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The Hereditary Syndromes

  • Chapter
Multiple Primary Malignancies

Part of the book series: Updates in Surgery ((UPDATESSURG))

Abstract

Within the ambit of multiple tumors, an important issue is that of already identified hereditary syndromes, a group of anatomical-clinical entities that have been well distinguished and studied for years. Such diseases have a common etiopathogenetic mechanism, mostly represented by a genetic mutation. It is easy to understand how a patient, who has in his or her genetic history a genomic alteration, could develop multiple tumors.

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References

  1. Renda A, Izzo P, D’Armeinto F et al (2004) Chirurgia oncologica “Dna-guidata”. Archivio e Atti SIC, Pozzi, Rome, 1:141–172

    Google Scholar 

  2. Rolandelli RH, Roslin JJ (2003) Colon. In: Sabiston DC (ed) Trattato di chirurgia. Le basi biologiche della moderna pratica chirurgica, prima edizione italiana sulla sedicesima americana. Delfino Editore, Rome, pp 662–696

    Google Scholar 

  3. Bertario L, Russo A, Sala P et al (2003) Multiple approach to the exploration of genotypephenotype correlations in familial adenomatous polyposis. J Clin Oncol 21(9): 1698–1707

    Article  PubMed  CAS  Google Scholar 

  4. Soravia C, Berk T, Madlensky L et al (1998) Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet 62(6): 1290–1301

    Article  PubMed  CAS  Google Scholar 

  5. Lal G, Gallinger S (2000) Familial adenomatous polyposis. Semin Surg Oncol 18(4):314–323

    Article  PubMed  CAS  Google Scholar 

  6. Lynch HT, Smyrk TC, McGinn T et al (1995) Attenuated familial adenomatous polyposis (AFAP): a phenotipically and genotipically distinctive variant of FAP. Cancer 76:2427–2433

    Article  PubMed  CAS  Google Scholar 

  7. Arvanitis ML, Jagelman DG, Fazio VW et al (1990) Mortality in patients with familial adenomatous polyposis. Dis Col & Rectum 33(8):639–642

    Article  CAS  Google Scholar 

  8. Giardiello FM, Brensinger JD, Tersmette AC et al (2000) Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119:1447–1453

    Article  PubMed  CAS  Google Scholar 

  9. Lynch HT, Krush AJ (1971) Cancer family G revisited: 1895-1970. Cancer 27:1505–1511

    Article  PubMed  CAS  Google Scholar 

  10. Warthin AS (1913) Heredity with reference to carcinoma. Arch Intern Med 12:546–555

    Google Scholar 

  11. Warthin AS (1925) The further study of a cancer family. J Cancer Res 9:279–286

    Google Scholar 

  12. Rijcken FE, Mourits MJ, Kleibeuker JH et al (2003) Gynecologic screening in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 91(1):74–80

    Article  PubMed  Google Scholar 

  13. Moslein G (2003) Clinical implications of molecular diagnosis in hereditary nonpolyposis colorectal cancer. Recent Results Cancer Res 162:73–78

    PubMed  Google Scholar 

  14. Moley JF, Wells SA Jr (2003) Ipofisi e surreni. In: Sabiston DC (ed) Trattato di chirurgia. Le basi biologiche della moderna pratica chirurgica, prima edizione italiana sulla sedicesima americana. Delfino Editore, Rome, pp 662–696

    Google Scholar 

  15. Lévy-Bohbot N, Merle C, Goudet P et al (2004) Prevalence, characteristics and prognosisof MEN 1-associated glucagonomas, VIPomas,and somatostatinomas Study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol 28:1075–1081

    Article  PubMed  Google Scholar 

  16. Calender A, Cadiot G, Mignon M (2001) Néoplasie endocrinienne multiple de type 1: aspects génétiques et cliniques. Gastroenterol Clin Biol 25:B38–B48

