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Lynch syndrome 1(FCC1; HNPCC1; LYNCH1)

MedGen UID:
423615
Concept ID:
C2936783
Disease or Syndrome
Synonyms: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; Colorectal cancer, hereditary, nonpolyposis, type 1; Hereditary non-polyposis colorectal cancer, type 1; Lynch syndrome I; MSH2-Related Hereditary Non-Polyposis Colon Cancer; MSH2-Related Lynch Syndrome
 
Genes (locations): MSH2 (2p21-16.3); PMS1 (2q32.2)
 
Monarch Initiative: MONDO:0007356
OMIM®: 120435

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 descriptions

From OMIM
Lynch syndrome (LYNCH), also called hereditary nonpolyposis colorectal cancer, is defined as an autosomal dominant predisposition to a spectrum of cancers, primarily of the colorectum and endometrium, which exhibit impaired DNA mismatch repair (MMR) activity (summary by Lynch et al., 2015).  http://www.omim.org/entry/120435
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  
  • CROGVLynch syndrome 1

Professional guidelines

PubMed

Gallon R, Phelps R, Hayes C, Brugieres L, Guerrini-Rousseau L, Colas C, Muleris M, Ryan NAJ, Evans DG, Grice H, Jessop E, Kunzemann-Martinez A, Marshall L, Schamschula E, Oberhuber K, Azizi AA, Baris Feldman H, Beilken A, Brauer N, Brozou T, Dahan K, Demirsoy U, Florkin B, Foulkes W, Januszkiewicz-Lewandowska D, Jones KJ, Kratz CP, Lobitz S, Meade J, Nathrath M, Pander HJ, Perne C, Ragab I, Ripperger T, Rosenbaum T, Rueda D, Sarosiek T, Sehested A, Spier I, Suerink M, Zimmermann SY, Zschocke J, Borthwick GM, Wimmer K, Burn J, Jackson MS, Santibanez-Koref M
Gastroenterology 2023 Apr;164(4):579-592.e8. Epub 2022 Dec 29 doi: 10.1053/j.gastro.2022.12.017. PMID: 36586540
Resnick K, Straughn JM Jr, Backes F, Hampel H, Matthews KS, Cohn DE
Obstet Gynecol 2009 Sep;114(3):530-536. doi: 10.1097/AOG.0b013e3181b11ecc. PMID: 19701031

Curated

Rahner N, Steinke V, Schlegelberger B, Olschwang S, Eisinger F, Hutter P
Eur J Hum Genet 2010 Sep;18(9) Epub 2010 Jan 27 doi: 10.1038/ejhg.2009.232. PMID: 20104243Free PMC Article

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

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

Pearlman R, Markow M, Knight D, Chen W, Arnold CA, Pritchard CC, Hampel H, Frankel WL
Mod Pathol 2018 Dec;31(12):1891-1900. Epub 2018 Jul 2 doi: 10.1038/s41379-018-0058-y. PMID: 29967423Free PMC Article
Kerr L, Rewhorn MJ, Longmuir M, Fraser S, Walsh S, Andrew N, Leung HY
BMC Cancer 2016 Jul 25;16:529. doi: 10.1186/s12885-016-2573-x. PMID: 27456091Free PMC Article
Bremers AJ, van Laarhoven KJ, van der Kolk BM, de Wilt JH, van Goor H
Br J Surg 2013 Mar;100(4):568-71. Epub 2012 Nov 27 doi: 10.1002/bjs.9005. PMID: 23188592
Resnick K, Straughn JM Jr, Backes F, Hampel H, Matthews KS, Cohn DE
Obstet Gynecol 2009 Sep;114(3):530-536. doi: 10.1097/AOG.0b013e3181b11ecc. PMID: 19701031
Rex DK
Am J Gastroenterol 1995 Mar;90(3):353-65. PMID: 7872270

Diagnosis

Pearlman R, Markow M, Knight D, Chen W, Arnold CA, Pritchard CC, Hampel H, Frankel WL
Mod Pathol 2018 Dec;31(12):1891-1900. Epub 2018 Jul 2 doi: 10.1038/s41379-018-0058-y. PMID: 29967423Free PMC Article
Kerr L, Rewhorn MJ, Longmuir M, Fraser S, Walsh S, Andrew N, Leung HY
BMC Cancer 2016 Jul 25;16:529. doi: 10.1186/s12885-016-2573-x. PMID: 27456091Free PMC Article
Resnick K, Straughn JM Jr, Backes F, Hampel H, Matthews KS, Cohn DE
Obstet Gynecol 2009 Sep;114(3):530-536. doi: 10.1097/AOG.0b013e3181b11ecc. PMID: 19701031
Kwon JS, Sun CC, Peterson SK, White KG, Daniels MS, Boyd-Rogers SG, Lu KH
Cancer 2008 Jul 15;113(2):326-35. doi: 10.1002/cncr.23554. PMID: 18506736
Rex DK
Am J Gastroenterol 1995 Mar;90(3):353-65. PMID: 7872270

Prognosis

Resnick K, Straughn JM Jr, Backes F, Hampel H, Matthews KS, Cohn DE
Obstet Gynecol 2009 Sep;114(3):530-536. doi: 10.1097/AOG.0b013e3181b11ecc. PMID: 19701031
Rex DK
Am J Gastroenterol 1995 Mar;90(3):353-65. PMID: 7872270

Clinical prediction guides

Resnick K, Straughn JM Jr, Backes F, Hampel H, Matthews KS, Cohn DE
Obstet Gynecol 2009 Sep;114(3):530-536. doi: 10.1097/AOG.0b013e3181b11ecc. PMID: 19701031
Rex DK
Am J Gastroenterol 1995 Mar;90(3):353-65. PMID: 7872270

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, 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
    • 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
    • EuroGenetest, 2010
      Clinical utility gene card for: Lynch syndrome (MLH1, MSH2, MSH6, PMS2)

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