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Clin Colon Rectal Surg 2016; 29(03): 185-195
DOI: 10.1055/s-0036-1584290
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Familial Colorectal Cancer: Understanding the Alphabet Soup

Matthew D. Giglia
1   Division of Gastrointestinal Surgery, University of Alabama at Birmingham, Birmingham, Alabama
,
Daniel I. Chu
1   Division of Gastrointestinal Surgery, University of Alabama at Birmingham, Birmingham, Alabama
› Author Affiliations
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Publication History

Publication Date:
17 August 2016 (online)

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Abstract

While most colorectal cancers (CRCs) originate from nonhereditary spontaneous mutations, one-third of cases are familial or hereditary. Hereditary CRCs, which account for < 5% of all CRCs, have identifiable germline mutations and phenotypes, such as Lynch syndrome and familial adenomatous polyposis (FAP). Familial CRCs, which account for up to 30% of CRCs, have no identifiable germline mutation or specific pattern of inheritance, but higher-than-expected incidence within a family. Since the discovery that certain genotypes can lead to development of CRC, thousands of mutations have now been implicated in CRC. These new findings have enhanced our ability to identify at-risk patients, initiate better surveillance, and take preventative measures. Given the large number of genes now associated with hereditary and familial CRCs, clinicians should be familiar with the alphabet soup of genes to provide the highest quality of care for patients and families.

