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Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
Jan 10, 2025;

Genetic predisposition to polyposis syndromes.

Natalia García-Simón, Fátima Valentín, Atocha Romero
Author Information
  1. Natalia García-Simón: Hereditary Cancer Unit, Medical Oncology Department, Puerta de Hierro University Hospital, Majadahonda, 28222, Madrid, Spain. ORCID
  2. Fátima Valentín: Gastroenterology Department, Biomedical Research Institute (IDIPHISA), Puerta de Hierro University Hospital, Majadahonda, 28222, Madrid, Spain.
  3. Atocha Romero: Hereditary Cancer Unit, Medical Oncology Department, Puerta de Hierro University Hospital, Majadahonda, 28222, Madrid, Spain. atocha10@hotmail.com. ORCID
PMID: 39794684 DOI: 10.1007/s12094-024-03825-6

Abstract

Hereditary polyposis syndromes are significant contributors to colorectal cancer (CRC). These syndromes are characterized by the development of various types and numbers of polyps, distinct inheritance patterns, and extracolonic manifestations. This review explores these syndromes with a focus on their genetic characteristics. Advances in diagnostics, particularly the identification of pathogenic germline variants through massive sequencing technologies, have enhanced our understanding of the genetic alterations associated with polyp formation and CRC risk. Identifying pathogenic variants beyond traditional diagnostic criteria improves the management and surveillance of these syndromes. Genetic diagnosis not only refines patient treatment and surveillance, but also informs relatives of potential risks, enabling appropriate management. However, challenges persist in determining the pathogenicity of newly discovered mutations due to their low prevalence. This review covers hereditary polyposis syndromes, from well-established to newly recognized types, providing insights into their genetic landscapes and highlighting the need for tailored surveillance based on genotype.

Keywords

Adenomatous polyposis Genetic testing Hamartomatous polyposis Hereditary polyposis syndromes Serrated polyposis

References

  1. Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, et al. Global cancer observatory: cancer today (version 1.1). Lyon, France: International Agency for Research on Cancer. 2024. https://gco.iarc.who.int/today . Accessed 26 May 2024
  2. Basso G, Bianchi P, Malesci A, Laghi L. Hereditary or sporadic polyposis syndromes. Best Pract Res Clin Gastroenterol. 2017;31:409–17. [PMID: 28842050]
  3. Kidambi TD, Kohli DR, Samadder NJ, Singh A. Hereditary polyposis syndromes. Curr Treat Options Gastroenterol. 2019;17:650–65. [PMID: 31705372]
  4. Chen L, Ye L, Hu B. Hereditary colorectal cancer syndromes: molecular genetics and precision medicine. Biomedicines. 2022;10:3207. [PMID: 36551963]
  5. 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;110:223–62. [PMID: 25645574]
  6. Pyrtel K. Genetic testing for polyposis syndromes. Clin Colon Rectal Surg. 2016;29:345–52. [PMID: 31777466]
  7. Jelsig AM, Byrjalsen A, Busk Madsen M, Kuhlmann TP, van Overeem HT, Wadt KAW, et al. Novel genetic causes of gastrointestinal polyposis syndromes. Appl Clin Genet. 2021;14:455–66. [PMID: 34866929]
  8. Valle L, de Voer RM, Goldberg Y, Sjursen W, Försti A, Ruiz-Ponte C, et al. Update on genetic predisposition to colorectal cancer and polyposis. Mol Aspects Med. 2019;69:10–26. [PMID: 30862463]
  9. Tung N, Ricker C, Messersmith H, Balmaña J, Domchek S, Stoffel EM, et al. Selection of germline genetic testing panels in patients with cancer: ASCO guideline. J Clin Oncol. 2024;42:2599–615. [PMID: 38759122]
  10. Richards R, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24. [PMID: 25741868]
  11. ENIGMA Consortium. ENIGMA classification criteria [Online]. 2023. https://enigmaconsortium.org/enigma-classification-criteria/ . Accessed 23 Novembre 2024.
