Download PDF
Clin Colon Rectal Surg 2008; 21(4): 263-272
DOI: 10.1055/s-0028-1089941
© Thieme Medical Publishers

Extracolonic Manifestations of Hereditary Colorectal Cancer Syndromes

Daniel A. Anaya1 , George J. Chang1 , Miguel A. Rodriguez-Bigas1
  • 1Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Further Information

Publication History

Publication Date:
14 October 2008 (online)

    Permissions and Reprints

ABSTRACT

Familial colorectal adenocarcinoma (CRC) accounts for ~15 to 20% of CRC. Of these, hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) represent the most common hereditary syndromes associated with CRC, followed by other less common diseases including juvenile polyposis (JP) and Peutz–Jeghers syndrome (PJS). Extracolonic manifestations are common in each of these syndromes having significant implications for surveillance and management in at-risk individuals. The authors review the most common and clinically relevant extracolonic manifestations for each of these syndromes focusing on incidence, presentation, genotype/phenotype correlations, and management (including surveillance) strategies.

KEYWORDS

Hereditary polyposis - colorectal cancer - extracolonic manifestations

REFERENCES

  • 1 Rodriguez-Bigas M A, Chang G J, Skibber J M. Surgical implications of colorectal cancer genetics.  Surg Oncol Clin N Am. 2006;  15(1) 51-66 , vi
    CrossrefPubMedGoogle Scholar
  • 2 Guillem J G, Wood W C, Moley J F et al.. ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes.  J Clin Oncol. 2006;  24(28) 4642-4660
    CrossrefPubMedGoogle Scholar
  • 3 Burt R, Neklason D W. Genetic testing for inherited colon cancer.  Gastroenterology. 2005;  128(6) 1696-1716
    CrossrefPubMedGoogle Scholar
  • 4 Bussey H J. Familial polyposis coli: family studies, histopathology, differential diagnosis, and results of treatment. Baltimore; The Johns Hopkins University Press 1975
    Google Scholar
  • 5 Brosens L A, van Hattem W A, Jansen M et al.. Gastrointestinal polyposis syndromes.  Curr Mol Med. 2007;  7(1) 29-46
    CrossrefPubMedGoogle Scholar
  • 6 Nugent K P, Spigelman A D, Phillips R K. Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis.  Dis Colon Rectum. 1993;  36(11) 1059-1062
    PubMedGoogle Scholar
  • 7 Bertario L, Presciuttini S, Sala P et al.. Causes of death and postsurgical survival in familial adenomatous polyposis: results from the Italian Registry. Italian Registry of Familial Polyposis Writing Committee.  Semin Surg Oncol. 1994;  10(3) 225-234
    CrossrefPubMedGoogle Scholar
  • 8 Nagase H, Nakamura Y. Mutations of the APC (adenomatous polyposis coli) gene.  Hum Mutat. 1993;  2(6) 425-434
    CrossrefPubMedGoogle Scholar
  • 9 Caspari R, Olschwang S, Friedl W et al.. Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444.  Hum Mol Genet. 1995;  4(3) 337-340
    PubMedGoogle Scholar
  • 10 Caspari R, Friedl W, Mandl M et al.. Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer.  Lancet. 1994;  343(8898) 629-632
    CrossrefPubMedGoogle Scholar
  • 11 Bertario L, Russo A, Sala P et al.. Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis.  Int J Cancer. 2001;  95(2) 102-107
    CrossrefPubMedGoogle Scholar
  • 12 Olschwang S, Tiret A, Laurent-Puig P et al.. Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients.  Cell. 1993;  75(5) 959-968
    CrossrefPubMedGoogle Scholar
  • 13 Spirio L, Olschwang S, Groden J et al.. Alleles of the APC gene: an attenuated form of familial polyposis.  Cell. 1993;  75(5) 951-957
