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Hereditary Polyposis Syndromes

  • Genetics in Gastroenterology Practice (B Katona, Section Editor)
  • Published:
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Abstract

Purpose of Review

Colorectal cancer (CRC) is the third most common cancer in the USA and inherited cancer syndromes are responsible for approximately 3–5% of all CRCs. Genetic testing costs have plummeted in recent years; however, awareness and referral of high-risk patients for testing is still very low. We review the salient clinical features, genetics, and management of well-defined gastrointestinal (GI) hereditary polyposis syndromes including familial adenomatous polyposis, MUTYH-associated polyposis, and the hamartomatous polyposis syndromes.

Recent Findings

Comprehensive endoscopic surveillance has the potential to prevent the development of GI cancer and to identify early-stage cancer; newer developments like high-definition endoscopes, chromoendoscopy, and the use of cap-assisted endoscopy have shown promise for enhanced lesion detection rates. Several chemoprevention trials have yielded promising results but safety and efficacy data for long-term use is still awaited. Several new polyposis genes have also been identified in the recent years.

Summary

Multiple societies have recently published updated surveillance guidelines to aid clinicians in the detection and management of patients with hereditary GI polyposis syndromes. Although these syndromes are rare, it is crucial for the clinicians to recognize these in a timely manner, for the appropriate management plans for both the patient and their at risk family members.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:• Of importance ••Of major importance

  1. Wood ME, Kadlubek P, Pham TH, Wollins DS, Lu KH, Weitzel JN, et al. Quality of cancer family history and referral for genetic counseling and testing among oncology practices: a pilot test of quality measures as part of the American Society of Clinical Oncology Quality Oncology Practice Initiative. J Clin Oncol. 2014;32(8):824–9.

    Article  PubMed  PubMed Central  Google Scholar 

  2. National Comprehensive Cancer Network. Guidelines for genetic/familial high-risk assessment: colorectal https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf Version 2, 2019. Accessed July 12, 2019. *Concise NCCN guidelines on management of the hereditary cancer syndromes

  3. • Syngal S, Brand RE, Church JM, Giardello FM, Hampel HL, Burt RW. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223–62 Recent ACG guidelines on management of all hereditary GI syndromes.

    Article  Google Scholar 

  4. • van Leerdam ME, Roos VH, van Hooft JE, Dekker E, Jover R, Kaminski MF et al. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2019. Most recent guidelines from the ESGE.

  5. Kanth P, Grimmett J, Champine M, Burt R, Samadder NJ. Hereditary colorectal polyposis and cancer syndromes: a primer on diagnosis and management. Am J Gastroenterol. 2017;112(10):1509–25.

    Article  PubMed  Google Scholar 

  6. Ma H, Brosens LAA, Offerhaus GJA, Giardello FM, de Leng WWJ, Montgomery EA. Pathology and genetics of hereditary colorectal cancer. Pathology. 2018;50(1):49–59.

    Article  CAS  PubMed  Google Scholar 

  7. Talseth-Palmer BA. The genetic basis of colonic adenomatous polyposis syndromes. Hered Cancer Clin Pract. 2017;15:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Valle L, Vilar E, Tavtigian SV, Stoffel EM. Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine. J Pathol. 2017;247(5):574–88.

    Article  Google Scholar 

  9. Samadder NJ, Baffy N, Giridhar KV, Couch FJ, Riegert-Johnson D. Hereditary cancer syndromes-a primer on diagnosis and management, part 2: gastrointestinal cancer syndromes. Mayo Clin Proc. 2019;94(6):1099–116.

    Article  PubMed  Google Scholar 

  10. Burt RW, Leppert MF, Slattery ML, Samowitz WS, Spirio LN, Kerber RA, et al. Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology. 2004;127(2):444–51.

    Article  PubMed  Google Scholar 

  11. Soravia C, Berk T, Madlensky L, Mitri A, Cheng H, Gallinger S, et al. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet. 1998;62(6):1290–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Anaya DA, Chang GJ, Rodriguez-Bigas MA. Extracolonic manifestations of hereditary colorectal cancer syndromes. Clin Colon Rectal Surg. 2008;21(4):263–72.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Vasen HF, Moselin G, Alonso A, Aretz S, Bernstein I, Bertario L, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008;57(5):704–13.

    Article  CAS  PubMed  Google Scholar 

  14. Saurin JC, Napoleon B, Gay G. Ponchon, Arpurt JP, Boustiere C, et al. Endoscopic management of patients with familial adenomatous polyposis (FAP) following a colectomy. Endoscopy. 2005;37(50):499–501.

    Article  PubMed  Google Scholar 

  15. Smith JC, Schaffer MW, Ballard BR, Smoot DT, Herline AJ, Adunyah SE, et al. Adenocarcinomas after prophylactic surgery for familial adenomatous polyposis. J Cancer Ther. 2013;4(1):260–70.