  12. Garrett A, Alle S, Loong L, Durkie M, Drummond J, Burghel GJ, et al. CanVIG-UK consensus specification for cancer susceptibility genes (CSGs) of ACGS best practice guidelines for variant classification (v2.2019)
  13. 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;51:877–95. [PMID: 31342472]
  14. Hampel H, Kalady MF, Pearlman R, Stanich PP. Hereditary colorectal cancer. Hematol Oncol Clin North Am. 2022;36:429–47. [PMID: 35577708]
  15. Hayat R, Manzoor M, Hussain A. Wnt signaling pathway: a comprehensive review. Cell Biol Int. 2022;46:863–77. [PMID: 35297539]
  16. Benchabane H, Ahmed Y. The adenomatous polyposis coli tumor suppressor and Wnt signaling in the regulation of apoptosis. Adv Exp Med Biol. 2009;656:75–84. [PMID: 19928354]
  17. PDQ Cancer Genetics Editorial Board. Genetics of colorectal cancer (PDQ®): health professional version. 2024 Feb 2. In: PDQ cancer information summaries [Internet]. National Cancer Institute (US), Bethesda (MD). 2002.
  18. Stjepanovic N, Moreira L, Carneiro F, Balaguer F, CervantesBalmaña AJ, ESMO Guidelines Committee, et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:1558–71. [PMID: 31378807]
  19. 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. 2019;247:574–88. [PMID: 30584801]
  20. Rebuzzi F, Ulivi P, Tedaldi G. Genetic predisposition to colorectal cancer: how many and which genes to test? Int J Mol Sci. 2023;24:2137. [PMID: 36768460]
  21. Nagase H, Nakamura Y. Mutations of the APC (adenomatous polyposis coli) gene. Hum Mutat. 1993;2:425–34. [PMID: 8111410]
  22. Su LK, Kohlmann W, Ward PA, Lynch PM. Different familial adenomatous polyposis phenotypes resulting from deletions of the entire APC exon 15. Hum Genet. 2002;111:88–95. [PMID: 12136240]
  23. Dodaro C, Grifasi C, Florio J, Santangelo ML, Duraturo F, De Rosa M, et al. The role of mutation analysis of the APC gene in the management of FAP patients. A controversial issue. Ann Ital Chir. 2016;87:321–5. [PMID: 27682830]
  24. Yen T, Stanich PP, Axell L, Patel SG. APC-Associated Polyposis Conditions. 1998 Dec 18 [updated 2022 May 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Online]. University of Washington, Seattle; 1993–2024
  25. Soons E, Bisseling TM, van Kouwen MCA, Möslein G, Siersema PD. Endoscopic management of duodenal adenomatosis in familial adenomatous polyposis—a case-based review. United Eur Gastroenterol J. 2021;9:461–8. [DOI: 10.1002/ueg2.12071]
  26. Dinarvand P, Davaro EP, Doan JV, Ising ME, Evans NR, Phillips NJ, et al. Familial adenomatous polyposis syndrome: an update and review of extraintestinal manifestations. Arch Pathol Lab Med. 2019;143:1382–98. [PMID: 31070935]
  27. Campos FG, Sulbaran M, Safatle-Ribeiro AV, Martinez CA. Duodenal adenoma surveillance in patients with familial adenomatous polyposis. World J Gastrointest Endosc. 2015;7:950–9. [PMID: 26265988]
  28. Beer A, Streubel B, Asari R, Dejaco C, Oberhuber G. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)—a rare recently described gastric polyposis syndrome—report of a case. Z Gastroenterol. 2017;55:1131–4. [PMID: 29141268]
  29. Li J, Woods SL, Healey S, Beesley J, Chen X, Lee JS, et al. Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am J Hum Genet. 2016;98:830–42. [PMID: 27087319]
  30. Garutti M, Foffano L, Mazzeo R, Michelotti A, Da Ros L, Viel A, et al. Hereditary cancer syndromes: a comprehensive review with a visual tool. Genes (Basel). 2023;14:1025. [PMID: 37239385]
  31. The National Comprehensive Cancer Network. NCCN Guidelines insights: genetic/familial high-risk assessment: colorectal, endometrial and gastric (Version 3.2024)
