Download PDF
Clin Colon Rectal Surg 2002; 15(2): 105-112
DOI: 10.1055/s-2002-32058
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Familial Adenomatous Polyposis

Joel E. Goldberg, W. Brian Perry
  • Department of General Surgery, 859th MSGS/MCSG, Wilford Hall Medical Center, United States Air Force, Lackland AFB, TX
Further Information

Publication History

Publication Date:
06 June 2002 (online)

Also available at
    Permissions and Reprints

ABSTRACT

With 160,000 new cases diagnosed each year, colorectal carcinoma is the third most common malignancy in the United States. Twenty percent of all cases are secondary to an inherited genetic trait. Familial adenomatous polyposis (FAP) accounts for 1% of all colorectal cancers. Germline mutations in the adenomatous polyposis coli gene, mapped to chromosome 5q21, have been linked to this inherited form of colorectal cancer. Over 400 different mutations have been identified. Phenotypic expression of the disease is variable, ranging from an early-onset aggressive form to a late-onset attenuated variant. FAP has three notable forms. Gardner's syndrome is FAP associated with multiple soft tissue and bony abnormalities, ocular lesions, and upper gastrointestinal (GI) polyposis. Turcot's syndrome is adenomatous polyposis associated with central nervous system tumors. Attenuated FAP is a late onset disease (after 50 years of age). Patients with attenuated FAP have fewer polyps (fewer than 100) that are more proximal in location. Individuals diagnosed with FAP have a 100% lifetime risk of developing colorectal cancer. Moreover, they are at risk for duodenal and periampullary adenocarcinoma as well as desmoid tumors. Successful treatment of these patients depends upon early diagnosis. Therapeutic options include prophylactic colectomy with ileorectal anastomosis, total proctocolectomy with ileal pouch anal anastomosis reconstruction, or end ileostomy. Surveillance of the upper GI tract is necessary to evaluate for duodenal adenomatosis. Progressive adenomatosis, severe dysplasia in a polyp, or duodenal/periampullary adenocarcinoma are indications for surgical intervention. The development of polyposis registries, genetic testing, genetic counseling, and early screening colonoscopy are essential to early diagnosis and successful management of this disease.

KEYWORDS

Familial adenomatous polyposis - adenomatous polyposis coli - inherited colorectal cancer - Gardner's syndrome - Turcot's syndrome - attenuated familial adenomatous polyposis

