Inherited Colorectal Cancer Syndromes

ABSTRACT

Colorectal cancer is common in the Western world; ~5% of individuals diagnosed with colorectal cancer have an identifiable inherited genetic predisposition to this malignancy. Genetic testing and rational clinical management recommendations currently exist for the management of individuals with a variety of colorectal cancer syndromes, including hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome), familial adenomatous polyposis (FAP), MYH-associated polyposis (MAP), and the hamartomatous polyposis syndromes (Peutz–Jeghers, juvenile polyposis, and Cowden disease). In addition to colorectal neoplasia, these syndromes frequently predispose carriers to a variety of extracolonic cancers. The elucidation of the genetic basis of several colorectal cancer predisposition syndromes over the past two decades has allowed for better management of individuals who are either affected with, or at-risk for inherited colorectal cancer syndromes. Appropriate multidisciplinary management of these individuals includes genetic counseling, genetic testing, clinical screening, and treatment recommendations.

KEYWORDS

Colorectal cancer - hereditary nonpolyposis colorectal cancer - familial adenomatous polyposis - hamartomatous polyps

REFERENCES

• 1 Burt R, Neklason D W. Genetic testing for inherited colon cancer.  Gastroenterology. 2005;  128(6) 1696-1716
• 2 de la Chapelle A. Genetic predisposition to colorectal cancer.  Nat Rev Cancer. 2004;  4(10) 769-780
• 3 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
• 4 Hampel H, Stephens J A, Pukkala E et al.. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset.  Gastroenterology. 2005;  129(2) 415-421
• 5 Rodriguez-Bigas M A, Boland C R, Hamilton S R et al.. A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda Guidelines.  J Natl Cancer Inst. 1997;  89 1758-1762
• 6 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
• 7 Hamilton S R, Liu B, Parsons R E et al.. The molecular basis of Turcot's syndrome.  N Engl J Med. 1995;  332(13) 839-847
• 8 Ponti G, Ponz de Leon M. Muir-Torre syndrome.  Lancet Oncol. 2005;  6(12) 980-987
• 9 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
• 10 Gryfe R, Kim H, Hsieh E T et al.. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer.  N Engl J Med. 2000;  342(2) 69-77
• 11 Kim H, Jen J, Vogelstein B, Hamilton S R. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences.  Am J Pathol. 1994;  145(1) 148-156
• 12 Aaltonen L A, Peltomäki P, Leach F S et al.. Clues to the pathogenesis of familial colorectal cancer.  Science. 1993;  260(5109) 812-816
• 13 Kinzler K W, Vogelstein B. Lessons from hereditary colorectal cancer.  Cell. 1996;  87(2) 159-170
• 14 Peltomäki P, Vasen H. Mutations associated with HNPCC predisposition—Update of ICG-HNPCC/INSiGHT mutation database.  Dis Markers. 2004;  20(4-5) 269-276
• 15 Ionov Y, Peinado M A, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis.  Nature. 1993;  363(6429) 558-561
• 16 Thibodeau S N, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon.  Science. 1993;  260(5109) 816-819
• 17 Boland C R, Thibodeau S N, Hamilton S R et al.. A National Cancer Institute Workshop on Microsatellite Instability for Cancer Detection and Familial Predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer.  Cancer Res. 1998;  58 5248-5257
• 18 Ricciardone M D, Ozçelik T, Cevher B et al.. Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1.  Cancer Res. 1999;  59(2) 290-293
• 19 Bandipalliam P. Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations.  Fam Cancer. 2005;  4(4) 323-333
• 20 Kane M F, Loda M, Gaida G M et al.. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.  Cancer Res. 1997;  57(5) 808-811
• 21 Gill S, Lindor N M, Burgart L J et al.. Isolated loss of PMS2 expression in colorectal cancers: frequency, patient age, and familial aggregation.  Clin Cancer Res. 2005;  11(18) 6466-6471
• 22 Hampel H, Frankel W L, Martin E et al.. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).  N Engl J Med. 2005;  352(18) 1851-1860
• 23 American Society of Clinical Oncology . American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.  J Clin Oncol. 2003;  21(12) 2397-2406
• 24 Nyström-Lahti M, Kristo P, Nicolaides N C et al.. Founding mutations and Alu-mediated recombination in hereditary colon cancer.  Nat Med. 1995;  1(11) 1203-1206
• 25 Gille J J, Hogervorst F B, Pals G et al.. Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach.  Br J Cancer. 2002;  87(8) 892-897