    PubMed  CAS  Google Scholar 

  17. Chanson P, Cadiot G, Murat A (1997) Management of patients and subjects at risk for multiple endocrine neoplasia type 1: MEN 1. GENEM 1. Groupe d’Etude des Neoplasies Endocriniennes Multiples de type 1. Horm Res 47:211–220

    Article  PubMed  CAS  Google Scholar 

  18. Marx S, Spiegel AM, Skarulis MC et al (1998) Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med 129:484–494

    PubMed  CAS  Google Scholar 

  19. Cadiot G, Mignon M, Gresze (2003) Diagnostique des tumeurs endocrines de la région duodéno-pancréatique. Gastroenterol Clin Biol 27:S6–S14

    PubMed  Google Scholar 

  20. Skogseid B, Oberg K, Benson L et al (1987) A standardized meal stimulation test of the endocrine pancreas for early detection of pancreatic endocrine tumors in multiple endocrine neoplasia type 1 syndrome: five years experience. J Clin Endocrinol Metab 64:1233–1240

    Article  PubMed  CAS  Google Scholar 

  21. Triponez F, Dosseh D, Goudet P et al (2006) Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 243:265–272

    Article  PubMed  Google Scholar 

  22. Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671

    Article  PubMed  CAS  Google Scholar 

  23. Doherty GM, Thompson NW (2003) Multiple endocrine neoplasia type 1: duodenopancreatic tumours. J Intern Med 253:590–598

    Article  PubMed  CAS  Google Scholar 

  24. Wilkinson S, Teh BT, Davey KR et al (1993) Cause of death in multiple endocrine neoplasia type 1. Arch Surg 128:683–690

    PubMed  CAS  Google Scholar 

  25. Dean PG, van Heerden JA, Farley DR et al (2000) Are patients with multiple endocrine neoplasia type I prone to premature death? World J Surg 24:1437–1441

    Article  PubMed  CAS  Google Scholar 

  26. Ebeling T, Vierimaa O, Kyto S et al (2004) Effect of multiple endocrine neoplasia type 1 (MEN1) gene mutations on premature mortality in familial MEN1 syndrome with founder mutations. J Clin Endocrinol Metab 89(7):3392–3396

    Article  PubMed  CAS  Google Scholar 

  27. Geerdink EAM, Van der Luijtl RB, Lips CJ (2003) Do patients with multiple endocrine neoplasia benefit from periodical screening? Eur J Endocrinol 149:577–582

    Article  PubMed  CAS  Google Scholar 

  28. Marini F, Falchetti A, Del Monte F et al (2006) Multiple endocrine neoplasia type 2. Orphanet J Rare Dis 1:45

    Article  PubMed  Google Scholar 

  29. Farnebo F, Kytola S, Teh BT et al (1999) Alternative genetic pathways in parathyroid tumorigenesis. J Clin Endocrinol Metab 84:3775–3780

    Article  PubMed  CAS  Google Scholar 

  30. Lips CJ, Landsvater RM, Hoppener JW et al (1994) Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331:828–835

    Article  PubMed  CAS  Google Scholar 

  31. Robinson MF, Furst EJ, Nunziata V et al (1992) Characterization of the clinical features of five families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2. Henry Ford Hosp Med J 40:249–252

    PubMed  CAS  Google Scholar 

  32. Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671

    Article  PubMed  CAS  Google Scholar 

  33. Papotti M, Botto Micca F et al (1993) Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular, trabecular, and solid patterns. Am J Surg Pathol 17:291–301

    Article  PubMed  CAS  Google Scholar 

  34. Carling T (2005) Multiple endocrine neoplasia syndrome: genetic basis for clinical management. Curr Opin Oncol 17:7–12

    Article  PubMed  Google Scholar 

  35. Eng C (1996) The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung’s disease. N Engl J Med 335:943–951

    Article  PubMed  CAS  Google Scholar 

  36. Dralle H, Gimm O, Simon D et al (1998) Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experience. World J Surg 22:744–750

