Lynch Syndrome

Chapter

Abstract

Lynch syndrome is a highly penetrant hereditary cancer syndrome caused by pathogenic germline variants in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2, and EPCAM. Historically identified on the basis of family history of colorectal and endometrial cancers exhibiting autosomal dominant inheritance, universal screening of CRCs and endometrial cancers for features of MMR deficiency, together with cascade genetic testing in families, is at present the most effective approach for identifying individuals with Lynch syndrome. Here we review the history of Lynch syndrome, as well as the clinical and molecular investigations that have contributed to our understanding of Lynch syndrome and informed current approaches to diagnosis and clinical management.

Keywords

Lynch syndrome Genetic Mismatch repair 

References

  1. 1.
    Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Speizer FE, Willett WC. A prospective study of family history and the risk of colorectal cancer. N Engl J Med. 1994;331(25):1669–74.  https://doi.org/10.1056/NEJM199412223312501.CrossRefPubMedGoogle Scholar
  2. 2.
    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):1453–6.CrossRefGoogle Scholar
  3. 3.
    Evaluation of Genomic Applications in P, Prevention Working G. 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(1):35–41.  https://doi.org/10.1097/GIM.0b013e31818fa2ff.CrossRefGoogle Scholar
  4. 4.
    Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, et al. 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(2):502–26.  https://doi.org/10.1053/j.gastro.2014.04.001.CrossRefPubMedGoogle Scholar
  5. 5.
    Boland CR, Lynch HT. The history of Lynch syndrome. Familial Cancer. 2013;12(2):145–57.  https://doi.org/10.1007/s10689-013-9637-8.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Warthin AS. The further study of a cancer family. J Cancer Research. 1925;9:279–86.Google Scholar
  7. 7.
    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):424–5.CrossRefGoogle Scholar
  8. 8.
    Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260(5109):816–9.CrossRefGoogle Scholar
  9. 9.
    Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reval a new mechanism for colonic carcinogenesis. Nature. 1993;363(6429):558–561.CrossRefGoogle Scholar
  10. 10.
    Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1994;77(1):1. p following 166.CrossRefGoogle Scholar
  11. 11.
    Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993;75(6):1215–25.CrossRefGoogle Scholar
  12. 12.
    Peltomaki P, Aaltonen LA, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, et al. Genetic mapping of a locus predisposing to human colorectal cancer. Science. 1993;260(5109):810–2.CrossRefGoogle Scholar
  13. 13.
    Lindblom A, Tannergard P, Werelius B, Nordenskjold M. Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. Nat Genet. 1993;5(3):279–82.  https://doi.org/10.1038/ng1193-279.CrossRefPubMedGoogle Scholar
  14. 14.
    Bronner CE, Baker SM, Morrison PT et al. Mutation in the DNA Mismatch Repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994;368(6468): 258–261.CrossRefGoogle Scholar
  15. 15.
    Papadopoulos N, Nicolaides NC, Wei YF et al. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994;263(5153):1625–29.CrossRefGoogle Scholar
  16. 16.
    Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994;371(6492):75–80.  https://doi.org/10.1038/371075a0.CrossRefPubMedGoogle Scholar
  17. 17.
    Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet. 1997;17(3):271–2.  https://doi.org/10.1038/ng1197-271.CrossRefPubMedGoogle Scholar
  18. 18.
    Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3′ exons of TACSTD1. Nat Genet. 2009;41(1):112–7.  https://doi.org/10.1038/ng.283.CrossRefPubMedGoogle Scholar
  19. 19.
    Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, 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(22):5248–57.PubMedGoogle Scholar
  20. 20.
    Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005;352(18):1851–60.CrossRefGoogle Scholar
  21. 21.
    Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol. 2017;35(10):1086–95.  https://doi.org/10.1200/JCO.2016.71.0012.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Goodenberger ML, Thomas BC, Riegert-Johnson D, Boland CR, Plon SE, Clendenning M, et al. PMS2 monoallelic mutation carriers: the known unknown. Genet Med. 2016;18(1):13–9.  https://doi.org/10.1038/gim.2015.27.CrossRefPubMedGoogle Scholar
  23. 23.