  32. Duarte M, Milikowski C. Gastrointestinal polyposis with associated cutaneous manifestations. Pathology. 2022;54:157–66. [PMID: 34763900]
  33. Boursi B, Sella T, Liberman E, Shapira S, David M, Kazanov D, et al. The APC p. I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews. Eur J Cancer. 2013;49:3680–5. [PMID: 23896379]
  34. Leshno A, Shapira S, Liberman E, Kraus S, Sror M, Harlap-Gat A, et al. The APC I1307K allele conveys a significant increased risk for cancer. Int J Cancer. 2016;138:1361–7. [PMID: 26421687]
  35. Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, et al. Inherited variants of MYH associated with somatic G:C–>T: a mutations in colorectal tumors. Nat Genet. 2002;30:227–32. [PMID: 11818965]
  36. Tahara YK, Kietrys AM, Hebenbrock M, Lee Y, Wilson DL, Kool ET. Dual inhibitors of 8-oxoguanine surveillance by OGG1 and NUDT1. ACS Chem Biol. 2019;14:2606–15. [PMID: 31622553]
  37. Nielsen M, Infante E, Brand R. MUTYH Polyposis. 2012 Oct 4 [updated 2021 May 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. University of Washington, Seattle; 1993–2024
  38. Aretz S, Tricarico R, Papi L, Spier I, Pin E, Horpaopan S, et al. MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events. Eur J Hum Genet. 2014;22:923–9. [PMID: 23361220]
  39. Theodoratou E, Campbell H, Tenesa A, Houlston R, Webb E, Lubbe S, et al. A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants. Br J Cancer. 2010;103:1875–84. [PMID: 21063410]
  40. Ali M, Kim H, Cleary S, Cupples C, Gallinger S, Bristow R. Characterization of mutant MUTYH proteins associated with familial colorectal cancer. Gastroenterology. 2008;135:499–507. [PMID: 18534194]
  41. Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, et al. Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet. 2003;362:39–41. [PMID: 12853198]
  42. Dolwani S, Williams GT, West KP, Newman J, Stock D, Griffiths AP, et al. Analysis of inherited MYH/(MutYH) mutations in British Asian patients with colorectal cancer. Gut. 2007;56:593. [PMID: 17369389]
  43. Kashfi SM, Golmohammadi M, Behboudi F, Nazemalhosseini-Mojarad E, Zali MR. MUTYH the base excision repair gene family member associated with colorectal cancer polyposis. Gastroenterol Hepatol Bed Bench. 2013;6(Suppl 1):S1-10. [PMID: 24834277]
  44. Nielsen M, Franken PF, Reinards TH, Weiss MM, Wagner A, van der Klift H, et al. Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). J Med Genet. 2005;42: e54. [PMID: 16140997]
  45. Nielsen M, Morreau H, Vasen HF, Hes FJ. MUTYH-associated polyposis (MAP). Crit Rev Oncol Hematol. 2011;79:1–16. [PMID: 20663686]
  46. García-Simón N, Valentín F, Royuela A, Hidalgo-Calero B, Blázquez-Martín R, de Miguel-Reyes M, et al. Optimizing genetic testing strategy for suspected attenuated adenomatous polyposis: effective solutions in public health systems. Clin Transl Oncol. 2024. https://doi.org/10.1007/s12094-024-03811-y . [DOI: 10.1007/s12094-024-03811-y]
  47. Thompson AB, Sutcliffe EG, Arvai K, Roberts ME, Susswein LR, Marshall ML, et al. Monoallelic MUTYH pathogenic variants ascertained via multi-gene hereditary cancer panels are not associated with colorectal, endometrial, or breast cancer. Fam Cancer. 2022;21:415–22. [PMID: 34981295]
  48. Colas C, Bonadona V, Baert-Desurmont S, Bonnet D, Coulet F, Dhooge M, et al. MUTYH-associated polyposis: review and update of the French recommendations established in 2012 under the auspices of the National Cancer institute (INCa). Eur J Med Genet. 2020;63: 104078. [PMID: 33059073]
  49. Win AK, Dowty JG, Cleary SP, Kim H, Buchanan DD, Young JP, et al. Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology. 2014;146:1208–11. [PMID: 24444654]
