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Colorectal cancer, hereditary nonpolyposis, type 2(HNPCC2; FCC2)

MedGen UID:
232603
Concept ID:
C1333991
Neoplastic Process
Synonyms: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; Hereditary non-polyposis colorectal cancer, type 2; Lynch syndrome II; 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

Suggested Reading

PubMed

PDQ Cancer Genetics Editorial Board
2002 PMID: 26389505
PDQ Cancer Genetics Editorial Board; PDQ Cancer Genetics Editorial Board
2002 PMID: 26389258
PDQ Cancer Genetics Editorial Board
2002 PMID: 26389210

External

AMA/NCHPEG, 2012

Recent clinical studies

Etiology

Atmar RL, Lyke KE, Deming ME, Jackson LA, Branche AR, El Sahly HM, Rostad CA, Martin JM, Johnston C, Rupp RE, Mulligan MJ, Brady RC, Frenck RW Jr, Bäcker M, Kottkamp AC, Babu TM, Rajakumar K, Edupuganti S, Dobrzynski D, Coler RN, Posavad CM, Archer JI, Crandon S, Nayak SU, Szydlo D, Zemanek JA, Dominguez Islas CP, Brown ER, Suthar MS, McElrath MJ, McDermott AB, O'Connell SE, Montefiori DC, Eaton A, Neuzil KM, Stephens DS, Roberts PC, Beigel JH; DMID 21-0012 Study Group
N Engl J Med 2022 Mar 17;386(11):1046-1057. Epub 2022 Jan 26 doi: 10.1056/NEJMoa2116414. PMID: 35081293Free PMC Article
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
Battaglin F, Naseem M, Lenz HJ, Salem ME
Clin Adv Hematol Oncol 2018 Nov;16(11):735-745. PMID: 30543589Free 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
Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousová M, Holubec L, Sturgeon C
Int J Cancer 2014 Jun 1;134(11):2513-22. Epub 2013 Aug 27 doi: 10.1002/ijc.28384. PMID: 23852704Free PMC Article

Diagnosis

Menahem B, Alves A, Regimbeau JM, Sabbagh C
J Visc Surg 2019 Dec;156(6):507-514. Epub 2019 Aug 21 doi: 10.1016/j.jviscsurg.2019.07.009. PMID: 31445799
Battaglin F, Naseem M, Lenz HJ, Salem ME
Clin Adv Hematol Oncol 2018 Nov;16(11):735-745. PMID: 30543589Free PMC Article
Oda K, Hamanishi J, Matsuo K, Hasegawa K
Gynecol Oncol 2018 Nov;151(2):381-389. Epub 2018 Sep 12 doi: 10.1016/j.ygyno.2018.09.001. PMID: 30217369Free PMC Article
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
Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousová M, Holubec L, Sturgeon C
Int J Cancer 2014 Jun 1;134(11):2513-22. Epub 2013 Aug 27 doi: 10.1002/ijc.28384. PMID: 23852704Free PMC Article

Therapy

Atmar RL, Lyke KE, Deming ME, Jackson LA, Branche AR, El Sahly HM, Rostad CA, Martin JM, Johnston C, Rupp RE, Mulligan MJ, Brady RC, Frenck RW Jr, Bäcker M, Kottkamp AC, Babu TM, Rajakumar K, Edupuganti S, Dobrzynski D, Coler RN, Posavad CM, Archer JI, Crandon S, Nayak SU, Szydlo D, Zemanek JA, Dominguez Islas CP, Brown ER, Suthar MS, McElrath MJ, McDermott AB, O'Connell SE, Montefiori DC, Eaton A, Neuzil KM, Stephens DS, Roberts PC, Beigel JH; DMID 21-0012 Study Group
N Engl J Med 2022 Mar 17;386(11):1046-1057. Epub 2022 Jan 26 doi: 10.1056/NEJMoa2116414. PMID: 35081293Free PMC Article
Araújo AN, Bugalho MJ
Horm Metab Res 2021 May;53(5):285-292. Epub 2021 May 7 doi: 10.1055/a-1453-0806. PMID: 33962475
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
Battaglin F, Naseem M, Lenz HJ, Salem ME
Clin Adv Hematol Oncol 2018 Nov;16(11):735-745. PMID: 30543589Free PMC Article
Oda K, Hamanishi J, Matsuo K, Hasegawa K
Gynecol Oncol 2018 Nov;151(2):381-389. Epub 2018 Sep 12 doi: 10.1016/j.ygyno.2018.09.001. PMID: 30217369Free PMC Article

Prognosis

Magrin L, Fanale D, Brando C, Fiorino A, Corsini LR, Sciacchitano R, Filorizzo C, Dimino A, Russo A, Bazan V
Oncogene 2021 Oct;40(40):5893-5901. Epub 2021 Aug 6 doi: 10.1038/s41388-021-01984-2. PMID: 34363023
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
Battaglin F, Naseem M, Lenz HJ, Salem ME
Clin Adv Hematol Oncol 2018 Nov;16(11):735-745. PMID: 30543589Free PMC Article
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

Clinical prediction guides

Araújo AN, Bugalho MJ
Horm Metab Res 2021 May;53(5):285-292. Epub 2021 May 7 doi: 10.1055/a-1453-0806. PMID: 33962475
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
Battaglin F, Naseem M, Lenz HJ, Salem ME
Clin Adv Hematol Oncol 2018 Nov;16(11):735-745. PMID: 30543589Free PMC Article
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

Recent systematic reviews

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
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
Win AK, Lindor NM, Jenkins MA
Breast Cancer Res 2013 Mar 19;15(2):R27. doi: 10.1186/bcr3405. PMID: 23510156Free PMC Article
Auranen A, Joutsiniemi T
Acta Obstet Gynecol Scand 2011 May;90(5):437-44. Epub 2011 Mar 16 doi: 10.1111/j.1600-0412.2011.01091.x. PMID: 21306348

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

    • 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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