    Haraldsdottir S, Rafnar T, Frankel WL, Einarsdottir S, Sigurdsson A, Hampel H, et al. Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2. Nat Commun. 2017;8:14755.  https://doi.org/10.1038/ncomms14755.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, et al. Prevalence and penetrance of major genes and polygenes for colorectal cancer. Cancer Epidemiol Biomark Prev. 2017;26(3):404–12.  https://doi.org/10.1158/1055-9965.EPI-16-0693.CrossRefGoogle Scholar
  25. 25.
    Pinheiro M, Pinto C, Peixoto A, Veiga I, Lopes P, Henrique R, et al. Target gene mutational pattern in Lynch syndrome colorectal carcinomas according to tumour location and germline mutation. Br J Cancer. 2015;113(4):686–92.  https://doi.org/10.1038/bjc.2015.281.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Quehenberger F, Vasen HF, van Houwelingen HC. Risk of colorectal and endometrial cancer for carriers of mutations of the hMLH1 and hMSH2 gene: correction for ascertainment. J Med Genet. 2005;42(6):491–6. 42/6/491 [pii].  https://doi.org/10.1136/jmg.2004.024299.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Jenkins MA, Baglietto L, Dowty JG, Van Vliet CM, Smith L, Mead LJ, et al. Cancer risks for mismatch repair gene mutation carriers: a population-based early onset case-family study. Clin Gastroenterol Hepatol. 2006;4(4):489–98.  https://doi.org/10.1016/j.cgh.2006.01.002. S1542-3565(06)00049-8 [pii].CrossRefPubMedGoogle Scholar
  28. 28.
    Stoffel E, Mukherjee B, Raymond VM, Tayob N, Kastrinos F, Sparr J, et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology. 2009;137(5):1621–7.  https://doi.org/10.1053/j.gastro.2009.07.039. S0016-5085(09)01158-5 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81(2):214–8.CrossRefGoogle Scholar
  30. 30.
    Moller P, Seppala TT, Bernstein I, Holinski-Feder E, Sala P, Gareth Evans D, et al. 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. 2017.  https://doi.org/10.1136/gutjnl-2017-314057.
  31. 31.
    Win AK, Lindor NM, Winship I, Tucker KM, Buchanan DD, Young JP, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013;105(4):274–9.  https://doi.org/10.1093/jnci/djs525.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Vasen HF, Blanco I, Aktan-Collan K, Gopie JP, Alonso A, Aretz S, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013;62(6):812–23.  https://doi.org/10.1136/gutjnl-2012-304356.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008;135(2):419–28.  https://doi.org/10.1053/j.gastro.2008.04.026. S0016-5085(08)00737-3 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Baglietto L, Lindor NM, Dowty JG, White DM, Wagner A, Gomez Garcia EB, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010;102(3):193–201.  https://doi.org/10.1093/jnci/djp473. djp473 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Vasen HF, Stormorken A, Menko FH, Nagengast FM, Kleibeuker JH, Griffioen G, et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol. 2001;19(20):4074–80.CrossRefGoogle Scholar
  36. 36.
    Engel C, Loeffler M, Steinke V, Rahner N, Holinski-Feder E, Dietmaier W, et al. Risks of less common cancers in proven mutation carriers with Lynch syndrome. J Clin Oncol. 2012;30(35):4409–15.  https://doi.org/10.1200/JCO.2012.43.2278.CrossRefPubMedGoogle Scholar
  37. 37.