  50. Paller CJ, Tukachinsky H, Maertens A, Decker B, Sampson JR, Cheadle JP, et al. Pan-cancer interrogation of MUTYH variants reveals biallelic inactivation and defective base excision repair across a spectrum of solid tumors. JCO Precis Oncol. 2024;8: e2300251. [PMID: 38394468]
  51. Barreiro RAS, Sabbaga J, Rossi BM, Achatz MIW, Bettoni F, Camargo AA, et al. Monoallelic deleterious MUTYH germline variants as a driver for tumorigenesis. J Pathol. 2022;256:214–22. [PMID: 34816434]
  52. Giráldez MD, Balaguer F, Bujanda L, Cuatrecasas M, Muñoz J, Alonso-Espinaco V, et al. MSH6 and MUTYH deficiency is a frequent event in early-onset colorectal cancer. Clin Cancer Res. 2010;16:5402–13. [PMID: 20924129]
  53. Out AA, Wasielewski M, Huijts PE, van Minderhout IJ, Houwing-Duistermaat JJ, Tops CM, et al. MUTYH gene variants and breast cancer in a Dutch case–control study. Breast Cancer Res Treat. 2012;134:219–27. [PMID: 22297469]
  54. Win AK, Reece JC, Dowty JG, Buchanan DD, Clendenning M, Rosty C, et al. Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. Int J Cancer. 2016;139:1557–63. [PMID: 27194394]
  55. Gismondi V, Meta M, Bonelli L, Radice P, Sala P, Bertario L, et al. Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas. Int J Cancer. 2004;109:680–4. [PMID: 14999774]
  56. Beiner ME, Zhang WW, Zhang S, Gallinger S, Sun P, Narod SA. Mutations of the MYH gene do not substantially contribute to the risk of breast cancer. Breast Cancer Res Treat. 2009;114:575–8. [PMID: 18454351]
  57. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013;45:136–44. [PMID: 23263490]
  58. Miyabe I, Kunkel TA, Carr AM. The major roles of DNA polymerases epsilon and delta at the eukaryotic replication fork are evolutionarily conserved. PLoS Genet. 2011;7: e1002407. [PMID: 22144917]
  59. Palles C, Martin L, Domingo E, Chegwidden L, McGuire J, Cuthill V, et al. The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management. Fam Cancer. 2022;21:197–209. [PMID: 33948826]
  60. Mur P, García-Mulero S, Del Valle J, Magraner-Pardo L, Vidal A, Pineda M, et al. Role of POLE and POLD1 in familial cancer. Genet Med. 2020;22:2089–100. [PMID: 32792570]
  61. Ma X, Dong L, Liu X, Ou K, Yang L. POLE/POLD1 mutation and tumor immunotherapy. J Exp Clin Cancer Res. 2022;41:216. [PMID: 35780178]
  62. Magrin L, Fanale D, Brando C, Fiorino A, Corsini LR, Sciacchitano R, et al. POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes. Oncogene. 2021;40:5893–901. [PMID: 34363023]
  63. Schubert SA, Morreau H, de Miranda NFCC, van Wezel T. The missing heritability of familial colorectal cancer. Mutagenesis. 2020;35:221–31. [PMID: 31605533]
  64. Andrianova MA, Seplyarskiy VB, Terradas M, Sánchez-Heras AB, Mur P, Soto JL, et al. Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells. Eur J Hum Genet. 2024;32:837–45. [PMID: 38658779]
  65. Weren RD, Ligtenberg MJ, Kets CM, de Voer RM, Verwiel ET, Spruijt L, et al. A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Nat Genet. 2015;47:668–71. [PMID: 25938944]
  66. Fostira F, Kontopodis E, Apostolou P, Fragkaki M, Androulakis N, Yannoukakos D, et al. Extending the clinical phenotype associated with biallelic NTHL1 germline mutations. Clin Genet. 2018;94:588–9. [PMID: 30248171]
  67. Kuiper RP, Nielsen M, De Voer RM, Hoogerbrugge N. NTHL1 tumor syndrome. 2020 Apr 2. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. University of Washington, Seattle; 1993–2024
  68. Chan JM, Clendenning M, Joseland S, Georgeson P, Mahmood K, Walker R, et al. Rare germline variants in the AXIN2 gene in families with colonic polyposis and colorectal cancer. Fam Cancer. 2022;21:399–413. [PMID: 34817745]
