NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019

Featured Updates to the NCCN Guidelines

Restricted access

Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.

  • 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34.

  • 2.

    Jasperson KW, Tuohy TM, Neklason DW, . Hereditary and familial colon cancer. Gastroenterology 2010;138:2044–2058.

  • 3.

    Lichtenstein P, Holm NV, Verkasalo PK, . Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000;343:78–85.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Rustgi AK. The genetics of hereditary colon cancer. Genes Dev 2007;21:2525–2538.

  • 5.

    Taylor DP, Burt RW, Williams MS, . Population-based family history-specific risks for colorectal cancer: a constellation approach. Gastroenterology 2010;138:877–885.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Committee opinion no. 634: hereditary cancer syndromes and risk assessment. Obstet Gynecol 2015;125:1538–1543.

  • 7.

    Ballester V, Cruz-Correa M. How and when to consider genetic testing for colon cancer? Gastroenterology 2018;155:955–959.

  • 8.

    Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003;348:919–932.

  • 9.

    Samadder NJ, Baffy N, Giridhar KV, . Hereditary cancer syndromes—a primer on diagnosis and management, part 2: gastrointestinal cancer syndromes. Mayo Clin Proc 2019;94:1099–1116.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Shaco-Levy R, Jasperson KW, Martin K, . Gastrointestinal polyposis in Cowden syndrome. J Clin Gastroenterol 2017;51:e60–e67.

  • 11.

    Boursi B, Sella T, Liberman E, . The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews. Eur J Cancer 2013;49:3680–3685.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Locker GY, Kaul K, Weinberg DS, . The I1307K APC polymorphism in Ashkenazi Jews with colorectal cancer: clinical and pathologic features. Cancer Genet Cytogenet 2006;169:33–38.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Bellido F, Pineda M, Aiza G, . POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genet Med 2016;18:325–332.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Esteban-Jurado C, Giménez-Zaragoza D, Muñoz J, . POLE and POLD1 screening in 155 patients with multiple polyps and early-onset colorectal cancer. Oncotarget 2017;8:26732–26743.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Carballal S, Rodríguez-Alcalde D, Moreira L, . Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study. Gut 2016;65:1829–1837.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Gupta S, Provenzale D, Regenbogen SE, . NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017. J Natl Compr Canc Netw 2017;15:1465–1475.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Yurgelun MB, Allen B, Kaldate RR, . Identification of a variety of mutations in cancer predisposition genes in patients with suspected Lynch syndrome. Gastroenterology 2015;149:604–613.e20.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Aaltonen LA, Salovaara R, Kristo P, . Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 1998;338:1481–1487.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Hampel H, Frankel WL, Martin E, . Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005;352:1851–1860.

  • 20.

    Hampel H, Frankel WL, Martin E, . Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol 2008;26:5783–5788.

  • 21.

    Buchanan DD, Rosty C, Clendenning M, . Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome). Appl Clin Genet 2014;7:183–193.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Hampel H, Frankel W, Panescu J, . Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 2006;66:7810–7817.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010;138:2073–2087.e3.

  • 24.

    Kempers MJ, Kuiper RP, Ockeloen CW, . Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol 2011;12:49–55.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Rumilla K, Schowalter KV, Lindor NM, . Frequency of deletions of EPCAM (TACSTD1) in MSH2-associated Lynch syndrome cases. J Mol Diagn 2011;13:93–99.

  • 26.

    Baglietto L, Lindor NM, Dowty JG, . Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 2010;102:193–201.

  • 27.

    Engel C, Loeffler M, Steinke V, . Risks of less common cancers in proven mutation carriers with lynch syndrome. J Clin Oncol 2012;30:4409–4415.

  • 28.