    Article  PubMed  CAS  Google Scholar 

  37. Neumann HP, Bausch B, McWhinney SR et al (2002) Freiburg-Warsaw-Columbus Pheochromocytoma Study Group. “Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346:1459–1466

    Article  PubMed  CAS  Google Scholar 

  38. Yarden RI, Papa MZ (2006) BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions. Mol Cancer Ther 5(6): 1396–1404

    Article  PubMed  CAS  Google Scholar 

  39. Schmeler KM, Sun CC, Bodurka DC et al (2006) Prophylactic bilateral salpingo-oophorectomy compared with surveillance in women with BRCA mutations. Obstet Gynecol 108:515–520

    PubMed  Google Scholar 

  40. Ford D, Easton DF, Stratton M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676–689

    Article  PubMed  CAS  Google Scholar 

  41. Struewing JP, Hartge P, Wacholder S et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401–1408

    Article  PubMed  CAS  Google Scholar 

  42. Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130

    Article  PubMed  CAS  Google Scholar 

  43. Eisinger F (1998) Recommendations for medical management of hereditary breast and ovarian cancer: The French National Ad Hoc Committee. Ann Oncol 9:939–950

    Article  PubMed  CAS  Google Scholar 

  44. Robson ME (2002) Clinical considerations in the management of individuals at risk for hereditary breast and ovarian cancer. Cancer Control 6:457–465

    Google Scholar 

  45. Peterson G (1999) Genetic testing for cancer: the surgeon’s critical role. Clinical cancer genetics: 1998 (what’s available to you in your practice). J Am Coll Surg 188(1):89–93

    PubMed  CAS  Google Scholar 

  46. Hernegger GS, Moore HG, Guillem JG (2002) Attenuated familial adenomatous polyposis: an evolving and poorly understood entity. Dis Colon Rectum 45:127–136

    Article  PubMed  Google Scholar 

  47. Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 348:709–715

    Article  Google Scholar 

  48. Ames BN, Gold LS (1991) Endogenous mutagens and the causes of aging and cancer. Mutat Res 250:3–16

    PubMed  CAS  Google Scholar 

  49. Al-Tassan N, Chmiel NH, Maynard J et al (2002) Inherited variants of MYH associated with somatic G:C fi T:A mutations in colorectal tumors. Nat Genet 30:227–232

    Article  PubMed  CAS  Google Scholar 

  50. Enholm S, Hienonen T, Suomalainen A et al (2003) Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finish colorectal cancer patients. Am J Pathol 163:827–832

    PubMed  CAS  Google Scholar 

  51. Halford SE, Rowan AJ, Lipton L et al (2003) Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers. Am J Pathol 162:1545–1548

    PubMed  CAS  Google Scholar 

  52. Jones S, Emmerson P, Maynard J et al (2002) Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C fi T:A mutations. Hum Mol Genet 11:2961–2967

    Article  PubMed  CAS  Google Scholar 

  53. Sampson JR, Dolwani S, Jones S et al (2003) Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet 362:39–41

    Article  PubMed  CAS  Google Scholar 

  54. Sieber OM, Lipton L, Crabtree M et al (2003) Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348:791–799

    Article  PubMed  Google Scholar 

  55. Venesio T, Molatore S, Cattaneo F et al (2004) High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Gastroenterology 126:1681–1685

    Article  PubMed  CAS  Google Scholar 

  56. Jones S, Lambert S, Williams GT et al (2004) Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas. Br J Cancer 90:1591–1593

    Article  PubMed  CAS  Google Scholar 

  57. Leite JS, Isidro G, Martins M et al (2005) Is prophylactic colectomy indicated in patients with MYH-associated polyposis? Colorectal Dis 7:327–331

    Article  PubMed  CAS  Google Scholar 

  58. Chandrasekharappa SC, Guru SC, Manickam P et al (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276:404–407

    Article  PubMed  CAS  Google Scholar 

  59. Lemmens I, Van de Ven WJ, Kas K et al (1997) Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN 1. Hum Mol Genet 6:1177–1183

