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  • Review Article
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Managing hereditary gastrointestinal cancer syndromes: the partnership between genetic counselors and gastroenterologists

Nature Clinical Practice Gastroenterology & Hepatology volume 5, pages 569–582 (2008)Cite this article

A Correction to this article was published on 01 September 2010

Abstract

A standard of care for the recognition and management of patients and families with hereditary gastrointestinal cancer syndromes is emerging, and both gastroenterologists and genetic counselors have an important role. This Review considers these roles and outlines the partnership needed between gastroenterologists and genetic counselors. The role of the gastroenterologist involves careful sampling of polyps and tumors, and requires a basic working knowledge of the features of hereditary gastrointestinal cancer syndromes. The role of the genetic counselor is to gather and synthesize family history and pathology information, formulate a genetic differential diagnosis, determine a genetic testing strategy, guide medical management and help patients communicate information to their relatives. Managing the complex logistics of testing the best candidate in the family, facilitating informed consent, outlining costs to patients and interpreting test results are also responsibilities assumed by genetic counselors. In addition, genetic counselors help physicians meet their ethical and medicolegal obligations with respect to patient management and family communication. Referral schemata for patients with polyposis and nonpolyposis features are presented in this Review, along with comprehensive tables that outline the features of well-known and rare syndromes that heighten the risk of gastrointestinal malignancy.

Key Points

  • Gastroenterologists can assist in the genetic workup through careful sampling of polyps and tumors and having a basic working knowledge of hereditary gastrointestinal cancer syndromes

  • An urgent genetic consultation can be requested at the time of cancer diagnosis, which can help clarify the need for prophylactic colorectal, endometrial or ovarian surgery and aid in patient decision making

  • Genetic counselors gather and synthesize detailed information on polyps, tumors and family history to devise a genetic testing strategy according to established algorithms, which might entail testing of relatives' tumor tissue and blood

  • Genetic counselors help physicians meet their ethical and medicolegal obligations with respect to patient management and family communication

  • The Genetic Information Nondiscrimination Act passed in May 2008 will bolster existing US federal and state protection against the inappropriate use of genetic information by health insurers and employers

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Figure 1: Referral schema used for patients with gastrointestinal cancers at the Evanston Northwestern Healthcare Center for Medical Genetics, Evanston, IL.
Figure 2: Referral schema used for patients with gastrointestinal polyps found on endoscopy at the Evanston Northwestern Healthcare Center for Medical Genetics, Evanston, IL.

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References

  1. Lynch PM (2007) New issues in genetic counseling of hereditary colon cancer. Clin Cancer Res 13: 6857s–6861s

    Article  PubMed  Google Scholar 

  2. Grover S et al. (2004) Physician assessment of family cancer history and referral for genetic evaluation in colorectal cancer patients. Clin Gastroenterol Hepatol 2: 813–819

    Article  PubMed  Google Scholar 

  3. Petersen GM et al. (1999) Genetic testing and counseling for hereditary forms of colorectal cancer. Cancer 86: 2540–2550

    Article  CAS  PubMed  Google Scholar 

  4. Hampel H et al. (2000) Hereditary colorectal cancer: risk assessment and management. Clin Genet 58: 89–97

    Article  CAS  PubMed  Google Scholar 

  5. American Gastroenterological Association (2001) American Gastroenterological Association medical position statement: hereditary colorectal cancer and genetic testing. Gastroenterology 121: 195–197

  6. Standard Task Force; American Society of Colon and Rectal Surgeons; Collaborative Group of the Americas on Inherited Colorectal Cancer (2001) Practice parameters for the identification and testing of patients at risk for dominantly inherited colorectal cancer. Dis Colon Rectum 44: 1403

  7. American Society of Clinical Oncology (2003) American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol 21: 2397–2406

  8. Lynch HT et al. (2007) Who should be sent for genetic testing in hereditary colorectal cancer syndromes. J Clin Oncol 25: 3534–3542

    Article  PubMed  Google Scholar 

  9. National Comprehensive Cancer Network (v.2 online 17 June 2008) NCCN clinical practice guidelines in oncology: colorectal cancer screening [http://www.nccn.org/professionals/physician_gls/PDF/colorectal_screening.pdf] (v.1 accessed 20 April 2008)

  10. Giardiello FM et al. (2001) AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 121: 198–213

    Article  CAS  PubMed  Google Scholar 

  11. Neklason DW et al. (2008) American founder mutation for attenuated familial adenomatous polyposis. Clin Gastroenterol Hepatol 6: 46–52

    Article  CAS  PubMed  Google Scholar 

  12. Trepanier A et al. (2004) Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors. J Genet Couns 13: 83–114

    Article  PubMed  Google Scholar 

  13. Schreibman IR et al. (2005) The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol 100: 476–490

    Article  PubMed  Google Scholar 

  14. Jass JR et al. (1988) Juvenile polyposis—a precancerous condition. Histopathology 13: 619–630

    Article  CAS  PubMed  Google Scholar 

  15. Knudsen AL et al. (2003) Attenuated familial adenomatous polyposis (AFAP): a review of the literature. Fam Cancer 2: 43–55