    CrossrefPubMedGoogle Scholar
  • 14 Soravia C, Berk T, Madlensky L et al.. Genotype-phenotype correlations in attenuated adenomatous polyposis coli.  Am J Hum Genet. 1998;  62(6) 1290-1301
    CrossrefPubMedGoogle Scholar
  • 15 Vasen H F, van der Luijt R B, Slors J F et al.. Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis.  Lancet. 1996;  348(9025) 433-435
    CrossrefPubMedGoogle Scholar
  • 16 Wu J S, Paul P, McGannon E A, Church J M. APC genotype, polyp number, and surgical options in familial adenomatous polyposis.  Ann Surg. 1998;  227(1) 57-62
    CrossrefPubMedGoogle Scholar
  • 17 Bertario L, Russo A, Radice P et al.. Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis. Hereditary Colorectal Tumors Registry.  Ann Surg. 2000;  231(4) 538-543
    CrossrefPubMedGoogle Scholar
  • 18 Jarvinen H J, Peltomaki P. The complex genotype-phenotype relationship in familial adenomatous polyposis.  Eur J Gastroenterol Hepatol. 2004;  16(1) 5-8
    CrossrefPubMedGoogle Scholar
  • 19 Bisgaard M L, Bulow S. Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with osteomas and sebaceous cysts.  Am J Med Genet A. 2006;  140(3) 200-204
    PubMedGoogle Scholar
  • 20 Cetta F, Curia M C, Montalto G et al.. Thyroid carcinoma usually occurs in patients with familial adenomatous polyposis in the absence of biallelic inactivation of the adenomatous polyposis coli gene.  J Clin Endocrinol Metab. 2001;  86(1) 427-432
    CrossrefPubMedGoogle Scholar
  • 21 Gallagher M C, Phillips R K, Bulow S. Surveillance and management of upper gastrointestinal disease in familial adenomatous polyposis.  Fam Cancer. 2006;  5(3) 263-273
    CrossrefPubMedGoogle Scholar
  • 22 Offerhaus G J, Giardiello F M, Krush A J et al.. The risk of upper gastrointestinal cancer in familial adenomatous polyposis.  Gastroenterology. 1992;  102(6) 1980-1982
    PubMedGoogle Scholar
  • 23 Park J G, Park K J, Ahn Y O et al.. Risk of gastric cancer among Korean familial adenomatous polyposis patients. Report of three cases.  Dis Colon Rectum. 1992;  35(10) 996-998
    CrossrefPubMedGoogle Scholar
  • 24 Wallace M H, Phillips R K. Upper gastrointestinal disease in patients with familial adenomatous polyposis.  Br J Surg. 1998;  85(6) 742-750
    CrossrefPubMedGoogle Scholar
  • 25 Brosens L A, Keller J J, Offerhaus G J et al.. Prevention and management of duodenal polyps in familial adenomatous polyposis.  Gut. 2005;  54(7) 1034-1043
    CrossrefPubMedGoogle Scholar
  • 26 Bulow S, Bjork J, Christensen I J et al.. Duodenal adenomatosis in familial adenomatous polyposis.  Gut. 2004;  53(3) 381-386
    CrossrefPubMedGoogle Scholar
  • 27 Jagelman D G, DeCosse J J, Bussey H J. Upper gastrointestinal cancer in familial adenomatous polyposis.  Lancet. 1988;  1(8595) 1149-1151
    PubMedGoogle Scholar
  • 28 Bjork J, Akerbrant H, Iselius L et al.. Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations.  Gastroenterology. 2001;  121(5) 1127-1135
    CrossrefPubMedGoogle Scholar
  • 29 Galle T S, Juel K, Bulow S. Causes of death in familial adenomatous polyposis.  Scand J Gastroenterol. 1999;  34(8) 808-812
    CrossrefPubMedGoogle Scholar
  • 30 Spigelman A D, Williams C B, Talbot I C et al.. Upper gastrointestinal cancer in patients with familial adenomatous polyposis.  Lancet. 1989;  2(8666) 783-785
    PubMedGoogle Scholar
  • 31 Heiskanen I, Kellokumpu I, Jarvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis.  Endoscopy. 1999;  31(6) 412-416