    CAS  Google Scholar 

  60. Schnepp RW, Chen YX, Wang H et al (2006) Mutation of tumor suppressor gene Men1 acutely enhances proliferation of pancreatic islet cells. Cancer Res 66(11):5707–5715

    Article  PubMed  CAS  Google Scholar 

  61. Agarwal SK, Novotny EA, Crabtree JS et al (2003) Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter. Proc Natl Acad Sci USA 100:10770–10775

    Article  PubMed  CAS  Google Scholar 

  62. Kaji H, Canaff L, Lebrun JJ et al (2001) Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type h signalling. Proc Natl Acad Sci USA 98:3837–3842

    Article  PubMed  CAS  Google Scholar 

  63. Schnepp RW, Hou Z, Wang H et al (2004) Functional interaction between tumor suppressor menin and activator of S-phase kinase. Cancer Res 64:6791–6796

    Article  PubMed  CAS  Google Scholar 

  64. Kumagai H, Sato N, Yamada M et al (1999) A novel growth-and cell cycle-regulatedprotein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells. Mol Cell Biol 19:5083–5095

    PubMed  CAS  Google Scholar 

  65. Masai H, Matsui E, You Z et al (2000) Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a critical threonine residue of Cdc7 bY Cdks. J Biol Chem 275:42–52

    Article  Google Scholar 

  66. Howe JR, Moley JF, Goodfellow P, Wells SA Jr (1993) Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet 2:851–856

    Article  PubMed  Google Scholar 

  67. Mulligan LM, Kwok JB, Healey CS et al (1993) Germ-line mutations of the RET protooncogene in multiple endocrine neoplasia type 2A. Nature 363:458–460

    Article  PubMed  CAS  Google Scholar 

  68. Da Silva AM, Maciel RM, Da Silva MR et al (2003) A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma. J Clin Endocrinol Metab 88:5438–5443

    Article  PubMed  CAS  Google Scholar 

  69. Jing S, Wen D, Yu Y et al (1996) GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 85:1113–1124

    Article  PubMed  CAS  Google Scholar 

  70. Santoro M, Melillo RM, Carlomagno F et al (2004) RET: normal and abnormal functions. Endocrinology 145:5448–5451

    Article  PubMed  CAS  Google Scholar 

  71. Santoro M, Carlomagno F, Melillo RM, Fusco A (2004) Dysfunction of the RET receptor in human cancer. Cell Mol Life Sci 61:2954–2964

    Article  PubMed  CAS  Google Scholar 

  72. Jain S, Watson MA, DeBenedetti MK et al (2004) Expression profiles provide insights into early malignant potential and skeletal abnormalities in multiple endocrine neoplasia type 2B syndrome tumors. Cancer Res 64:3907–3913

    Article  PubMed  CAS  Google Scholar 

  73. Thull DL, Vogel VG (2004) Recognition and management of hereditary breast cancer syndromes. Oncologist 9:13–24

    Article  PubMed  Google Scholar 

  74. Carlomagno N, Scarano MI, Gargiulo S et al (2001) Familial colonic polyposis: effect of molecular analysis on the diagnostic-therapeutic approach. Ann Ital Chir 72(2):207–214

    PubMed  CAS  Google Scholar 

  75. Traboulsi EI, Apostolides J, Giardiello FM et al (1996) Pigmented ocular fundus lesions and APC mutations in familial adenomatous polyposis. Ophthalmic Genet 17(4): 167–174

    Article  PubMed  CAS  Google Scholar 

  76. Olschwang S, Laurent-Puig P, Thuille B et al (1992) Frequent polymorphism in the 13th exon of the adenomatous polyposis coli gene. Hum Genet 90:161–163

    Article  PubMed  CAS  Google Scholar 

  77. Nagase H, Miyoshi Y, Horii A et al (1992) Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Res 52:4055–4057

    PubMed  CAS  Google Scholar 

  78. Wu JS, Mc Gannon EA, Church JM (1998) APC genotype, polyp number and surgical options in familial adenomatous polyposis. Ann Surg 227:57–62