REFERENCES

  • 1 Greenlee R T, Murray T, Bolden S, Wingo P A. Cancer statistics, 2000.  Cancer J Clin . 2000;  50 7-33
    CrossrefPubMedSearch in Google Scholar
  • 2 Rustgi A K. Hereditary gastrointestinal polyposis and nonpolyposis syndromes.  N Engl J Med . 1994;  331 1694-1702
    CrossrefPubMedSearch in Google Scholar
  • 3 Winawer S J, Schottenfeld D, Flehinger B J. Colorectal cancer screening.  J Natl Cancer Inst . 1991;  83 243-253
    PubMedSearch in Google Scholar
  • 4 Burt R W. Colon cancer screening.  Gastroenterology . 2000;  119 837-853
    CrossrefPubMedSearch in Google Scholar
  • 5 Kinzler K W, Vogelstein B. Lessons from hereditary colorectal cancer.  Cell . 1996;  87 159-170
    CrossrefPubMedSearch in Google Scholar
  • 6 Wilmink A. Overview of the epidemiology of colorectal cancer.  Dis Colon Rectum . 1997;  40 483-493
    CrossrefPubMedSearch in Google Scholar
  • 7 Fearon E R, Vogelstein B. A genetic model for colorectal tumorigenesis.  Cell . 1990;  61 759-767
    CrossrefPubMedSearch in Google Scholar
  • 8 Vogelstein B, Fearon E R, Hamilton S R. Genetic alterations during colorectal tumor development.  N Engl J Med . 1988;  319 525-532
    CrossrefPubMedSearch in Google Scholar
  • 9 Guillem J G, Smith A J, Culle J, Ruo L. Gastrointestinal polyposis syndromes.  Curr Prob Surg . 1999;  36 219-323
    PubMedSearch in Google Scholar
  • 10 Soravia C, Berk T, Cohen Z. Genetic testing and surgical decision making in hereditary colorectal cancer.  In J Colorectal Dis . 2000;  15 21-28
    CrossrefPubMedSearch in Google Scholar
  • 11 Giardiello F M, Offerhaus J GA. Phenotype and cancer risk of various polyposis syndromes.  Eur J Cancer . 1995;  31A 1085-1087
    PubMedSearch in Google Scholar
  • 12 Bisgaard M L, Fenger K, Bulow S. Familial adenomatous polyposis (FAP): frequency, penetrance and mutation rate.  Hum Mutat . 1994;  3 121-125
    CrossrefPubMedSearch in Google Scholar
  • 13 Distante S, Nasioulas S, Somers G R. Familial adenomatous polyposis in a 5 year old child: a clinical, pathological, and a molecular genetic study.  J Med Genet . 1996;  33 157-160
    CrossrefPubMedSearch in Google Scholar
  • 14 Haggitt R C, Reid B J. Hereditary gastrointestinal polyposis syndromes.  Am J Surg Pathol . 1986;  10 871-887
    PubMedSearch in Google Scholar
  • 15 Rustin R B, Jagelman D G, McGannon E. Spontaneous mutation in familial adenomatous polyposis.  Dis Colon Rectum . 1990;  33 52-55
    CrossrefPubMedSearch in Google Scholar
  • 16 Herrera L, Kakati S, Gibas L. Brief clinical report: Gardner syndrome in a man with an interstitial deletion of 5q.  Am J Med Genet . 1986;  25 473-476
    CrossrefPubMedSearch in Google Scholar
  • 17 Groden J, Thliveris A, Samowitz W. Identification and characterization of the familial adenomatous polyposis coli gene.  Cell . 1991;  66 589-600
    CrossrefPubMedSearch in Google Scholar
  • 18 Kinzler K W, Nilbert M C, Su L K. Identification of FAP locus genes from chromosome 5q21.  Science . 1991;  253 661-664
    CrossrefPubMedSearch in Google Scholar
  • 19 Leppert M, Dobbs M, Scambler P. The gene for familial polyposis coli maps to the long arm of chromosome 5.  Science . 1987;  238 1411-1413
    PubMedSearch in Google Scholar
  • 20 O'Sullivan M J, McCarthy T V, Doyle C T. Familial adenomatous polyposis, from bedside to benchside.  Am J Clin Pathol . 1998;  109 521-526
    PubMedSearch in Google Scholar
  • 21 King J E, Dozois R R, Lindor N M. Care of patients and their families with familial adenomatous polyposis.  Mayo Clin Proc . 2000;  5 57-67
    PubMedSearch in Google Scholar
  • 22 Chung D C. The genetic basis of colorectal cancer: insights into critical pathways of tumorigenesis.  Gastroenterology . 2000;  119 854-865
    CrossrefPubMedSearch in Google Scholar
  • 23 Corredor J, Wambach J, Barnard J. Gastrointestinal polyps in children: advances in molecular genetics, diagnosis, and management.  J Pediatr . 2001;  138 621-628
    CrossrefPubMedSearch in Google Scholar