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Moozar K L, Madlensky L, Berk T, Gallinger S. Slow progression of periampullary neoplasia in familial adenomatous polyposis.  J Gastrointest Surg. 2002;  6(6) 831-837 discussion 837
    CrossrefPubMedGoogle Scholar
  • 33 Groves C J, Saunders B P, Spigelman A D, Phillips R K. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study.  Gut. 2002;  50(5) 636-641
    CrossrefPubMedGoogle Scholar
  • 34 Bertario L, Russo A, Sala P et al.. Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis.  J Clin Oncol. 2003;  21(9) 1698-1707
    CrossrefPubMedGoogle Scholar
  • 35 Groves C, Lamlum H, Crabtree M et al.. Mutation cluster region, association between germline and somatic mutations and genotype-phenotype correlation in upper gastrointestinal familial adenomatous polyposis.  Am J Pathol. 2002;  160(6) 2055-2061
    PubMedGoogle Scholar
  • 36 Gurbuz A K, Giardiello F M, Petersen G M et al.. Desmoid tumours in familial adenomatous polyposis.  Gut. 1994;  35(3) 377-381
    CrossrefPubMedGoogle Scholar
  • 37 Clark S K, Phillips R K. Desmoids in familial adenomatous polyposis.  Br J Surg. 1996;  83(11) 1494-1504
    CrossrefPubMedGoogle Scholar
  • 38 Soravia C, Berk T, McLeod R S, Cohen Z. Desmoid disease in patients with familial adenomatous polyposis.  Dis Colon Rectum. 2000;  43(3) 363-369
    CrossrefPubMedGoogle Scholar
  • 39 Anthony T, Rodriguez-Bigas M A, Weber T K, Petrelli N J. Desmoid tumors.  J Am Coll Surg. 1996;  182(4) 369-377
    PubMedGoogle Scholar
  • 40 Nieuwenhuis M H, De Vos Tot Nederveen Cappel W, Botma A et al.. Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis.  Clin Gastroenterol Hepatol. 2008;  6(2) 215-219
    CrossrefPubMedGoogle Scholar
  • 41 Church J, Berk T, Boman B M et al.. Staging intra-abdominal desmoid tumors in familial adenomatous polyposis: a search for a uniform approach to a troubling disease.  Dis Colon Rectum. 2005;  48(8) 1528-1534
    CrossrefPubMedGoogle Scholar
  • 42 Berk T, Cohen Z, McLeod R S, Stern H S. Management of mesenteric desmoid tumours in familial adenomatous polyposis.  Can J Surg. 1992;  35(4) 393-395
    PubMedGoogle Scholar
  • 43 Rodriguez-Bigas M A, Mahoney M C, Karakousis C P, Petrelli N J. Desmoid tumors in patients with familial adenomatous polyposis.  Cancer. 1994;  74(4) 1270-1274
    PubMedGoogle Scholar
  • 44 Clark S K, Smith T G, Katz D E et al.. Identification and progression of a desmoid precursor lesion in patients with familial adenomatous polyposis.  Br J Surg. 1998;  85(7) 970-973
    CrossrefPubMedGoogle Scholar
  • 45 Middleton S B, Clark S K, Matravers P et al.. Stepwise progression of familial adenomatous polyposis-associated desmoid precursor lesions demonstrated by a novel CT scoring system.  Dis Colon Rectum. 2003;  46(4) 481-485
    CrossrefPubMedGoogle Scholar
  • 46 Healy J C, Reznek R H, Clark S K et al.. MR appearances of desmoid tumors in familial adenomatous polyposis.  AJR Am J Roentgenol. 1997;  169(2) 465-472
    PubMedGoogle Scholar
  • 47 Gega M, Yanagi H, Yoshikawa R et al.. Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis.  J Clin Oncol. 2006;  24(1) 102-105
    CrossrefPubMedGoogle Scholar
  • 48 Heinrich M C, McArthur G A, Demetri G D et al.. Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor).  J Clin Oncol. 2006;  24(7) 1195-1203
    CrossrefPubMedGoogle Scholar
  • 49 Friedl W, Caspari R, Sengteller M et al.. Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families.  Gut. 2001;  48(4) 515-521