  69. Orphanet Rare Diseases. AXIN2-related attenuated familial adenomatous polyposis. [Online]. https://www.orpha.net/en/disease/detail/401911 . Accessed 14 June 2024
  70. Beard C, Purvis R, Winship IM, Macrae FA, Buchanan DD. Phenotypic confirmation of oligodontia, colorectal polyposis and cancer in a family carrying an exon 7 nonsense variant in the AXIN2 gene. Fam Cancer. 2019;18:311–5. [PMID: 30671715]
  71. Adam R, Spier I, Zhao B, Kloth M, Marquez J, Hinrichsen I, et al. Exome sequencing identifies biallelic MSH3 germline mutations as a recessive subtype of colorectal adenomatous polyposis. Am J Hum Genet. 2016;99:337–51. [PMID: 27476653]
  72. Terradas M, Munoz-Torres PM, Belhadj S, Aiza G, Navarro M, Brunet J, et al. Contribution to colonic polyposis of recently proposed predisposing genes and assessment of the prevalence of NTHL1- and MSH3-associated polyposes. Hum Mutat. 2019;40:1910–23. [PMID: 31243857]
  73. Aelvoet AS, Hoekman DR, Redeker BJW, Weegenaar J, Dekker E, van Noesel CJM, et al. A large family with MSH3-related polyposis. Fam Cancer. 2023;22:49–54. [PMID: 35675019]
  74. Villy MC, Masliah-Planchon J, Schnitzler A, Delhomelle H, Buecher B, Filser M, et al. MSH3: a confirmed predisposing gene for adenomatous polyposis. J Med Genet. 2023;60:1198–205. [PMID: 37402566]
  75. Olkinuora A, Nieminen TT, Mårtensson E, Rohlin A, Ristimäki A, Koskenvuo L, et al. Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition. Genet Med. 2019;21:1868–73. [PMID: 30573798]
  76. Lipkin SM, Wang V, Stoler DL, Anderson GR, Kirsch I, Hadley D, et al. Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: evidence for somatic mutation in colorectal cancers. Hum Mutat. 2001;17:389–96. [PMID: 11317354]
  77. Nawaz S, Ullah MI, Hamid BS, Nargis J, Nawaz M, Hussain S, et al. A loss-of-function variant in DNA mismatch repair gene MLH3 underlies severe oligozoospermia. J Hum Genet. 2021;66:725–30. [PMID: 33517345]
  78. Chen S, Wang G, Zheng X, Ge S, Dai Y, Ping P, et al. Whole-exome sequencing of a large Chinese azoospermia and severe oligospermia cohort identifies novel infertility causative variants and genes. Hum Mol Genet. 2020;29:2451–9. [PMID: 32469048]
  79. Colas C, Brugières L, Wimmer K. constitutional mismatch repair deficiency. In: Valle L, Gruber S, Capellá G, editors. Hereditary colorectal cancer. Cham: Springer; 2018.
  80. Aronson M, Gallinger S, Cohen Z, Cohen S, Dvir R, Elhasid R, et al. Gastrointestinal findings in the largest series of patients with hereditary biallelic mismatch repair deficiency syndrome: report from the international consortium. Am J Gastroenterol. 2016;111:275–84. [PMID: 26729549]
  81. Bellacosa A. Role of MED1 (MBD4) gene in DNA repair and human cancer. J Cell Physiol. 2001;187:137–44. [PMID: 11267993]
  82. Palles C, West HD, Chew E, Galavotti S, Flensburg C, Grolleman JE, et al. Germline MBD4 deficiency causes a multi-tumor predisposition syndrome. Am J Hum Genet. 2022;109:953–60. [PMID: 35460607]
  83. Griffin BL, Majhail NS, Lesmana H. Germline biallelic loss in MBD4 leading to early onset AML with hyper-mutator genomic signature. Blood. 2021;138:3385. [DOI: 10.1182/blood-2021-154221]
  84. Palles C, Chew E, Grolleman JE, Gavalotti, S, Flensburg C, Jansen EAM, et al. Germline loss-of-function variants in the base-excision repair gene MBD4 cause a Mendelian recessive syndrome of adenomatous colorectal polyposis and acute myeloid leukaemia. bioRxiv [Preprint]. April 28, 2021 [cited 2024 July 1]. Available from: https://doi.org/10.1101/2021.04.27.441137140
  85. Terradas M, Gonzalez-Abuin N, García-Mulero S, Viana-Errasti J, Aiza G, Piulats JM, et al. MBD4-associated neoplasia syndrome: screening of cases with suggestive phenotypes. Eur J Hum Genet. 2023;31:1185–9. [PMID: 37402954]