  • 24 Rozen P, Samuel Z, Shomrat R, Legum C. Notable intrafamilial phenotypic variability in a kindred with familial adenomatous polyposis and an APC mutation in exon 9.  Gut . 1999;  45 829-833
    PubMedSearch in Google Scholar
  • 25 Giardiello F M, Krush A J, Petersen G M. Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation.  Gastroenterology . 1994;  106 1542-1547
    CrossrefPubMedSearch in Google Scholar
  • 26 Olschwang S, Tiret A, Laurent-Puig P. Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients.  Cell . 1993;  75 959-968
    CrossrefPubMedSearch in Google Scholar
  • 27 Caspari R, Olschwang S, Friedl W. Familial adenomatous polyposis: desmoid tumors and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444.  Hum Mol Genet . 1995;  4 337-340
    PubMedSearch in Google Scholar
  • 28 Clark S K, Phillips R KS. Desmoids in familial adenomatous polyposis.  Br J Surg . 1996;  83 1494-1504
    CrossrefPubMedSearch in Google Scholar
  • 29 Giardiello F M, Brensuinger J D, Luce M C. Phenotypic expression of disease in families that have mutations in the 5′ region of the adenomatous polyposis coli gene.  Ann Intern Med . 1997;  126 514-519
    PubMedSearch in Google Scholar
  • 30 Soravia C, Berk T, Madlensky L. Genotype-phenotype correlations in attenuated adenomatous polyposis coli.  Am J Hum Genet . 1998;  62 1290-1301
    CrossrefPubMedSearch in Google Scholar
  • 31 Gayther S A, Wells D, SenGupta S B. Regionally clustered APC mutations are associated with a severe phenotype and occur at a high frequency in new mutation cases of adenomatous polyposis coli.  Hum Mol Genet . 1994;  3 53-56
    PubMedSearch in Google Scholar
  • 32 Friedl W, Caspari R, Sengteller M. Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis?.  <~>Experience from 680 FAP families. Gut . 2001;  48 515-521
    PubMedSearch in Google Scholar
  • 33 Lynch H T, Smyrk T, McGinn T. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP.  Cancer . 1995;  76 2427-2433
    CrossrefPubMedSearch in Google Scholar
  • 34 Traboulsi E I, Krush A J, Gardner E J. Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome.  N Engl J Med . 1987;  316 661-667
    PubMedSearch in Google Scholar
  • 35 Giardiello F M, Offerhaus G JA, Krush A J. Risk of hepatoblastoma in familial adenomatous polyposis.  J Pediatr . 1991;  119 766-768
    PubMedSearch in Google Scholar
  • 36 Romania A, Zakov N, Church J, Jagelman D G. Retinal pigment epithelium lesions as a biomarker of disease in patients with familial adenomatous polyposis.  Ophthalmology . 1992;  99 911-913
    PubMedSearch in Google Scholar
  • 37 Hamilton S R, Liu B, Parson R E. The molecular basis of Turcot's syndrome.  N Engl J Med . 1995;  332 839-847
    CrossrefPubMedSearch in Google Scholar
  • 38 Matsui T, Hayashi N, Yao K. A father and son with Turcot's syndrome: evidence for autosomal dominant inheritance: report of two cases.  Dis Colon Rectum . 1998;  41 797-801
    PubMedSearch in Google Scholar
  • 39 Goodman A A. Polypoid diseases. In: Corman ML, ed. Colon and Rectal Surgery Philadelphia, PA: Lippincott-Raven 1998: 607-616
    Search in Google Scholar
  • 40 Nivatvongs S. Benign neoplasms of the colon and rectum. In: Gordon PH, Nivatvongs S, eds. Principles and Practice of Surgery for the Colon, Rectum and Anus St. Louis, MO: Quality Medical 1999: 554-569
    Search in Google Scholar
  • 41 Winawer S J, Fletcher R H, Miller L. Colorectal cancer screeing: clinical guidelines and rationale (corrections in Gastroenterology 1997; 112:1060 and 1998;114:625).  Gastroenterology . 1997;  112 594-642
    CrossrefPubMedSearch in Google Scholar
  • 42 Nugent K P, Phillips R KS. Rectal cancer risk in older patients with familial adenomatous polyposis and an ileorectal anastomosis: a cause for concern.  Br J Surg . 1992;  79 1204-1206
    CrossrefPubMedSearch in Google Scholar
  • 43 Heiskanen I, Jarvinen H J. Fate of the rectal stump after colectomy and ileorectal anastomosis for familial adenomatous polyposis.  Int J Colorect Dis . 1997;  12 9-13