    PubMedGoogle Scholar
  • 50 Giardiello F M, Offerhaus G J, Lee D H et al.. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis.  Gut. 1993;  34(10) 1394-1396
    CrossrefPubMedGoogle Scholar
  • 51 Traboulsi E I. Familial adenomatous polyposis.  Dis Colon Rectum. 1989;  32(7) 633-634
    CrossrefPubMedGoogle Scholar
  • 52 Giardiello F M, Offerhaus G J, Traboulsi E I et al.. Value of combined phenotypic markers in identifying inheritance of familial adenomatous polyposis.  Gut. 1991;  32(10) 1170-1174
    CrossrefPubMedGoogle Scholar
  • 53 Gardner E J. Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas, fibromas and epidermal cysts.  Am J Hum Genet. 1962;  14 376-390
    PubMedGoogle Scholar
  • 54 Lynch H T, Smyrk T C, Lanspa S J et al.. Upper gastrointestinal manifestations in families with hereditary flat adenoma syndrome.  Cancer. 1993;  71(9) 2709-2714
    CrossrefPubMedGoogle Scholar
  • 55 Lynch H T, Smyrk T, McGinn T et al.. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP.  Cancer. 1995;  76(12) 2427-2433
    CrossrefPubMedGoogle Scholar
  • 56 Hernegger G S, Moore H G, Guillem J G. Attenuated familial adenomatous polyposis: an evolving and poorly understood entity.  Dis Colon Rectum. 2002;  45(1) 127-134 discussion 134-136
    CrossrefPubMedGoogle Scholar
  • 57 Knudsen A L, Bisgaard M L, Bulow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature.  Fam Cancer. 2003;  2(1) 43-55
    CrossrefPubMedGoogle Scholar
  • 58 Sieber O M, Lipton L, Crabtree M et al.. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.  N Engl J Med. 2003;  348(9) 791-799
    CrossrefPubMedGoogle Scholar
  • 59 Vasen H F, Moslein G, Alonso A et al.. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer).  J Med Genet. 2007;  44(6) 353-362
    CrossrefPubMedGoogle Scholar
  • 60 Vasen H F. Clinical description of the Lynch syndrome [hereditary nonpolyposis colorectal cancer (HNPCC)].  Fam Cancer. 2005;  4(3) 219-225
    CrossrefPubMedGoogle Scholar
  • 61 Lindor N M, Petersen G M, Hadley D W et al.. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review.  JAMA. 2006;  296(12) 1507-1517
    CrossrefPubMedGoogle Scholar
  • 62 Umar A, Boland C R, Terdiman J P et al.. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability.  J Natl Cancer Inst. 2004;  96(4) 261-268
    CrossrefPubMedGoogle Scholar
  • 63 Vasen H F, Mecklin J P, Khan P M, Lynch H T. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC).  Dis Colon Rectum. 1991;  34(5) 424-425
    PubMedGoogle Scholar
  • 64 Aarnio M, Mecklin J P, Aaltonen L A et al.. Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome.  Int J Cancer. 1995;  64(6) 430-433
    CrossrefPubMedGoogle Scholar
  • 65 Dunlop M G, Farrington S M, Carothers A D et al.. Cancer risk associated with germline DNA mismatch repair gene mutations.  Hum Mol Genet. 1997;  6(1) 105-110
    CrossrefPubMedGoogle Scholar
  • 66 Watson P, Vasen H F, Mecklin J P et al.. The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer.  Am J Med. 1994;  96(6) 516-520
    CrossrefPubMedGoogle Scholar
  • 67 Wijnen J, de Leeuw W, Vasen H et al.. Familial endometrial cancer in female carriers of MSH6 germline mutations.  Nat Genet. 1999;  23(2) 142-144
    CrossrefPubMedGoogle Scholar
  • 68 Lin K M, Shashidharan M, Ternent C A et al.. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population.  Dis Colon Rectum. 1998;  41(4) 428-433
    CrossrefPubMedGoogle Scholar
  • 69 Hendriks Y M, Wagner A, Morreau H et al.. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance.  Gastroenterology. 2004;  127(1) 17-25