Keywords

colorectal cancer - hereditary - familial - genetic
 

  • References

  • 1 National Cancer Institute. SEER stat fact sheets: colon and rectum cancer. Available at: http://seer.cancer.gov/statfacts/html/colorect.html . Accessed August 20, 2015
    PubMedGoogle Scholar
  • 2 Bodmer WF, Bailey CJ, Bodmer J , et al. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature 1987; 328 (6131) 614-616
    CrossrefPubMedGoogle Scholar
  • 3 Nagy R, Sweet K, Eng C. Highly penetrant hereditary cancer syndromes. Oncogene 2004; 23 (38) 6445-6470
    CrossrefPubMedGoogle Scholar
  • 4 Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ. Hereditary factors in cancer. Study of two large midwestern kindreds. Arch Intern Med 1966; 117 (2) 206-212
    CrossrefPubMedGoogle Scholar
  • 5 Fishel R, Lescoe MK, Rao MR , et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 1993; 75 (5) 1027-1038
    CrossrefPubMedGoogle Scholar
  • 6 Aarnio M, Mecklin JP, Aaltonen LA, Nyström-Lahti M, Järvinen HJ. Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer 1995; 64 (6) 430-433
    CrossrefPubMedGoogle Scholar
  • 7 Charames GS, Bapat B. Genomic instability and cancer. Curr Mol Med 2003; 3 (7) 589-596
    CrossrefPubMedGoogle Scholar
  • 8 Jacob S, Praz F. DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie 2002; 84 (1) 27-47
    CrossrefPubMedGoogle Scholar
  • 9 Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991; 34 (5) 424-425
    CrossrefPubMedGoogle Scholar
  • 10 Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 1999; 116 (6) 1453-1456
    CrossrefPubMedGoogle Scholar
  • 11 Umar A, Boland CR, Terdiman JP , 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
  • 12 Barzi A, Sadeghi S, Kattan MW, Meropol NJ. Comparative effectiveness of screening strategies for Lynch syndrome. J Natl Cancer Inst 2015; 107 (4)
    PubMedGoogle Scholar
  • 13 Barnetson RA, Tenesa A, Farrington SM , 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
    CrossrefPubMedGoogle Scholar
  • 14 Chen S, Wang W, Lee S , et al; Colon Cancer Family Registry. Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA 2006; 296 (12) 1479-1487
    CrossrefPubMedGoogle Scholar
  • 15 Kastrinos F, Steyerberg EW, Mercado R , et al. The PREMM(1,2,6) model predicts risk of MLH1, MSH2, and MSH6 germline mutations based on cancer history. Gastroenterology 2011; 140 (1) 73-81
    CrossrefPubMedGoogle Scholar
  • 16 Green RC, Parfrey PS, Woods MO, Younghusband HB. Prediction of Lynch syndrome in consecutive patients with colorectal cancer. J Natl Cancer Inst 2009; 101 (5) 331-340
    CrossrefPubMedGoogle Scholar
  • 17 Järvinen HJ, 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
    CrossrefPubMedGoogle Scholar
  • 18 Vasen HF, Taal BG, Nagengast FM , et al. Hereditary nonpolyposis colorectal cancer: results of long-term surveillance in 50 families. Eur J Cancer 1995; 31A (7–8) 1145-1148
    PubMedGoogle Scholar
  • 19 National Comprehensive Cancer Network Genetic/familial high-risk assessment: colorectal (2015); version 1.2015. Available at: http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf . Accessed August 20, 2015
    PubMed
  • 20 Fitzgibbons Jr RJ, Lynch HT, Stanislav GV , et al. Recognition and treatment of patients with hereditary nonpolyposis colon cancer (Lynch syndromes I and II). Ann Surg 1987; 206 (3) 289-295
    CrossrefPubMedGoogle Scholar
  • 21 Wennstrom J, Pierce ER, McKusick VA. Hereditary benign and malignant lesions of the large bowel. Cancer 1974; 34 (3) 850-857
    CrossrefPubMedGoogle Scholar
  • 22 Bisgaard ML, Fenger K, Bülow S, Niebuhr E, Mohr J. Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum Mutat 1994; 3 (2) 121-125
    CrossrefPubMedGoogle Scholar
  • 23 Leoz ML, Carballal S, Moreira L, Ocaña T, Balaguer F. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet 2015; 8: 95-107
    PubMedGoogle Scholar
  • 24 Esplin ED, Snyder MP. Genomic era diagnosis and management of hereditary and sporadic colon cancer. World J Clin Oncol 2014; 5 (5) 1036-1047
    CrossrefPubMedGoogle Scholar
  • 25 Ellis CN. Colonic adenomatous polyposis syndromes: clinical management. Clin Colon Rectal Surg 2008; 21 (4) 256-262
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Fodde R. The APC gene in colorectal cancer. Eur J Cancer 2002; 38 (7) 867-871
    CrossrefPubMedGoogle Scholar
  • 28 Winawer S, Fletcher R, Rex D , et al; Gastrointestinal Consortium Panel. Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 2003; 124 (2) 544-560
    CrossrefPubMedGoogle Scholar
  • 29 Kwong LN, Dove WF. APC and its modifiers in colon cancer. Adv Exp Med Biol 2009; 656: 85-106
    PubMedGoogle Scholar
  • 30 Campos FG, Sulbaran M, Safatle-Ribeiro AV, Martinez CA. Duodenal adenoma surveillance in patients with familial adenomatous polyposis. World J Gastrointest Endosc 2015; 7 (10) 950-959
    PubMedGoogle Scholar
  • 31 Heiskanen I, Kellokumpu I, Järvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis. Endoscopy 1999; 31 (6) 412-416