    Møller P, Seppälä TT, Bernstein I, . Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut 2018;67:1306–1316.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Ryan S, Jenkins MA, Win AK. Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2014;23:437–449.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Vasen HF, Watson P, Mecklin JP, . New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 1999;116:1453–1456.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Umar A, Boland CR, Terdiman JP, . Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004;96:261–268.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Barnetson RA, Tenesa A, Farrington SM, . Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med 2006;354:2751–2763.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Rodriguez-Bigas MA, Boland CR, Hamilton SR, . A National Cancer Institute workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 1997;89:1758–1762.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Raedle J, Trojan J, Brieger A, . Bethesda guidelines: relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer. Ann Intern Med 2001;135:566–576.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Piñol V, Castells A, Andreu M, . Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA 2005;293:1986–1994.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Vasen HF, Mecklin JP, Khan PM, . The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991;34:424–425.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Green RC, Parfrey PS, Woods MO, . Prediction of Lynch syndrome in consecutive patients with colorectal cancer. J Natl Cancer Inst 2009;101:331–340.

  • 38.

    Sjursen W, Haukanes BI, Grindedal EM, . Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers. J Med Genet 2010;47:579–585.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Moreira L, Balaguer F, Lindor N, . Identification of Lynch syndrome among patients with colorectal cancer. JAMA 2012;308:1555–1565.

  • 40.

    Mvundura M, Grosse SD, Hampel H, . The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genet Med 2010;12:93–104.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Pérez-Carbonell L, Ruiz-Ponte C, Guarinos C, . Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer. Gut 2012;61:865–872.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Adar T, Rodgers LH, Shannon KM, . Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome. Cancer 2018;124:3145–3153.

  • 43.

    Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med 2009;11:35–41.

    • Search Google Scholar
    • Export Citation
  • 44.

    Ladabaum U, Wang G, Terdiman J, . Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med 2011;155:69–79.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Palomaki GE, McClain MR, Melillo S, . EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med 2009;11:42–65.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Balmaña J, Balaguer F, Cervantes A, . Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol 2013;24(Suppl 6):vi73–80.

  • 47.

    Giardiello FM, Allen JI, Axilbund JE, . Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2014;147:502–526.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Stoffel EM, Mangu PB, Gruber SB, . Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol 2015;33:209–217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49.

    Marquez E, Geng Z, Pass S, . Implementation of routine screening for Lynch syndrome in university and safety-net health system settings: successes and challenges. Genet Med 2013;15:925–932.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Balmaña J, Stockwell DH, Steyerberg EW, . Prediction of MLH1 and MSH2 mutations in Lynch syndrome. JAMA 2006;296:1469–1478.

  • 51.

    Chen S, Wang W, Lee S, . Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA 2006;296:1479–1487.

  • 52.

    Kastrinos F, Steyerberg EW, Mercado R, . The PREMM(1,2,6) model predicts risk of MLH1, MSH2, and MSH6 germline mutations based on cancer history. Gastroenterology 2011;140:73–81.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Goverde A, Spaander MCW, Nieboer D, . Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers. Fam Cancer 2018;17:361–370.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    Kastrinos F, Uno H, Ukaegbu C, . Development and validation of the PREMM5 model for comprehensive risk assessment of Lynch syndrome. J Clin Oncol 2017;35:2165–2172.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Idos G, Gupta S. When should patients undergo genetic testing for hereditary colon cancer syndromes? Clin Gastroenterol Hepatol 2018;16:181–183.

  • 56.

    Beamer LC, Grant ML, Espenschied CR, . Reflex immunohistochemistry and microsatellite instability testing of colorectal tumors for Lynch syndrome among US cancer programs and follow-up of abnormal results. J Clin Oncol 2012;30:1058–1063.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    Cragun D, DeBate RD, Vadaparampil ST, . Comparing universal Lynch syndrome tumor-screening programs to evaluate associations between implementation strategies and patient follow-through. Genet Med 2014;16:773–782.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58.

    Shaikh T, Handorf EA, Meyer JE, . Mismatch repair deficiency testing in patients with colorectal cancer and nonadherence to testing guidelines in young adults. JAMA Oncol 2018;4:e173580.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59.

    Pearlman R, Frankel WL, Swanson B, . Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol 2017;3:464–471.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60.

    Yurgelun MB, Kulke MH, Fuchs CS, . Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol 2017;35:1086–1095.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 2198 2198 271
PDF Downloads 816 816 67
EPUB Downloads 0 0 0