    Article  PubMed  PubMed Central  Google Scholar 

  16. • Singh A, Steinhagen E, Katona BW. Approach to upper gastrointestinal tract lesions in familial adenomatous polyposis. Seminars Colon Rec Surg. 2018;29(3):102–7 Concise review on the approach to upper gastrointestinal lesions in FAP.

    Article  Google Scholar 

  17. Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989;2(8666):783–5.

    Article  CAS  PubMed  Google Scholar 

  18. • Thiruvengadam SS, Lopez R, O’Malley M, LaGuardia L, Church JM, Kalady M, et al. Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis. Gastrointest Endosc. 2019;89(2):345–354 e342 Recent database study showing that Spigelman stage alone does not predict duodenal cancer development.

    Article  PubMed  Google Scholar 

  19. • Hurley JJ, Thomas LE, Walton SJ, Thomas-Gibson S, Haycock A, Suzuki N, et al. The impact of chromoendoscopy for surveillance of the duodenum in patients with MUTYH-associated polyposis and familial adenomatous polyposis. Gastrointest Endosc. 2018;88(4):665–73 Recent study showing chromoendoscopy identifies polyps in FAP and MAP.

    Article  PubMed  Google Scholar 

  20. Worthley DL, Phillips KD, Wayte N, Schrader KA, Healey S, Kaurah P, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut. 2012;61(5):774–9.

    Article  CAS  PubMed  Google Scholar 

  21. Rudloff U. Gastric adenocarcinoma and proximal polyposis of the stomach: diagnosis and clinical perspectives. Clin Exp Gastroenterol. 2018;11:447–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. 1993;328(18):1313–6.

    Article  CAS  PubMed  Google Scholar 

  23. Winde G, Gumbinger HG, Osswald H, Kemper F, Bünte H. The NSAID sulindac reverses rectal adenomas in colectomized patients with familial adenomatous polyposis: clinical results of a dose-finding study on rectal sulindac administration. Int J Colorectal Dis. 1993;8(1):13–7.

    Article  CAS  PubMed  Google Scholar 

  24. Winde G, Schmid KW, Schlegel W, Fischer R, Osswald H, Bünte H. Complete reversion and prevention of rectal adenomas in colectomized patients with familial adenomatous polyposis by rectal low-dose sulindac maintenance treatment: advantages of a low-dose nonsteroidal anti-inflammatory drug regimen in reversing adenomas exceeding 33 months. Dis Colon Rectum. 1995;38(8):813–30.

    Article  CAS  PubMed  Google Scholar 

  25. Samadder NJ, Neklason DW, Boucher KM, Byrne KR, Kanth P, Samowitz W, et al. Effect of sulindac and erlotinib vs placebo on duodenal neoplasia in familial adenomatous polyposis: a randomized clinical trial. JAMA. 2016;315(12):1266–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nielsen M, Morreau H, Vasen HF, Hes FJ. MUTYH-associated polyposis (MAP). Crit Rev Oncol Hematol. 2011;79(1):1–16.

    Article  PubMed  Google Scholar 

  27. Mesiya S, Ancha HB, Ancha H, Lightfood S, Kida M, Guild R, et al. Sporadic colonic hamartomas in adults: a retrospective study. Gastrointest Endosc. 2005;62(6):886–91.

    Article  PubMed  Google Scholar 

  28. Ford MM. Hamartomotous polyposis syndromes: diagnosis and management. 2018; Seminars Colon Rec Surg. 29(3): 120-123

    Article  Google Scholar 

  29. Beggs AD, Latchford AR, Vasen HFA, Moslein G, Alonso A, Aretz S, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59(7):975–86.

    Article  CAS  PubMed  Google Scholar 

  30. Korsse SE, van Leerdam ME, Dekker E. Gastrointestinal diseases and their oro-dental manifestations: part 4: Peutz-Jeghers syndrome. Br Dent J. 2017;222(3):214–7.

    Article  CAS  PubMed  Google Scholar 

  31. van Lier MGF, Wagner A, Mathus-Vliegen EMH, Kuipers EJ, Steyerberg EW, van Leerdam ME. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105(6):1258–64 author reply 1265.

  32. Chiang J-M, Chen T-C. Clinical manifestations and STK11 germline mutations in Taiwanese patients with Peutz-Jeghers syndrome. Asian J Surg. 2018;41(5):480–5.

    Article  PubMed  Google Scholar 

  33. Latchford A, Cohen S, Auth M, Scaillon M, Viala J, Daniels R, et al. Management of Peutz-Jeghers syndrome in children and adolescents: a position paper from the ESPGHAN Polyposis Working Group. J Pediatr Gastroenterol Nutr. 2019;68(3):442–52.

    Article  PubMed  Google Scholar 

  34. Shaco-Levy R, Jasperson KW, Martin K, Samadder NJ, Burt RW, Ying J, et al. Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Hum Pathol. 2016;49:39–48.