    CrossrefPubMedSearch in Google Scholar
  • 44 Bess M A, Adson M A, Elveback L R, Moertal C G. Rectal cancer following colectomy for polyposis.  Arch Surg . 1980;  115 460-467
    PubMedSearch in Google Scholar
  • 45 Decosse J J, Bulow S, Neale K. Rectal cancer risk in patient treated for familial adenomatous polyposis.  Br J Surg . 1992;  79 1372-1375
    PubMedSearch in Google Scholar
  • 46 Wu J S, Paul P, McGannon E A, Church J M. APC genotype, polyp number, and surgical options in familial adenomatosis polyposis.  Ann Surg . 1998;  227 57-62
    CrossrefPubMedSearch in Google Scholar
  • 47 Bertario L, Russo A, Radice P. Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis.  Ann Surg . 2000;  231 538-543
    CrossrefPubMedSearch in Google Scholar
  • 48 Duijvendijk P V, Slors J FM, Taat C W. Functional outcome after colectomy and ileorectal anastomosis compared with proctocolectomy and ileal pouch-anal anastomosis in familial adenomatous polyposis.  Ann Surg . 1999;  230 648-654
    CrossrefPubMedSearch in Google Scholar
  • 49 Nyam D C, Brillant P T, Dozois R R. Ileal pouch-anal canal anastomosis for familial adenomatous polyposis: early and late results.  Ann Surg . 1997;  226 514-521
    CrossrefPubMedSearch in Google Scholar
  • 50 Penna C, Tiret E, Daude F, Parc R. Results of ileal pouch-anal anastomosis in familial adenomatous polyposis complicated by rectal carcinoma.  Dis Colon Rectum . 1994;  37 157-160
    PubMedSearch in Google Scholar
  • 51 Ambroze W L, Dozois R R, Pemberton J H. Familial adenomatous polyposis: results following ileal pouch-anal anastomosis and ileorectostomy.  Dis Colon Rectum . 1992;  35 12-15
    PubMedSearch in Google Scholar
  • 52 Kartheuser A H, Parc R, Penna C P. Ileal pouch-anal anastomosis as the first choice operation in patients with familial adenomatous polyposis: a ten year experience.  Surgery . 1996;  119 615-623
    PubMedSearch in Google Scholar
  • 53 Hoehner J C, Metcalf A M. Development of an invasive adenocarcinoma following colectomy with ileoanal anastomosis for familial polyposis coli: report of a case.  Dis Colon Rectum . 1994;  37 824-828
    PubMedSearch in Google Scholar
  • 54 Malassagne B, Penna C, Parc R. Adenomatous polyps in the anal transition zone after ileal pouch-anal anastomosis for familial adenomatous polyposis: treatment by transanal mucosectomy and ileal pouch advancement.  B J Surg . 1995;  82 1634
    PubMedSearch in Google Scholar
  • 55 Ziv Y, Church J M, Oakley J R. Surgery for the teenager with familial adenomatous polyposis: ileal-rectal anastomosis or restorative proctocolectomy?.  Int J Colorect Dis . 1995;  10 6-9
    CrossrefPubMedSearch in Google Scholar
  • 56 Setti-Carraro P, Nicholls R J. Choice of prophylactic surgery for the large bowel component of familial adenomatous polyposis.  Br J Surg . 1996;  83 885-892
    CrossrefPubMedSearch in Google Scholar
  • 57 Slors J FM, Ponson A E, Taat C W, Bosma A. Risk of residual rectal mucosa after proctocolectomy and ileal pouch-anal reconstruction with the double-stapling technique. Postoperative endoscopic follow-up study.  Dis Colon Rectum . 1995;  38 207-210
    PubMedSearch in Google Scholar
  • 58 Gemlo B T, Belmonte C, Wiltz O, Madoff R D. Functional assessment of ileal pouch-anal anastomotic techniques.  Am J Surg . 1995;  169 137-142
    CrossrefPubMedSearch in Google Scholar
  • 59 Seow-Choen A T, Nicholls R J. Prospective randomized trial comparing anal function after hand sewn ileoanal anastomosis with mucosectomy versus stapled ileoanal anastomosis without mucosectomy in restorative proctocolectomy.  Br J Surg . 1991;  78 430-434
    CrossrefPubMedSearch in Google Scholar
  • 60 Luukkonen P, Jarvinen H. Stapled versus hand-sutured ileoanal anastomosis in restorative proctocolectomy.  Arch Surg . 1993;  128 437-440
    PubMedSearch in Google Scholar
  • 61 Park J G, Park K Y, Ahn Y o. Risk of gastric cancer among Korean familial adenomatous polyposis patients. Report of three cases.  Dis Colon Rectum . 1992;  35 996-998
