MUT Y Homolog (MUTYH)-Associated Polyposis (MAP)

Raphael Moore, MD
The Operative Review of Surgery. 2023; 1:122-125.

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Table of Contents

Pathophysiology and Presentation
Diagnosis and Management

Other Colorectal Cancer and Polyposis Syndromes
References

Pathophysiology and Presentation

Pathophysiology

  • Mutation in MUT Y Homolog (MUTYH) Gene 1
    • Formerly Called the MYH Gene
  • Autosomal Recessive 1

Presentation

  • Characterized by 10-100’s of Colorectal Adenomatous Polyps 2
    • Can Also Develop Hyperplastic and Mixed Polyps 2
    • Often Right-Side Predominant (29-69%) 3-5
  • Risk or Colorectal Cancer:
    • 43-63% by Age 60 2
    • 80-90% Lifetime without Timely Surveillance 6,7

Extracolonic Manifestations 2

  • Duodenal Polyps (17-34%)
    • Duodenal Cancer (4%)
  • Gastric Polyps (11%)
    • Gastric Cancer (1% – Not Significantly Higher Than the General Population)
  • Bladder Cancer
    • 6-8% in Females
    • 6-25% in Males
  • Ovarian Cancer (6-14%)
  • Endometrial Cancer (3%)
  • Breast Cancer (12-25%)
  • Unclear Associations:
    • Thyroid Cancer
    • Desmoid Tumors
    • Pancreatic Cancer
    • Epidermoid Cysts

Diagnosis and Management

Diagnosis

  • Diagnosis Confirmed by Genetic Testing

Screening/Surveillance 8

  • Colonoscopy Every 1-2 Years, Starting at Age 25-30 Years
    • May Consider Starting Earlier at Age 18-20 Years 9,10
  • Upper Endoscopy Every 3-24 Months, Starting at Age 30-35 Years
  • Annual Physical Exam and Thyroid Ultrasound

Indications for Colectomy 8

  • Absolute Indications (2015 ACG Guidelines):
    • Documented or Suspected Colorectal Cancer
    • Significant Symptoms
  • Relative Indications (2015 ACG Guidelines):
    • Multiple Large Adenomas > 6 mm
    • Significant Increase in Adenoma Number on Consecutive Exams
    • Adenoma with High-Grade Dysplasia
    • Inability to Adequately Survey the Colon Because of Multiple Diminutive Polyps
  • Prophylactic Colectomy Generally Not Indicated

Other Colorectal Cancer and Polyposis Syndromes

Syndromes

  • Familial Adenomatous Polyposis (FAP)
  • Lynch Syndrome
  • Juvenile Polyposis Syndrome (JPS)/Familial Juvenile Polyposis
  • MUT Y Homolog (MUTYH)-Associated Polyposis (MAP)
  • Peutz-Jeghers Syndrome (PJS)
  • Serrated Polyposis Syndrome (SPS)
  • PTEN Hamartoma Tumor Syndromes: (PHTS)

Comparisons

References

  1. MUTYH-Associated Polyposis. National Cancer Institute. NIH.
  2. Nielsen M, Infante E, Brand R. MUTYH 2012 Oct 4 [updated 2021 May 27]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews
  3. Lipton L, Halford SE, Johnson V, Novelli M, Jones A, Cummings C, Barclay E, Sieber O, Sadat A, Bisgaard M, Hodgson S, Aaltonen L, Thomas H, Tomlinson I. Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. Cancer Res. 2003;63:7595–9.
  4. O’Shea AM, Cleary SP, Croitoru MA, Kim H, Berk T, Monga N, Riddell RH, Pollett A, Gallinger S. Pathological features of colorectal carcinomas in MYH-associated polyposis. Histopathology. 2008;53:184–94.
  5. Nielsen M, de Miranda NF, van Puijenbroek M, Jordanova ES, Middeldorp A, van Wezel T, van Eijk R, Tops CM, Vasen HF, Hes FJ, Morreau H. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas. BMC Cancer. 2009a;9:184.
  6. Lubbe SJ, Di Bernardo MC, Chandler IP, Houlston RS. Clinical implications of the colorectal cancer risk associated with MUTYH mutation. J Clin Oncol. 2009;27:3975–80.
  7. Win AK, Dowty JG, Cleary SP, Kim H, Buchanan DD, Young JP, Clendenning M, Rosty C, MacInnis RJ, Giles GG, Boussioutas A, Macrae FA, Parry S, Goldblatt J, Baron JA, Burnett T, Le Marchand L, Newcomb PA, Haile RW, Hopper JL, Cotterchio M, Gallinger S, Lindor NM, Tucker KM, Winship IM, Jenkins MA. Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology. 2014;146:1208-11.e1-5.
  8. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 Feb;110(2):223-62; quiz 263.
  9. Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, Tomlinson I, Thomas HJW, Hill J; Hereditary CRC guidelines eDelphi consensus group. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut. 2020 Mar;69(3):411-444.
  10. Yang J, Gurudu SR, Koptiuch C, Agrawal D, Buxbaum JL, Abbas Fehmi SM, Fishman DS, Khashab MA, Jamil LH, Jue TL, Law JK, Lee JK, Naveed M, Qumseya BJ, Sawhney MS, Thosani N, Wani SB, Samadder NJ. American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in familial adenomatous polyposis syndromes. Gastrointest Endosc. 2020 May;91(5):963-982.e2.