    Article  PubMed  Google Scholar 

  35. Jelsig AM, Qvist N, Sunde L, Brusgaard K, Hansen T, Wikman FP, et al. Disease pattern in Danish patients with Peutz-Jeghers syndrome. Int J Colorectal Dis. 2016;31(5):997–1004.

    Article  CAS  PubMed  Google Scholar 

  36. Fostira F, Mollaki V, Lypas G, Alexandrakis G, Christianakis E, Tzouvala M, et al. Genetic analysis and clinical description of Greek patients with Peutz-Jeghers syndrome: creation of a national registry. Cancer Genet. 2018;220:19–23.

    Article  PubMed  Google Scholar 

  37. Chen H-Y, Jin X-W, Li B-R, Zhu M, Li J, Mao G-P, et al. Cancer risk in patients with Peutz-Jeghers syndrome: a retrospective cohort study of 336 cases. Tumour Biol. 2017;39(6):1010428317705131.

    PubMed  Google Scholar 

  38. van Lier MGF, Mathus-Vliegen EMH, Wagner A, van Leerdam ME, Kuipers EJ. High cumulative risk of intussusception in patients with Peutz-Jeghers syndrome: time to update surveillance guidelines? Am J Gastroenterol. 2011;106(5):940–5.

    Article  PubMed  Google Scholar 

  39. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119(6):1447–53.

    Article  CAS  PubMed  Google Scholar 

  40. Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJP, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006;12(10):3209–15.

    Article  CAS  PubMed  Google Scholar 

  41. Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley J-W, Kamel I, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62(3):339–47.

    Article  PubMed  Google Scholar 

  42. de Brabander J, Eskens FALM, Korsse SE, Dekker E, Dewint P, van Leerdam ME, et al. Chemoprevention in patients with Peutz-Jeghers syndrome: lessons learned. The Oncologist. 2018;23(4):399–e33.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Cohen S, Hyer W, Mas E, Auth M, Attard TM, Spalinger J, et al. Management of juvenile polyposis syndrome in children and adolescents: a position paper from the ESPGHAN Polyposis Working Group. J Pediatr Gastroenterol Nutr. 2019;68(3):453–62.

    Article  PubMed  Google Scholar 

  44. Latchford AR, Neale K, Phillips RKS, Clark SK. Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis Colon Rectum. 2012;55(10):1038–43.

    Article  PubMed  Google Scholar 

  45. Brosens LAA, van Hattem A, Hylind LM, Iacobuzio-Donahue C, Romans KE, Axilbund J, et al. Risk of colorectal cancer in juvenile polyposis. Gut. 2007;56(7):965–7.

    Article  PubMed  PubMed Central  Google Scholar 

  46. NCCN Clinical Practice Guidelines in Oncology; Genetic/familial high-risk assessment: breast and ovarian. Ver. 3.2019 [Internet]. [cited 2019 Jul 13]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf

  47. Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607–16.

    Article  CAS  PubMed  Google Scholar 

  48. Valle L, de Voer RM, Goldberg Y, Sjursen W, Forsti A, Ruiz-Ponte C, et al. Update on genetic predisposition to colorectal cancer and polyposis. Mol Aspects Med. 2019; in press

  49. Palles C, Cazier JB, Howarth KM, Domingo AM, Jones P, Broderick Z, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013;45(2):136–44.

    Article  CAS  PubMed  Google Scholar 

  50. Grolleman JE, de Voer RM, Elsayed FA, Nielsen M, Weren RD, Palles C, et al. Mutational signature analysis reveals NTHL1 deficiency to cause a multi-tumor phenotype. Cancer Cell. 2019;35(2):256–66.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Gastroenterology, City of Hope National Medical Center, Duarte, CA, USA

    Trilokesh D. Kidambi MD

  2. Division of Gastroenterology, Kansas City Veterans Affair Medical Center, Kansas City, MO, USA

    Divyanshoo R. Kohli MD

  3. Division of Gastroenterology and Hepatology, Department of Clinical Genomics, Mayo Clinic, Phoenix, AZ, USA

    N Jewel Samadder MD, MSc

  4. Division of Gastroenterology, University of California San Francisco, 505 Parnassus Ave, Room S357, San Francisco, CA, 941943, USA

    Aparajita Singh MD, MPH

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  1. Trilokesh D. Kidambi MD
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  3. N Jewel Samadder MD, MSc
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Correspondence to Aparajita Singh MD, MPH.

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Trilokesh D Kidambi, Divyanshoo R Kohli, N Jewel Samadder, and Aparajita Singh declare no conflict of interest.

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Trilokesh D. Kidambi and Divyanshoo R. Kohli are co-first authorship.

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Kidambi, T.D., Kohli, D.R., Samadder, N.J. et al. Hereditary Polyposis Syndromes. Curr Treat Options Gastro 17, 650–665 (2019). https://doi.org/10.1007/s11938-019-00251-4

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