    Capelle LG, Van Grieken NC, Lingsma HF, Steyerberg EW, Klokman WJ, Bruno MJ, et al. Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands. Gastroenterology. 2010;138(2):487–92.  https://doi.org/10.1053/j.gastro.2009.10.051. S0016-5085(09)01948-9 [pii].CrossRefPubMedGoogle Scholar
  38. 38.
    van der Post RS, Kiemeney LA, Ligtenberg MJ, Witjes JA, Hulsbergen-van de Kaa CA, Bodmer D, et al. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet. 2010;47(7):464–70.  https://doi.org/10.1136/jmg.2010.076992.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009;302(16):1790–5.  https://doi.org/10.1001/jama.2009.1529. 302/16/1790 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Win AK, Young JP, Lindor NM, Tucker KM, Ahnen DJ, Young GP, et al. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol. 2012;30(9):958–64.  https://doi.org/10.1200/JCO.2011.39.5590.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Raymond VM, Mukherjee B, Wang F, Huang SC, Stoffel EM, Kastrinos F, et al. Elevated risk of prostate cancer among men with Lynch syndrome. J Clin Oncol. 2013;31(14):1713–8.  https://doi.org/10.1200/JCO.2012.44.1238.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kempers MJ, Kuiper RP, Ockeloen CW, Chappuis PO, Hutter P, Rahner N, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol. 2011;12(1):49–55.  https://doi.org/10.1016/S1470-2045(10)70265-5. S1470-2045(10)70265-5 [pii].CrossRefPubMedGoogle Scholar
  43. 43.
    Goodenberger ML, Thomas BC, Riegert-Johnson D, Boland CR, Plon SE, Clendenning M, et al. PMS2 monoallelic mutation carriers: the known unknown. Genet Med. 2015.  https://doi.org/10.1038/gim.2015.27.
  44. 44.
    Moller P, Seppala T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017;66(3):464–72.  https://doi.org/10.1136/gutjnl-2015-309675.CrossRefPubMedGoogle Scholar
  45. 45.
    Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223–62.; quiz 63.  https://doi.org/10.1038/ajg.2014.435.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342(2):69–77.  https://doi.org/10.1056/NEJM200001133420201.CrossRefGoogle Scholar
  47. 47.
    Carethers JM, Smith EJ, Behling CA, Nguyen L, Tajima A, Doctolero RT, et al. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology. 2004;126(2):394–401.CrossRefGoogle Scholar
  48. 48.
    Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, 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):247–57.  https://doi.org/10.1056/NEJMoa022289.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.  https://doi.org/10.1056/NEJMoa1500596.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13.  https://doi.org/10.1126/science.aan6733.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, et al. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut. 2011;60(7):950–7.  https://doi.org/10.1136/gut.2010.228056.CrossRefPubMedGoogle Scholar
  52. 52.
    Win AK, Parry S, Parry B, Kalady MF, Macrae FA, Ahnen DJ, et al. Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers. Ann Surg Oncol. 2013;20(6):1829–36.  https://doi.org/10.1245/s10434-012-2858-5.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Vasen HF, Abdirahman M, Brohet R, Langers AM, Kleibeuker JH, van Kouwen M, et al. One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Gastroenterology. 2010;138(7):2300–6.  https://doi.org/10.1053/j.gastro.2010.02.053. S0016-5085(10)00326-4 [pii].CrossRefPubMedGoogle Scholar
  54. 54.
    Jarvinen HJ, Renkonen-Sinisalo L, Aktan-Collan K, Peltomaki P, Aaltonen LA, Mecklin JP. Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol. 2009;27(28):4793–7.  https://doi.org/10.1200/JCO.2009.23.7784.CrossRefPubMedGoogle Scholar
  55. 55.
    Engel C, Rahner N, Schulmann K, Holinski-Feder E, Goecke TO, Schackert HK, et al. Efficacy of annual colonoscopic surveillance in individuals with hereditary nonpolyposis colorectal cancer. Clin Gastroenterol Hepatol. 2010;8(2):174–82.  https://doi.org/10.1016/j.cgh.2009.10.003.CrossRefPubMedGoogle Scholar
  56. 56.
    Edelstein DL, Axilbund J, Baxter M, Hylind LM, Romans K, Griffin CA, et al. Rapid development of colorectal neoplasia in patients with Lynch syndrome. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2011;9(4):340–3.  https://doi.org/10.1016/j.cgh.2010.10.033.CrossRefGoogle Scholar
  57. 57.
    Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348(10):919–32.  https://doi.org/10.1056/NEJMra012242. 348/10/919 [pii].CrossRefPubMedGoogle Scholar
  58. 58.
    Ahadova A, von Knebel Doeberitz M, Blaker H, Kloor M. CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome. Familial Cancer. 2016;15(4):579–86.  https://doi.org/10.1007/s10689-016-9899-z.CrossRefPubMedGoogle Scholar
  59. 59.
    Kaminski MF, Hassan C, Bisschops R, Pohl J, Pellise M, Dekker E, et al. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2014;46(5):435–49.  https://doi.org/10.1055/s-0034-1365348.CrossRefPubMedGoogle Scholar
  60. 60.
    Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378(9809):2081–7.  https://doi.org/10.1016/S0140-6736(11)61049-0.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Goverde A, Spaander MC, van Doorn HC, Dubbink HJ, van den Ouweland AM, Tops CM, et al. Cost-effectiveness of routine screening for Lynch syndrome in endometrial cancer patients up to 70years of age. Gynecol Oncol. 2016;143(3):453–9.  https://doi.org/10.1016/j.ygyno.2016.10.008.CrossRefPubMedGoogle Scholar
  62. 62.
    Committee on Practice B-G, Society of Gynecologic O. ACOG Practice Bulletin No. 147: Lynch syndrome. Obstet Gynecol. 2014;124(5):1042–54.  https://doi.org/10.1097/01.AOG.0000456325.50739.72.CrossRefGoogle Scholar
  63. 63.
    Bonadona V, Bonaiti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305(22):2304–10.  https://doi.org/10.1001/jama.2011.743.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Schmeler KM, Lynch HT, Chen LM, Munsell MF, Soliman PT, Clark MB, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006;354(3):261–9.  https://doi.org/10.1056/NEJMoa052627.CrossRefPubMedGoogle Scholar
  65. 65.
    Win AK, Lindor NM, Young JP, Macrae FA, Young GP, Williamson E, et al. Risks of primary extracolonic cancers following colorectal cancer in Lynch syndrome. J Natl Cancer Inst. 2012;104(18):1363–72.  https://doi.org/10.1093/jnci/djs351.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Watson P, Vasen HF, Mecklin JP, Bernstein I, Aarnio M, Jarvinen HJ, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer. 2008;123(2):444–9.  https://doi.org/10.1002/ijc.23508.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Kastrinos F, Stoffel EM, Balmana J, Steyerberg EW, Mercado R, Syngal S. Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States. Cancer Epidemiol Biomark Prev. 2008;17(8):2044–51.  https://doi.org/10.1158/1055-9965.EPI-08-0301. 17/8/2044 [pii].CrossRefGoogle Scholar
  68. 68.
    Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62(3):339–47.  https://doi.org/10.1136/gutjnl-2012-303108.CrossRefPubMedGoogle Scholar
  69. 69.
    Rodriguez-Bigas MA, Boland CR, Hamilton SR, Henson DE, Jass JR, Khan PM, et al. A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst. 1997;89(23):1758–62.CrossRefGoogle Scholar
  70. 70.
    Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261–8.CrossRefGoogle Scholar
  71. 71.
    Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, et al. Identification of Lynch syndrome among patients with colorectal cancer. JAMA. 2012;308(15):1555–65.  https://doi.org/10.1001/jama.2012.13088. 1383232 [pii].CrossRefPubMedGoogle Scholar
  72. 72.
    Palomaki GE, McClain MR, Melillo S, Hampel HL, Thibodeau SN. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med. 2009;11(1):42–65.  https://doi.org/10.1097/GIM.0b013e31818fa2db.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, et al. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008;26(35):5783–8.  https://doi.org/10.1200/JCO.2008.17.5950. JCO.2008.17.5950 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Mensenkamp AR, Vogelaar IP, van Zelst-Stams WA, Goossens M, Ouchene H, Hendriks-Cornelissen SJ, et al. Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology. 2014;146(3):643–6 e8.  https://doi.org/10.1053/j.gastro.2013.12.002.CrossRefPubMedGoogle Scholar
  75. 75.
