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Effective Identification of Lynch Syndrome in Gastroenterology Practice

  • Charles Muller
  • Lindsay Matthews
  • Sonia S. Kupfer
  • Jennifer M. WeissEmail author
Genetics in Gastroenterology Practice (B Katona, Section Editor)
  • 30 Downloads
Part of the following topical collections:
  1. Topical Collection on Genetics in Gastroenterology Practice

Abstract

Purpose of review

Identification of Lynch syndrome is important from an individual patient and public health standpoint. As paradigms for Lynch syndrome diagnosis have shifted in recent years, this review will discuss rationale and limitations for current strategies as well as provide an overview of future directions in the field.

Recent findings

In recent years, the use of clinical criteria and risk scores for identification of Lynch syndrome has been augmented by universal testing of all newly diagnosed colorectal cancers with molecular methods to screen for mismatch repair deficiency with high sensitivity and specificity. Studies of implementation and outcomes of universal testing in clinical practice have demonstrated significant heterogeneity that results in suboptimal uptake and contributes to disparities in diagnosis. Emerging technologies, such as next-generation sequencing, hold significant promise as a screening strategy for Lynch syndrome.

Summary

Universal testing for Lynch syndrome is being performed with increasing frequency, although real-world outcomes have demonstrated room for improvement. Future directions in Lynch syndrome diagnosis will involve optimization of universal testing workflow and application of new genetics technologies.

Keywords

Lynch syndrome Amsterdam Criteria Bethesda Guidelines PREMM Model Universal Tumor Screening 

Notes

Grant support

Support was provided in part by NIH R01 CA220329 (SSK) and grant MRSG-13-144-01-CPHPS from the American Cancer Society (JMW).