    CrossrefPubMedGoogle Scholar
  • 70 Dove-Edwin I, Boks D, Goff S et al.. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma.  Cancer. 2002;  94(6) 1708-1712
    CrossrefPubMedGoogle Scholar
  • 71 Rijcken F E, Mourits M J, Kleibeuker J H et al.. Gynecologic screening in hereditary nonpolyposis colorectal cancer.  Gynecol Oncol. 2003;  91(1) 74-80
    CrossrefPubMedGoogle Scholar
  • 72 Renkonen-Sinisalo L, Butzow R, Leminen A et al.. Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome.  Int J Cancer. 2007;  120(4) 821-824
    CrossrefPubMedGoogle Scholar
  • 73 Schmeler K M, Lynch H T, Chen L M et al.. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome.  N Engl J Med. 2006;  354(3) 261-269
    CrossrefPubMedGoogle Scholar
  • 74 Wirtzfeld D A, Petrelli N J, Rodriguez-Bigas M A. Hamartomatous polyposis syndromes: molecular genetics, neoplastic risk, and surveillance recommendations.  Ann Surg Oncol. 2001;  8(4) 319-327
    CrossrefPubMedGoogle Scholar
  • 75 Desai D C, Neale K F, Talbot I C et al.. Juvenile polyposis.  Br J Surg. 1995;  82(1) 14-17
    CrossrefPubMedGoogle Scholar
  • 76 Handra-Luca A, Condroyer C, de Moncuit C et al.. Vessels' morphology in SMAD4 and BMPR1A-related juvenile polyposis.  Am J Med Genet A. 2005;  138(2) 113-117
    PubMedGoogle Scholar
  • 77 Brosens L A, van Hattem A, Hylind L M et al.. Risk of colorectal cancer in juvenile polyposis.  Gut. 2007;  56(7) 965-967
    CrossrefPubMedGoogle Scholar
  • 78 Howe J R, Mitros F A, Summers R W. The risk of gastrointestinal carcinoma in familial juvenile polyposis.  Ann Surg Oncol. 1998;  5(8) 751-756
    CrossrefPubMedGoogle Scholar
  • 79 McGrath D R, Spigelman A D. Preventive measures in Peutz-Jeghers syndrome.  Fam Cancer. 2001;  1(2) 121-125
    PubMedGoogle Scholar
  • 80 McGarrity T J, Kulin H E, Zaino R J. Peutz-Jeghers syndrome.  Am J Gastroenterol. 2000;  95(3) 596-604
    CrossrefPubMedGoogle Scholar
  • 81 Vogel T, Schumacher V, Saleh A et al.. Extraintestinal polyps in Peutz-Jeghers syndrome: presentation of four cases and review of the literature. Deutsche Peutz-Jeghers-Studiengruppe.  Int J Colorectal Dis. 2000;  15(2) 118-123
    CrossrefPubMedGoogle Scholar
  • 82 Giardiello F M, Trimbath J D. Peutz-Jeghers syndrome and management recommendations.  Clin Gastroenterol Hepatol. 2006;  4(4) 408-415
    CrossrefPubMedGoogle Scholar
  • 83 Utsunomiya J, Gocho H, Miyanaga T et al.. Peutz-Jeghers syndrome: its natural course and management.  Johns Hopkins Med J. 1975;  136(2) 71-82
    PubMedGoogle Scholar
  • 84 Giardiello F M, Brensinger J D, Tersmette A C et al.. Very high risk of cancer in familial Peutz-Jeghers syndrome.  Gastroenterology. 2000;  119(6) 1447-1453
    CrossrefPubMedGoogle Scholar
  • 85 Lim W, Olschwang S, Keller J J et al.. Relative frequency and morphology of cancers in STK11 mutation carriers.  Gastroenterology. 2004;  126(7) 1788-1794
    CrossrefPubMedGoogle Scholar
  • 86 Dunlop M G. Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome.  Gut. 2002;  51(Suppl 5) V21-V27
    CrossrefPubMedGoogle Scholar
  • 87 Oncel M, Remzi F H, Church J M et al.. Benefits of ‘clean sweep’ in Peutz-Jeghers patients.  Colorectal Dis. 2004;  6(5) 332-335
    CrossrefPubMedGoogle Scholar

George J ChangM.D. 

Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center

1515 Holcombe Blvd., Unit 444, P.O. Box 301402, Houston, TX 77230

Email: gchang@mdanderson.org

      >