;45(3):447-57. doi: 10.1016/j.gtc.2016.04.004. PMID: 27546842
Roberts ME, Riegert-Johnson DL, Thomas BC, Rumilla KM, Thomas CS, Heckman MG, Purcell JU, Hanson NB, Leppig KA, Lim J, Cappel MA
Genet Med 2014 Sep;16(9):711-6. Epub 2014 Mar 6 doi: 10.1038/gim.2014.19. PMID: 24603434

Diagnosis

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
Wang Q, Leclerc J, Bougeard G, Olschwang S, Vasseur S, Cassinari K, Boidin D, Lefol C, Naïbo P, Frébourg T, Buisine MP, Baert-Desurmont S; French Consortium of Oncogenetic laboratories for colorectal cancers, Unicancer Cancer Genetic Group (GGC)
J Med Genet 2020 Jul;57(7):487-499. Epub 2020 Jan 28 doi: 10.1136/jmedgenet-2019-106256. PMID: 31992580
Flux K
Surg Pathol Clin 2017 Jun;10(2):367-382. doi: 10.1016/j.path.2017.01.009. PMID: 28477886
Aparicio T, Zaanan A, Mary F, Afchain P, Manfredi S, Evans TR
Gastroenterol Clin North Am 2016 Sep;45(3):447-57. doi: 10.1016/j.gtc.2016.04.004. PMID: 27546842
Roberts ME, Riegert-Johnson DL, Thomas BC, Rumilla KM, Thomas CS, Heckman MG, Purcell JU, Hanson NB, Leppig KA, Lim J, Cappel MA
Genet Med 2014 Sep;16(9):711-6. Epub 2014 Mar 6 doi: 10.1038/gim.2014.19. PMID: 24603434

Therapy

Aparicio T, Zaanan A, Mary F, Afchain P, Manfredi S, Evans TR
Gastroenterol Clin North Am 2016 Sep;45(3):447-57. doi: 10.1016/j.gtc.2016.04.004. PMID: 27546842
Kyllo RL, Brady KL, Hurst EA
Dermatol Surg 2015 Jan;41(1):1-15. doi: 10.1097/DSS.0000000000000152. PMID: 25521100
Buecher B, Cacheux W, Rouleau E, Dieumegard B, Mitry E, Lièvre A
Dig Liver Dis 2013 Jun;45(6):441-9. Epub 2012 Nov 26 doi: 10.1016/j.dld.2012.10.006. PMID: 23195666
Hunn J, Rodriguez GC
Clin Obstet Gynecol 2012 Mar;55(1):3-23. doi: 10.1097/GRF.0b013e31824b4611. PMID: 22343225
Hopfner R
Curr Opin Investig Drugs 2002 Feb;3(2):246-51. PMID: 12020054

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
Léon-Castillo A
Int J Gynecol Cancer 2023 Mar 6;33(3):333-342. doi: 10.1136/ijgc-2022-003772. PMID: 36878561
Wang Q, Leclerc J, Bougeard G, Olschwang S, Vasseur S, Cassinari K, Boidin D, Lefol C, Naïbo P, Frébourg T, Buisine MP, Baert-Desurmont S; French Consortium of Oncogenetic laboratories for colorectal cancers, Unicancer Cancer Genetic Group (GGC)
J Med Genet 2020 Jul;57(7):487-499. Epub 2020 Jan 28 doi: 10.1136/jmedgenet-2019-106256. PMID: 31992580
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
Roberts ME, Riegert-Johnson DL, Thomas BC, Rumilla KM, Thomas CS, Heckman MG, Purcell JU, Hanson NB, Leppig KA, Lim J, Cappel MA
Genet Med 2014 Sep;16(9):711-6. Epub 2014 Mar 6 doi: 10.1038/gim.2014.19. PMID: 24603434

Clinical prediction guides

Wang Q, Leclerc J, Bougeard G, Olschwang S, Vasseur S, Cassinari K, Boidin D, Lefol C, Naïbo P, Frébourg T, Buisine MP, Baert-Desurmont S; French Consortium of Oncogenetic laboratories for colorectal cancers, Unicancer Cancer Genetic Group (GGC)
J Med Genet 2020 Jul;57(7):487-499. Epub 2020 Jan 28 doi: 10.1136/jmedgenet-2019-106256. PMID: 31992580
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
Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, Boyd N, Pike J, Anglesio M, Kwon JS, Karnezis AN, Huntsman DG, Gilks CB, McAlpine JN
Cancer 2017 Mar 1;123(5):802-813. Epub 2017 Jan 6 doi: 10.1002/cncr.30496. PMID: 28061006
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
Buecher B, Cacheux W, Rouleau E, Dieumegard B, Mitry E, Lièvre A
Dig Liver Dis 2013 Jun;45(6):441-9. Epub 2012 Nov 26 doi: 10.1016/j.dld.2012.10.006. PMID: 23195666

Recent systematic reviews

Aziz S, O'Sullivan H, Heelan K, Alam A, McVeigh TP
Fam Cancer 2023 Apr;22(2):167-175. Epub 2022 Nov 23 doi: 10.1007/s10689-022-00319-8. PMID: 36418753Free PMC Article
Toh JWT, Phan K, Reza F, Chapuis P, Spring KJ
Int J Colorectal Dis 2021 Aug;36(8):1573-1596. Epub 2021 Feb 18 doi: 10.1007/s00384-021-03874-1. PMID: 33604737
Cattelan L, Abi-Rafeh J, Brimo F, Kazan R, Redpath M, Chergui M
Am J Dermatopathol 2020 Sep;42(9):700-705. doi: 10.1097/DAD.0000000000001633. PMID: 32568842
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
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

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

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

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