    CrossrefPubMedSearch in Google Scholar
  • 62 Wallace M H, Phillips R KS. Preventative strategies for periampullary tumors in FAP.  Ann Oncol . 1999;  10 S201-S203
    CrossrefPubMedSearch in Google Scholar
  • 63 Heiskanen I, Kellokumpu I, Jarvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis.  Endoscopy . 1999;  31 412-416
    Thieme ConnectPubMedSearch in Google Scholar
  • 64 Offerhaus G JA, Giardiello F M, Krush A J. The risk of upper gastrointestinal cancer in familial adenomatous polyposis.  Gastroenterology . 1992;  102 1980-1982
    PubMedSearch in Google Scholar
  • 65 Milkvy P. Photodynamic therapy for polyposis in familial adenomatous polyposis.  Eur J Cancer . 1995;  31A 1160-1165
    PubMedSearch in Google Scholar
  • 66 Penna C, Phillips R KS, Tiret E, Spigelman A D. Surgical polypectomy of duodenal adenomas in familial adenomatous polyposis: experience of two European centres.  Br J Surg . 1993;  80 1027-1029
    CrossrefPubMedSearch in Google Scholar
  • 67 Penna C, Bataille N, Balladur P. Surgical treatment of severe duodenal polyposis in familial adenomatous polyposis.  Br J Surg . 1998;  85 665-668
    CrossrefPubMedSearch in Google Scholar
  • 68 Soravia C, Berk T, Haber G. Management of advanced duodenal polyposis in familial adenomatous polyposis.  J Gastrointest Surg . 1997;  1 474-478
    CrossrefPubMedSearch in Google Scholar
  • 69 Gurbuz A K, Giardiello F M, Petersen G M. Desmoid tumours in familial adenomatous polyposis.  Gut . 1994;  35 377-381
    CrossrefPubMedSearch in Google Scholar
  • 70 Lofti A M, Dozois R R, Gordon H. Mesenteric fibromatosis complicating familial adenomatosis polyposis: predisposing factors and results of treatment.  Int J Colorectal Dis . 1989;  4 30-36
    CrossrefPubMedSearch in Google Scholar
  • 71 Penna C, Tiret E, Parc R. Operation and abdominal desmoid tumors in familial adenomatous polyposis.  Surg Gyn Obstet . 1993;  177 263-268
    PubMedSearch in Google Scholar
  • 72 Rodriguez-Bigas M A, Mahoney M C, Karakousis C P, Petrelli N J. Desmoid tumors in patients with familial adenomatous polyposis.  Cancer . 1994;  74 1270-1274
    PubMedSearch in Google Scholar
  • 73 Berk T, Cohen Z, McLeod R S, Stern H. Management of mesenteric desmoid tumours in familial adenomatous polyposis.  Can J Surg . 1992;  35 393-395
    PubMedSearch in Google Scholar
  • 74 Chatzipetrou M A, Tzakis A G, Pinna A D. Intestinal transplantation for the treatment of desmoid tumors associated with familial adenomatosis polyposis.  Surgery . 2001;  129 277-281
    CrossrefPubMedSearch in Google Scholar
  • 75 Giardiello F M, Hamilton S R, Krush A J. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis.  N Engl J Med . 1993;  328 1313-1316
    CrossrefPubMedSearch in Google Scholar
  • 76 Steinbach G, Lynch P M, Phillips R KS. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.  N Engl J Med . 2000;  342 1946-1952
    CrossrefPubMedSearch in Google Scholar
  • 77 Niv Y, Fraser G M. Adenocarcinoma in the rectal segment in familial polyposis coli is not prevented by sulindac therapy.  Gastroenterology . 1994;  107 854-857
    PubMedSearch in Google Scholar
  • 78 Richard C S, Berk T, Bapat B V. Sulindac for periampullary polyps in FAP patients.  Int J Colorect Dis . 1997;  12 14-18
    PubMedSearch in Google Scholar
  • 79 Bapat B, Noorani H, Cohen Z. Cost comparison of predictive genetic testing versus conventional clinical screening for familial adenomatous polyposis.  Gut . 1999;  44 698-703
    PubMedSearch in Google Scholar
  • 80 Berk T, Cohen Z, Bapat B, Gallinger S. Negative genetic test result in familial adenomatous polyposis. Clinical screening implications.  Dis Colon Rectum . 1999;  42 307-312
    CrossrefPubMedSearch in Google Scholar
  • 81 Vasen H FA, Griffioen G, Offerhaus G JA. The value of screening and central registration of families with familial adenomatous polyposis. A study of 82 families in the Netherlands.  Dis Colon Rectum . 1990;  33 227-230
    PubMedSearch in Google Scholar