    Haraldsdottir S, Hampel H, Tomsic J, Frankel WL, Pearlman R, de la Chapelle A, et al. Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology. 2014;147(6):1308–16 e1.  https://doi.org/10.1053/j.gastro.2014.08.041.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Ladabaum U, Wang G, Terdiman J, Blanco A, Kuppermann M, Boland CR, et al. Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med. 2011;155(2):69–79.  https://doi.org/10.1059/0003-4819-155-2-201107190-00002. 155/2/69 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Chen S, Wang W, Lee S, Nafa K, Lee J, Romans K, et al. Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA. 2006;296(12):1479–87.  https://doi.org/10.1001/jama.296.12.1479.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Kastrinos F, Steyerberg EW, Mercado R, Balmana J, Holter S, Gallinger S, 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.  https://doi.org/10.1053/j.gastro.2010.08.021. S0016-5085(10)01239-4 [pii].CrossRefPubMedGoogle Scholar
  79. 79.
    Kastrinos F, Uno H, Ukaegbu C, Alvero C, McFarland A, Yurgelun MB, et al. Development and validation of the PREMM5 model for comprehensive risk assessment of Lynch syndrome. J Clin Oncol. 2017;35(19):2165–72.  https://doi.org/10.1200/JCO.2016.69.6120.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Dinh TA, Rosner BI, Atwood JC, Boland CR, Syngal S, Vasen HF, et al. Health benefits and cost-effectiveness of primary genetic screening for Lynch syndrome in the general population. Cancer Prev Res (Phila). 2011;4(1):9–22.  https://doi.org/10.1158/1940-6207.CAPR-10-0262. 1940-6207.CAPR-10-0262 [pii].CrossRefGoogle Scholar
  81. 81.
    Hitchins MP, Wong JJ, Suthers G, Suter CM, Martin DI, Hawkins NJ, et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med. 2007;356(7):697–705.  https://doi.org/10.1056/NEJMoa064522.CrossRefPubMedGoogle Scholar
  82. 82.
    Hitchins MP, Rapkins RW, Kwok CT, Srivastava S, Wong JJ, Khachigian LM, et al. Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5'UTR. Cancer Cell. 2011;20(2):200–13.  https://doi.org/10.1016/j.ccr.2011.07.003.CrossRefPubMedGoogle Scholar
  83. 83.
    Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K. American Society of Clinical O. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol : Off J Am Soc Clin Oncol. 2010;28(5):893–901.  https://doi.org/10.1200/JCO.2009.27.0660.CrossRefGoogle Scholar
  84. 84.
    Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, Guideline Development Group ACoMG, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17(1):70–87.  https://doi.org/10.1038/gim.2014.147.CrossRefPubMedGoogle Scholar
  85. 85.
    Lu KH, Wood ME, Daniels M, Burke C, Ford J, Kauff ND, et al. American Society of Clinical Oncology expert statement: collection and use of a cancer family history for oncology providers. J Clin Oncol: Off J Am Soc Clin Oncol. 2014;32(8):833–40.  https://doi.org/10.1200/JCO.2013.50.9257.CrossRefGoogle Scholar
  86. 86.
    Balmana J, Balaguer F, Cervantes A, Arnold D, Group EGW. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2013;24(Suppl 6):vi73–80.  https://doi.org/10.1093/annonc/mdt209.CrossRefPubMedGoogle Scholar
  87. 87.
    Douglas JA, et al. History and molecular genetics of Lynch syndrome in Family G. A century later. JAMA. 2005;294(17):2195–202.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of GastroenterologyUniversity of MichiganAnn ArborUSA
  2. 2.Dana-Farber Cancer Institute, Brigham & Women’s Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Division of GastroenterologyUCSD School of Medicine, University of CaliforniaSan DiegoUSA

Personalised recommendations