• 26 Raevaara T E, Korhonen M K, Lohi H et al.. Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1.  Gastroenterology. 2005;  129(2) 537-549
• 27 Aaltonen L A, Salovaara R, Kristo P et al.. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease.  N Engl J Med. 1998;  338(21) 1481-1487
• 28 Hampel H, Frankel W L, Martin E et al.. Feasibility of screening for Lynch syndrome among patients with colorectal cancer.  J Clin Oncol. 2008;  26(35) 5783-5788
• 29 Barnetson R A, Tenesa A, Farrington S M et al.. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer.  N Engl J Med. 2006;  354(26) 2751-2763
• 30 de Vos tot Nederveen Cappel W H, Nagengast F M, Griffioen G et al.. Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families.  Dis Colon Rectum. 2002;  45(12) 1588-1594
• 31 Winawer S, Fletcher R, Rex D Gastrointestinal Consortium Panel et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale-update based on new evidence.  Gastroenterology. 2003;  124(2) 544-560
• 32 Järvinen H J, Aarnio M, Mustonen H et al.. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer.  Gastroenterology. 2000;  118(5) 829-834
• 33 Burke W, Petersen G, Lynch P et al.. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium.  JAMA. 1997;  277(11) 915-919
• 34 Guillem J G, Wood W C, Moley J F ASCO 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
• 35 Church J, Simmang C. Standards Task Force . Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer).  Dis Colon Rectum. 2003;  46(8) 1001-1012
• 36 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
• 37 Popat S, Hubner R, Houlston R S. Systematic review of microsatellite instability and colorectal cancer prognosis.  J Clin Oncol. 2005;  23(3) 609-618
• 38 Sankila R, Aaltonen L A, Järvinen H J, Mecklin J P. Better survival rates in patients with MLH1-associated hereditary colorectal cancer.  Gastroenterology. 1996;  110(3) 682-687
• 39 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
• 40 Bertario L, Russo A, Sala P et al.. Survival of patients with hereditary colorectal cancer: comparison of HNPCC and colorectal cancer in FAP patients with sporadic colorectal cancer.  Int J Cancer. 1999;  80(2) 183-187
• 41 Ribic C M, Sargent D J, Moore M J et al.. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer.  N Engl J Med. 2003;  349(3) 247-257
• 42 Barratt P L, Seymour M T, Stenning S P UKCCCR AXIS trial collaborators. Adjuvant X-ray and Fluorouracil Infusion Study et al. DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study.  Lancet. 2002;  360(9343) 1381-1391
• 43 Carethers J M, Smith E J, Behling C A et al.. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer.  Gastroenterology. 2004;  126(2) 394-401
• 44 Jover R, Zapater P, Castells A Gastrointestinal Oncology Group of the Spanish Gastroenterological Association et al. Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer.  Gut. 2006;  55(6) 848-855
• 45 Jover R, Zapater P, Castells A Gastrointestinal Oncology Group of the Spanish Gastroenterological Association et al. The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status.  Eur J Cancer. 2009;  45(3) 365-373
• 46 Halling K C, French A J, McDonnell S K et al.. Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers.  J Natl Cancer Inst. 1999;  91(15) 1295-1303
• 47 Kim G P, Colangelo L H, Wieand H S National Cancer Institute et al. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study.  J Clin Oncol. 2007;  25(7) 767-772
• 48 Bertagnolli M M, Niedzwiecki D, Compton C C et al.. Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803.  J Clin Oncol. 2009;  27(11) 1814-1821
• 49 Lindor N M, Rabe K, Petersen G M et al.. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X.  JAMA. 2005;  293(16) 1979-1985
• 50 Mueller-Koch Y, Vogelsang H, Kopp R et al.. Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer.  Gut. 2005;  54(12) 1733-1740
• 51 Valle L, Perea J, Carbonell P et al.. Clinicopathologic and pedigree differences in Amsterdam I-positive hereditary nonpolyposis colorectal cancer families according to tumor microsatellite instability status.  J Clin Oncol. 2007;  25(7) 781-786
• 52 Ponz de Leon M, Bertario L, Genuardi M et al.. Identification and classification of hereditary nonpolyposis colorectal cancer (Lynch syndrome): adapting old concepts to recent advancements. Report from the Italian Association for the Study of Hereditary Colorectal Tumors Consensus Group.  Dis Colon Rectum. 2007;  50(12) 2126-2134
• 53 Knudsen A L, Bisgaard M L, Bülow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature.  Fam Cancer. 2003;  2(1) 43-55