  86. Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, et al. Diagnosis and management of cancer risk in the gastrointestinal hamartomatous polyposis syndromes: recommendations from the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2022;117:846–64. [PMID: 35471415]
  87. Wagner A, Aretz S, Auranen A, Bruno MJ, Cavestro GM, Crosbie EJ, et al. The management of Peutz-Jeghers syndrome: European Hereditary Tumour Group (EHTG) Guideline. J Clin Med. 2021;10:473. [PMID: 33513864]
  88. Orphanet Rare Diseases. Juvenile polyposis syndrome. [Online]. https://www.orpha.net/en/disease/detail/2929 . Accessed 14 June 2024
  89. Liu S, Ma Y, You W, Li J, Li JN, Qian JM. Hamartomatous polyposis syndrome associated malignancies: risk, pathogenesis and endoscopic surveillance. J Dig Dis. 2021;2:444–51. [DOI: 10.1111/1751-2980.13029]
  90. Orphanet Rare Diseases. Peutz-Jeghers syndrome. [Online]. https://www.orpha.net/en/disease/detail/2869 . Accessed 14 June 2024
  91. Valentín F, de Tejada AH, Gonzaléz-Vioque E, García-Simón N, Sánchez A, Romero A. The c.386A>C p.(Asn129Thr) variant in SMAD4 is likely to be pathogenic, causing juvenile polyposis syndrome. A case report of a mosaic variant. Mol Genet Genomic Med. 2024;12:e2348. [PMID: 38146137]
  92. Matsumoto T, Umeno J, Jimbo K, Arai M, Iwama I, Kashida H, et al. Clinical guidelines for diagnosis and management of juvenile polyposis syndrome in children and adults-secondary publication. J Anus Rectum Colon. 2023;7:115–25. [PMID: 37113581]
  93. McDonald J, Stevenson DA. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [Updated 2021 Nov 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A editors. GeneReviews® [Online]. University of Washington, Seattle; 1993–2024. https://www.ncbi.nlm.nih.gov/books/NBK1351/ . Accessed 14 June 2024
  94. Larsen Haidle J, MacFarland SP, Howe JR. Juvenile Polyposis Syndrome. 2003 May 13 [updated 2022 Feb 3]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Online]. University of Washington, Seattle; 1993–2024. PMID: 20301642. Accessed 14 June 2024
  95. Hendricks LAJ, Hoogerbrugge N, Schuurs-Hoeijmakers JHM, Vos JR. A review on age-related cancer risks in PTEN hamartoma tumor syndrome. Clin Genet. 2021;99:219–25. [PMID: 33140411]
  96. Tischkowitz M, Colas C, Pouwels S, Hoogerbrugge N, PHTS Guideline Development Group, European Reference Network GENTURIS. Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome. Eur J Hum Genet. 2020;28:1387–93. [PMID: 32533092]
  97. Nelen MR, Kremer H, Konings IB, Schoute F, van Essen AJ, Koch R, et al. Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet. 1999;7:267–73. [PMID: 10234502]
  98. Carballal S, Balaguer F, IJspeert JEG. Serrated polyposis syndrome; epidemiology and management. Best Pract Res Clin Gastroenterol. 2022;58–59:101791. [PMID: 35988960]
  99. Gala MK, Mizukami Y, Le LP, Moriichi K, Austin T, Yamamoto M, et al. Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas. Gastroenterology. 2014;146:520–9. [PMID: 24512911]
  100. Whitelaw SC, Murday VA, Tomlinson IP, Thomas HJ, Cottrell S, Ginsberg A, et al. Clinical and molecular features of the hereditary mixed polyposis syndrome. Gastroenterology. 1997;112:327–34. [PMID: 9024286]
  101. Jaeger E, Leedham S, Lewis A, Segditsas S, Becker M, Cuadrado PR, et al. Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat Genet. 2012;44:699–703. [PMID: 22561515]
  102. Rohlin A, Eiengård F, Lundstam U, Zagoras T, Nilsson S, Edsjö A, et al. GREM1 and POLE variants in hereditary colorectal cancer syndromes. Genes Chromosomes Cancer. 2016;55:95–106. [PMID: 26493165]

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