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Church J. Ileoanal pouch neoplasia in familial adenomatous polyposis: an underestimated threat. Dis Colon Rectum 2005; 48 (9) 1708-1713
    CrossrefPubMedGoogle Scholar
  • 33 Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology 2010; 138 (6) 2044-2058
    CrossrefPubMedGoogle Scholar
  • 34 Sampson JR, Jones N. MUTYH-associated polyposis. Best Pract Res Clin Gastroenterol 2009; 23 (2) 209-218
    CrossrefPubMedGoogle Scholar
  • 35 Ricci MT, Salemme M, Villanacci V, Varesco L. The genetics of inherited predispositions to colorectal polyps: a quick guide for clinicians. Colorectal Dis 2015; 17 (Suppl. 01) 3-9
    PubMedGoogle Scholar
  • 36 Al-Tassan N, Chmiel NH, 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
    CrossrefPubMedGoogle Scholar
  • 37 de Ferro SM, Suspiro A, Fidalgo P , et al. Aggressive phenotype of MYH-associated polyposis with jejunal cancer and intra-abdominal desmoid tumor: report of a case. Dis Colon Rectum 2009; 52 (4) 742-745
    CrossrefPubMedGoogle Scholar
  • 38 Terdiman JP. MYH-associated disease: attenuated adenomatous polyposis of the colon is only part of the story. Gastroenterology 2009; 137 (6) 1883-1886
    CrossrefPubMedGoogle Scholar
  • 39 Boparai KS, Dekker E, Van Eeden S , et al. Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis. Gastroenterology 2008; 135 (6) 2014-2018
    CrossrefPubMedGoogle Scholar
  • 40 Nielsen M, Joerink-van de Beld MC, Jones N , et al. Analysis of MUTYH genotypes and colorectal phenotypes in patients With MUTYH-associated polyposis. Gastroenterology 2009; 136 (2) 471-476
    CrossrefPubMedGoogle Scholar
  • 41 Church JM. Polymerase proofreading-associated polyposis: a new, dominantly inherited syndrome of hereditary colorectal cancer predisposition. Dis Colon Rectum 2014; 57 (3) 396-397
    CrossrefPubMedGoogle Scholar
  • 42 Gallione C, Aylsworth AS, Beis J , et al. Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome. Am J Med Genet A 2010; 152A (2) 333-339
    CrossrefPubMedGoogle Scholar
  • 43 Zhou XP, Woodford-Richens K, Lehtonen R , et al. Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. Am J Hum Genet 2001; 69 (4) 704-711
    CrossrefPubMedGoogle Scholar
  • 44 Calva D, Howe JR. Hamartomatous polyposis syndromes. Surg Clin North Am 2008; 88 (4) 779-817 , vii
    CrossrefPubMedGoogle Scholar
  • 45 Howe JR, Mitros FA, Summers RW. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol 1998; 5 (8) 751-756
    CrossrefPubMedGoogle Scholar
  • 46 McGarrity TJ, Kulin HE, Zaino RJ. Peutz-Jeghers syndrome. Am J Gastroenterol 2000; 95 (3) 596-604
    CrossrefPubMedGoogle Scholar
  • 47 Gruber SB, Entius MM, Petersen GM , et al. Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome. Cancer Res 1998; 58 (23) 5267-5270
    PubMedGoogle Scholar
  • 48 Oncel M, Remzi FH, Church JM, Connor JT, Fazio VW. Benefits of ‘clean sweep’ in Peutz-Jeghers patients. Colorectal Dis 2004; 6 (5) 332-335
    CrossrefPubMedGoogle Scholar
  • 49 Kopácová M, Bures J, Ferko A, Tachecí I, Rejchrt S. Comparison of intraoperative enteroscopy and double-balloon enteroscopy for the diagnosis and treatment of Peutz-Jeghers syndrome. Surg Endosc 2010; 24 (8) 1904-1910
    CrossrefPubMedGoogle Scholar
  • 50 Murday V, Slack J. Inherited disorders associated with colorectal cancer. Cancer Surv 1989; 8 (1) 139-157
    PubMedGoogle Scholar
  • 51 Stambolic V, Suzuki A, de la Pompa JL , et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998; 95 (1) 29-39
    CrossrefPubMedGoogle Scholar
  • 52 Cho YJ, Liang P. Killin is a p53-regulated nuclear inhibitor of DNA synthesis. Proc Natl Acad Sci U S A 2008; 105 (14) 5396-5401
    CrossrefPubMedGoogle Scholar
  • 53 Church J. The ASCRS Textbook of Colon and Rectal Surgery. 2nd ed. Berlin, Germany: Springer Science + Business Media; 2011
    Google Scholar
  • 54 Hawkins NJ, Gorman P, Tomlinson IP, Bullpitt P, Ward RL. Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway. Am J Pathol 2000; 157 (2) 385-392
    CrossrefPubMedGoogle Scholar
  • 55 Lindor NM, Rabe K, Petersen GM , 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
    CrossrefPubMedGoogle Scholar
  • 56 Carethers JM, Stoffel EM. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer. World J Gastroenterol 2015; 21 (31) 9253-9261
    CrossrefPubMedGoogle Scholar
  • 57 Johns LE, Houlston RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol 2001; 96 (10) 2992-3003
    CrossrefPubMedGoogle Scholar
  • 58 Tenesa A, Dunlop MG. New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 2009; 10 (6) 353-358
    PubMedGoogle Scholar
  • 59 National Human Genome Research Institute. Genome-wide association studies (2015). Available at: https://www.genome.gov/20019523 . Accessed August 31, 2015
    PubMedGoogle Scholar
  • 60 Win AK, Macinnis RJ, Hopper JL, Jenkins MA. Risk prediction models for colorectal cancer: a review. Cancer Epidemiol Biomarkers Prev 2012; 21 (3) 398-410
    CrossrefPubMedGoogle Scholar
  • 61 Kalady MF, Church JM. Prophylactic colectomy: Rationale, indications, and approach. J Surg Oncol 2015; 111 (1) 112-117
    CrossrefPubMedGoogle Scholar