• 54 King J E, Dozois R R, Lindor N M, Ahlquist D A. Care of patients and their families with familial adenomatous polyposis.  Mayo Clin Proc. 2000;  75(1) 57-67
• 55 Belchetz L A, Berk T, Bapat B V, Cohen Z, Gallinger S. Changing causes of mortality in patients with familial adenomatous polyposis.  Dis Colon Rectum. 1996;  39(4) 384-387
• 56 Kinzler K W, Nilbert M C, Su L K et al.. Identification of FAP locus genes from chromosome 5q21.  Science. 1991;  253(5020) 661-665
• 57 Nishisho I, Nakamura Y, Miyoshi Y et al.. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.  Science. 1991;  253(5020) 665-669
• 58 Fearon E R, Vogelstein B. A genetic model for colorectal tumorigenesis.  Cell. 1990;  61(5) 759-767
• 59 Vogelstein B, Kinzler K W. Cancer genes and the pathways they control.  Nat Med. 2004;  10(8) 789-799
• 60 Powell S M, Zilz N, Beazer-Barclay Y et al.. APC mutations occur early during colorectal tumorigenesis.  Nature. 1992;  359(6392) 235-237
• 61 Laurent-Puig P, Béroud C, Soussi T. APC gene: database of germline and somatic mutations in human tumors and cell lines.  Nucleic Acids Res. 1998;  26(1) 269-270
• 62 Powell S M, Petersen G M, Krush A J et al.. Molecular diagnosis of familial adenomatous polyposis.  N Engl J Med. 1993;  329(27) 1982-1987
• 63 American Gastroenterological Association . American Gastroenterological Association medical position statement: hereditary colorectal cancer and genetic testing.  Gastroenterology. 2001;  121(1) 195-197
• 64 Giardiello F M, Brensinger J D, Petersen G M et al.. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis.  N Engl J Med. 1997;  336(12) 823-827
• 65 Steinbach G, Lynch P M, Phillips R K et al.. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.  N Engl J Med. 2000;  342(26) 1946-1952
• 66 Laken S J, Petersen G M, Gruber S B et al.. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC.  Nat Genet. 1997;  17(1) 79-83
• 67 Gryfe R, Di Nicola N, Gallinger S, Redston M. Somatic instability of the APC I1307K allele in colorectal neoplasia.  Cancer Res. 1998;  58(18) 4040-4043
• 68 Gryfe R, Di Nicola N, Lal G, Gallinger S, Redston M. Inherited colorectal polyposis and cancer risk of the APC I1307K polymorphism.  Am J Hum Genet. 1999;  64(2) 378-384
• 69 Cleary S P, Kim H, Croitoru M E et al.. Missense polymorphisms in the adenomatous polyposis coli gene and colorectal cancer risk.  Dis Colon Rectum. 2008;  51 1467-1473 discussion 1473-1464
• 70 Joint Test and Technology Transfer Committee Working Group . Genetic Testing for Colon Cancer: Joint Statement of the American College of Medical Genetics and American Society of Human Genetics.  Genet Med. 2000;  2(6) 362-366
• 71 Al-Tassan N, Chmiel N H, Maynard J et al.. Inherited variants of MYH associated with somatic G:C—> T:A mutations in colorectal tumors.  Nat Genet. 2002;  30(2) 227-232
• 72 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
• 73 Croitoru M E, Cleary S P, Di Nicola N et al.. Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk.  J Natl Cancer Inst. 2004;  96(21) 1631-1634
• 74 Cleary S P, Cotterchio M, Jenkins M A et al.. Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study.  Gastroenterology. 2009;  136(4) 1251-1260
• 75 Sampson J R, Jones N. MUTYH-associated polyposis.  Best Pract Res Clin Gastroenterol. 2009;  23(2) 209-218
• 76 Hemminki A, Markie D, Tomlinson I et al.. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome.  Nature. 1998;  391(6663) 184-187
• 77 Jenne D E, Reimann H, Nezu J et al.. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.  Nat Genet. 1998;  18(1) 38-43
• 78 Chow E, Macrae F. A review of juvenile polyposis syndrome.  J Gastroenterol Hepatol. 2005;  20(11) 1634-1640
• 79 Howe J R, Roth S, Ringold J C et al.. Mutations in the SMAD4/DPC4 gene in juvenile polyposis.  Science. 1998;  280(5366) 1086-1088
• 80 Howe J R, Bair J L, Sayed M G et al.. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis.  Nat Genet. 2001;  28(2) 184-187
• 81 Gallione C J, Repetto G M, Legius E et al.. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4).  Lancet. 2004;  363(9412) 852-859
• 82 Marsh D J, Dahia P L, Zheng Z et al.. Germline mutations in PTEN are present in Bannayan-Zonana syndrome.  Nat Genet. 1997;  16(4) 333-334
• 83 Liaw D, Marsh D J, Li J et al.. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.  Nat Genet. 1997;  16(1) 64-67
• 84 Kinzler K W, Vogelstein B. Landscaping the cancer terrain.  Science. 1998;  280(5366) 1036-1037