    Article  PubMed  CAS  Google Scholar 

  79. Nordling M, Engwall Y, Wahistrom J et al (1997) Novel mutations in APC gene and clinical features in Swedish patients with polyposis coli. Am Cancer Res 17:4275–4280

    CAS  Google Scholar 

  80. Caspari R, Friedi W, Mandl M et al (1994) Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer. Lancet 343:629–632

    Article  PubMed  CAS  Google Scholar 

  81. Presciuttini S, Varesco L, Sala P et al (1994) Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations. Ann Hum Genet 58:331–342

    Article  PubMed  CAS  Google Scholar 

  82. Giardiello FM, Krush AJ, Petersen GM et al (1994) Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation. Gastroenterology 106(6): 1542–1547

    PubMed  CAS  Google Scholar 

  83. Giardiello FM, Brensinger JD, Luce MC et al (1997) Phenotypic expression of disease in families that have mutations in the 5’ region of the adenomatous polyposis coli gene. Ann Intern Med 126(7):514–519

    PubMed  CAS  Google Scholar 

  84. Cunningham C, Dunlop MG (1996) Molecular genetic basis of colo-rectal cancer susceptibility. Br J Surg 83:321–329

    Article  PubMed  CAS  Google Scholar 

  85. Leggett BA, Young IP, Biden K et al (1997) Severe upper gastrointestinal polyposis associated with sparse colonie polyposis in a familial adenomatous polyposis family with an APC mutation at codon 1250. Gut 41:518–521

    Article  PubMed  CAS  Google Scholar 

  86. Nugent KP, Phillips RK, Hodgson SV et al (1994) Phenotypic expression in familial adenomatous polyposis: partial prediction by mutation analysis. Gut 35:1622–1623

    Article  PubMed  CAS  Google Scholar 

  87. Spirio L, Otterud B, Stauffer D et al (1992) Linkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus. Am J Hum Genet 51(1):92–100

    PubMed  CAS  Google Scholar 

  88. Olschwang S, Tiret A, Laurent-Puig P et al (1993) Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients. Cell 75(5):959–968

    Article  PubMed  CAS  Google Scholar 

  89. Caspari R, Olschwang S, Friedl W et al (1995) Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 4(3):337–340

    Article  PubMed  CAS  Google Scholar 

  90. Davies DR, Armstrong JG, Thakker N et al (1995) Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene. Am J Hum Genet 57(5):1151–1158

    PubMed  CAS  Google Scholar 

  91. Moisio A-L, Jarvinen H, Peltomaki P (2002) Genetic and clinical characterisation of familial adenomatous polyposis: a population-based study. Gut 50:845–850

    Article  PubMed  CAS  Google Scholar 

  92. Gebert JF, Dupon C, Kadmon M et al (1999) Combined molecular and clinical approaches for the identification of families with familial adenomatous polyposis coli. Ann Surg 229:350–361

    Article  PubMed  CAS  Google Scholar 

  93. Friedl W, Caspari R, Sengteller M et al (2001) Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. Gut 48:515–521

    Article  PubMed  CAS  Google Scholar 

  94. Matsumoto T, Lida M, Kobori Y et al (2002) Genetic predisposition to clinical manifestations in familial adenomatous polyposis with special reference to duodenal lesions. Am J Gastroenterol 97:180–185

    Article  PubMed  Google Scholar 

  95. Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96(4):261–268

    Article  PubMed  CAS  Google Scholar 

  96. Eccles DM (2004) Hereditary cancer: guidelines in clinical practice. Breast and ovarian cancer genetics Ann Oncol 15(Suppl 4): iv133–iv138

    Google Scholar 

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Carlomagno, N. et al. (2009). The Hereditary Syndromes. In: Multiple Primary Malignancies. Updates in Surgery. Springer, Milano. https://doi.org/10.1007/978-88-470-1095-6_8

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