    Article  PubMed  Google Scholar 

  16. Burt RW and Jass JR (2000) Hyperplastic Polyposis. In World Health Organization classification of tumours. Pathology & genetics. Tumours of the digestive system (Eds Hamilton SR et al.) Lyon, France: IARC Press

    Google Scholar 

  17. Umar A et al. (2004) Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96: 261–268

    Article  CAS  PubMed  Google Scholar 

  18. Vasen HF et al. (1991) The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34: 424–425

    Article  CAS  PubMed  Google Scholar 

  19. Vasen HF et al. (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116: 1453–1456

    Article  CAS  PubMed  Google Scholar 

  20. Vasen HF et al. (2005) Progress in genetic testing, classification, and identification of Lynch syndrome. JAMA 293: 2028–2030

    Article  CAS  PubMed  Google Scholar 

  21. Choi MY et al. (2007) Microsatellite instability is frequently observed in rectal cancer and influenced by neoadjuvant chemoradiation. Int J Radiat Oncol Biol Phys 68: 1584

    Article  PubMed  Google Scholar 

  22. Balaguer F et al. (2008) Validation and extension of the PREMM1,2 model in a population-based cohort of colorectal cancer patients. Gastroenterology 134: 39–46

    Article  PubMed  Google Scholar 

  23. Kuismanen SA et al. (2002) Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability. Am J Pathol 160: 1953–1958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Berends MJ et al. (2001) MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non-hereditary endometrial hyperplasia and cancer. Int J Cancer 92: 398–403

    Article  CAS  PubMed  Google Scholar 

  25. Whelan AJ et al. (2002) MSI in endometrial carcinoma: absence of MLH1 promoter methylation is associated with increased familial risk for cancers. Int J Cancer 99: 697–704

    Article  CAS  PubMed  Google Scholar 

  26. Goodfellow PJ et al. (2003) Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proc Natl Acad Sci USA 100: 5908–5913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ponti G et al. (2005) Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry. Cancer 103: 1018–1025

    Article  PubMed  Google Scholar 

  28. Guillem JG et al. (2006) ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. J Clin Oncol 24: 4642–4660

    Article  PubMed  Google Scholar 

  29. de Vos tot Nederveen Cappel WH et al. (2003) Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect. Gut 52: 1752–1755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Syngal S et al. (1998) Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations. Ann Intern Med 129: 787–796

    Article  CAS  PubMed  Google Scholar 

  31. Schmeler KM et al. (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354: 261–269

    Article  CAS  PubMed  Google Scholar 

  32. Chen LM et al. (2007) Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families. Obstet Gynecol 110: 18–25

    Article  PubMed  Google Scholar 

  33. American Society of Human Genetics (1975) Genetic counseling. Am J Hum Genet 27: 240–242

  34. National Society of Genetic Counselors [http://www.nsgc.org]

  35. National Cancer Institute Genetic Services Directory [http://cancer.gov/search/genetics_services]

  36. Bennett RL (1999) The Practical Guide to the Genetic Family History. New York: Wiley-Liss

    Book  Google Scholar 

  37. Bandipalliam P (2005) Syndrome of early onset colon cancers, hematologic malignancies and features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer 4: 323–333

    Article  CAS  PubMed  Google Scholar 

  38. Murff HJ et al. (2004) Does this patient have a family history of cancer? An evidence-based analysis of the accuracy of family cancer history. JAMA 292: 1480–1489

    Article  CAS  PubMed  Google Scholar 

  39. Lynch HT et al. (2004) Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC-like families: problems in diagnosis, surveillance, and management. Cancer 100: 53–64

    Article  PubMed  Google Scholar 

  40. Hampel H et al. (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352: 1851–1860

    Article  CAS  PubMed  Google Scholar 

  41. Hampel H et al. (2006) Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 66: 7810–7817

    Article  CAS  PubMed  Google Scholar 

  42. Lynch HT et al. (2005) Molecular screening for the Lynch syndrome—better than family history. N Engl J Med 352: 1920–1922

    Article  CAS  PubMed  Google Scholar 

  43. Madlensky L et al. (2007) Accuracy of colorectal polyp self-reports: findings from the colon cancer family registry. Cancer Epidemiol Biomarkers Prev 16: 1898–1901

    Article  PubMed  Google Scholar 

  44. Watson P et al. (2003) Carrier risk status changes resulting from mutation testing in hereditary non-polyposis colorectal cancer and hereditary breast-ovarian cancer. J Med Genet 40: 591–596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lynch HT et al. (2004) A founder mutation of the MSH2 gene and hereditary nonpolyposis colorectal cancer in the United States. JAMA 291: 718–724

    Article  CAS  PubMed  Google Scholar 

  46. Wagner A et al. (2003) Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Am J Hum Genet 72: 1088–1100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Peltomaki P (2001) Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum Mol Genet 10: 735–740

    Article  CAS  PubMed  Google Scholar 

  48. Goldgar DE et al. (2004) Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet 75: 535–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Weber B (1996) Breast cancer susceptibility genes: current challenges and future promises. Ann Intern Med 124: 1088–1090

    Article  CAS  PubMed  Google Scholar 

  50. Ramsey SD et al. (2001) Cost-effectiveness of microsatellite instability screening as a method for detecting hereditary nonpolyposis colorectal cancer. Ann Intern Med 135: 577–588

    Article  CAS  PubMed  Google Scholar 

  51. Offit K et al. (2004) The “duty to warn” a patient's family members about hereditary disease risks. JAMA 292: 1469–1473

    Article  CAS  PubMed  Google Scholar 

  52. GovTrack.us (online April 2007) HR 493: Genetic Information Nondiscrimination Act of 2008 [http://www.govtrack.us/congress/bill.xpd?bill=h110-493]

  53. Hudson KL et al. (2008) Keeping pace with the times—the Genetic Information Nondiscrimination Act of 2008. N Engl J Med 358: 2661–2663

    Article  CAS  PubMed  Google Scholar 

  54. Greely HT (2005) Banning genetic discrimination. N Engl J Med 353: 865–867

    Article  CAS  PubMed  Google Scholar 

  55. Lindor NM et al. (2006) Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 296: 1507–1517

    Article  CAS  PubMed  Google Scholar 

  56. Lynch PM (2008) Standards of care in diagnosis and testing for hereditary colon cancer. Fam Cancer 7: 65–72

    Article  PubMed  Google Scholar 

  57. Lindor NM et al. (1998) The concise handbook of family cancer syndromes: Mayo Familial Cancer Program. J Natl Cancer Inst 90: 1039–1071

    Article  CAS  PubMed  Google Scholar 

  58. Garber JE et al. (2005) Hereditary cancer predisposition syndromes. J Clin Oncol 23: 276–292

    Article  PubMed  Google Scholar 

  59. Schneider K (2002) Counseling About Cancer: Strategies for Genetic Counseling, edn 2. New York: Wiley-Liss

    Google Scholar 

  60. Online Mendelian Inheritance in Man [http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim]

  61. Lindor NM et al. (2005) Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA 293: 1979–1985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Caldas C et al. (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36: 873–880

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Oliveira C et al. (2006) Genetics, pathology, and clinics of familial gastric cancer. Int J Surg Pathol 14: 21–33

    Article  CAS  PubMed  Google Scholar 

  64. Huntsman DG et al. (2001) Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations. N Engl J Med 344: 1904–1909

    Article  CAS  PubMed  Google Scholar 

  65. South CD et al. (2008) The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst 100: 277–281

    Article  CAS  PubMed  Google Scholar 

  66. Gene Tests Website [http://www.genetests.org/]

  67. Seruca R et al. (1991) Familial gastric polyposis revisited: autosomal dominant inheritance confirmed. Cancer Genet Cytogenet 53: 97–100

    Article  CAS  PubMed  Google Scholar 

  68. Carneiro F et al. (1993) Hyperplastic polyposis and diffuse carcinoma of the stomach: a study of a family. Cancer 72: 323–329

    Article  CAS  PubMed  Google Scholar 

  69. Tomlinson I et al. (1999) Inherited susceptibility to colorectal adenomas and carcinomas: evidence for a new predisposition gene on 15q14-q22. Gastroenterology 116: 789–795

    Article  CAS  PubMed  Google Scholar 

  70. Jaeger EE et al. (2003) An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome. Am J Hum Genet 72: 1261–1267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Cao X et al. (2006) Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function. J Med Genet 43: e13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rashid A et al. (2000) Phenotypic and molecular characteristics of hyperplastic polyposis. Gastroenterology 119: 323–332

    Article  CAS  PubMed  Google Scholar 

  73. Ferrandez A et al. (2004) Phenotypic characteristics and risk of cancer development in hyperplastic polyposis: case series and literature review. Am J Gastroenterol 99: 2012–2018

    Article  PubMed  Google Scholar 

  74. Gallione CJ et al. (2004) A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet 363: 852–859

    Article  CAS  PubMed  Google Scholar 

  75. Lipton L et al. (2004) The multiple colorectal adenoma phenotype and MYH, a base excision repair gene. Clin Gastroenterol Hepatol 2: 633–638

    Article  CAS  PubMed  Google Scholar 

  76. Lipton L et al. (2006) The genetics of FAP and FAP-like syndromes. Fam Cancer 5: 221–226

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Charles P Vega, University of California, Irvine, CA, USA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. WS Rubinstein is Medical Director and SM Weissman is a Licensed and Certified Genetic Counselor at the Evanston Northwestern Healthcare Center for Medical Genetics, Evanston, IL, USA.,

    Wendy S Rubinstein & Scott M Weissman

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  1. Wendy S Rubinstein
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Correspondence to Wendy S Rubinstein.

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Supplementary Table 1

Other hereditary cancer syndromes with some gastrointestinal involvement.60 (DOC 51 kb)

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Rubinstein, W., Weissman, S. Managing hereditary gastrointestinal cancer syndromes: the partnership between genetic counselors and gastroenterologists. Nat Rev Gastroenterol Hepatol 5, 569–582 (2008). https://doi.org/10.1038/ncpgasthep1235

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