Compliance with ethical standards

Conflict of interest

Charles Muller and Lindsay Matthews declare no conflict of interest. Sonia Kupfer reports non-financial support from Myriad Genetics for collaborative research, outside the submitted work. Jennifer Weiss reports grants from American Cancer Society, during the conduct of the study; personal fees from American College of Physicians as an Editor of MKSAP 18 Board Basics Gastroenterology and Hepatology Section, outside the submitted work.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. 2010;138:2044–58.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 2008;135:1079–99.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138:2073–87.e3.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    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;137:1621–7.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bonadona V, Bonaïti 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;305:2304–10.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    • National Comprehensive Cancer Network. Genetic/familial high-risk assessment: Colorectal (Version 1.2018). Accessed August 27, 2019. Accessible at https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. The NCCN guidelines provide expert opinion on the evaluation and management of Lynch syndrome. These guidelines are updated annually
  7. 7.
    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;378:2081–7.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    • 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. Am J Gastroenterol. 2014;109:1159–79 Multi-society task force guidelines on genetic evaluation and management of Lynch syndrome with evidence-based recommendations. PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Järvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomäki P, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000;118:829–34.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    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;354:261–9.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Dove-Edwin I, Sasieni P, Adams J, Thomas HJ. Prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: 16 year, prospective, follow-up study. BMJ. 2005;331:1047.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    United Stated Department of Health and Human Services Healthy People 2020. In: Genomics. Accessed August 1, 2019. Accessible at https://www.healthypeople.gov/2020/topics-objectives/topic/genomics.
  13. 13.
    Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34:424–5.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    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;116:1453–6.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Barnetson RA, Tenesa A, Farrington SM, Nicholl ID, Cetnarskyj R, Porteous ME, et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med. 2006;354:2751–63.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    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;352:1851–60.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Salovaara R, Loukola A, Kristo P, Kaariainen H, Ahtola H, Eskelinen M, et al. Population-based molecular detection of hereditary nonpolyposis colorectal cancer. J Clin Oncol. 2000;18:2193–200.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Balmana J, Balaguer F, Castellvi-Bel S, Steyerberg EW, Andreu M, Llor X, et al. Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients. J Med Genet. 2008;45:557–63.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Green RC, Parfrey PS, Woods MO, Younghusband HB. Prediction of Lynch syndrome in consecutive patients with colorectal cancer. J Natl Cancer Inst. 2009;101:331–40.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    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;89:1758–62.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    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;96:261–8.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    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;58:5248–57.Google Scholar
  23. 23.
    Niessen RC, Hofstra RM, Westers H, Ligtenberg MJ, Kooi K, Jager PO, et al. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome. Genes Chromosom Cancer. 2009;48:737–44.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomaki P, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med. 1998;338:1481–7.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Lamberti C, Kruse R, Ruelfs C, Caspari R, Wang Y, Jungck M, et al. Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer. Gut. 1999;44:839–43.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Pinol V, Castells A, Andreu M, Castellvi-Bel S, Alenda C, Llor X, et al. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005;293:1986–94.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Terdiman JP, Gum JR Jr, Conrad PG, Miller GA, Weinberg V, Crawley SC, et al. Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing. Gastroenterology. 2001;120:21–30.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Syngal S, Fox EA, Eng C, Kolodner RD, Garber JE. Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet. 2000;37:641–5.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Grover S, Stoffel EM, Bussone L, Tschoegl E, Syngal S. Physician assessment of family cancer history and referral for genetic evaluation in colorectal cancer patients. Clin Gastroenterol Hepatol. 2004;2:813–9.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Kupfer SS, McCaffrey S, Kim KE. Racial and gender disparities in hereditary colorectal cancer risk assessment: the role of family history. J Cancer Educ. 2006;21:S32–6.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Kastrinos F, Allen JI, Stockwell DH, Stoffel EM, Cook EF, Mutinga ML, et al. Development and validation of a colon cancer risk assessment tool for patients undergoing colonoscopy. Am J Gastroenterol. 2009;104:1508–18.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Gunaratnam NT, Akce M, Al Natour R, Bartley AN, Fioritto AF, Hanson K, et al. Screening for Cancer Genetic Syndromes With a Simple Risk-Assessment Tool in a Community-Based Open-Access Colonoscopy Practice. Am J Gastroenterol. 2016;111:589–93.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Guivatchian T, Koeppe ES, Baker JR, Moisa C, Demerath M, Foor-Pessin C, et al. Family history in colonoscopy patients: feasibility and performance of electronic and paper-based surveys for colorectal cancer risk assessment in the outpatient setting. Gastrointest Endosc. 2017;86:684–91.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Win AK, Macinnis RJ, Dowty JG, Jenkins MA. Criteria and prediction models for mismatch repair gene mutations: a review. J Med Genet. 2013;50:785–93.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Tresallet C, Brouquet A, Julie C, Beauchet A, Vallot C, Menegaux F, et al. Evaluation of predictive models in daily practice for the identification of patients with Lynch syndrome. Int J Cancer. 2012;130:1367–77.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Chen S, Wang W, Lee S, Nafa K, Lee J, Romans K, et al. Colon Cancer Family Registry. Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA. 2006;296:1479–87.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Balmana J, Stockwell DH, Steyerberg EW, Stoffel EM, Deffenbaugh AM, Reid JE, et al. Prediction of MLH1 and MSH2 mutations in Lynch syndrome. JAMA. 2006;296:1469–78.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    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;140:73–81.PubMedCrossRefGoogle Scholar
  39. 39.
    •• 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;35:2165–72 Validation of PREMM5 model for identification of Lynch syndrome risk using data from over 18,000 tested individuals and validated in over 1,000 individuals. PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Khan O, Blanco A, Conrad P, Gulden C, Moss TZ, Olopade OI, et al. Performance of Lynch syndrome predictive models in a multi-center US referral population. Am J Gastroenterol. 2011;106:1822–7.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Mercado RC, Hampel H, Kastrinos F, Steyerberg E, Balmana J, Stoffel E, et al. Performance of PREMM(1,2,6), MMRpredict, and MMRpro in detecting Lynch syndrome among endometrial cancer cases. Genet Med. 2012;14:670–80.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Balaguer F, Balmana J, Castellvi-Bel S, Steyerberg EW, Andreu M, Llor X, et al. Validation and extension of the PREMM1,2 model in a population-based cohort of colorectal cancer patients. Gastroenterology. 2008;134:39–46.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Kastrinos F, Steyerberg EW. Family matters in lynch syndrome. J Natl Cancer Inst. 2015;107.Google Scholar
  44. 44.
    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;26:5783–8.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Shields HM, Stoffel EM, Chung DC, Sequist TD, Li JW, Pelletier SR, et al. Disparities in evaluation of patients with rectal bleeding 40 years and older. Clin Gastroenterol Hepatol. 2014;12:669–75.quiz e33.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Parsons MT, Buchanan DD, Thompson B, Young JP, Spurdle AB. Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet. 2012;49:151–7.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Gelsomino F, Barbolini M, Spallanzani A, Pugliese G, Cascinu S. The evolving role of microsatellite instability in colorectal cancer: A review. Cancer Treat Rev. 2016;51:19–26.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Pearlman R, Hampel H, de la Chepelle A, Goldberg R, Ciombor K, Arnold M, et al. Ohio colorectal cancer prevention initiative. Familial Cancer. 2017;16:S48.Google Scholar
  49. 49.
    Prasad V, Kaestner V, Mailankody S. Cancer Drugs Approved Based on Biomarkers and Not Tumor Type-FDA Approval of Pembrolizumab for Mismatch Repair-Deficient Solid Cancers. JAMA Oncol. 2018;4:157–8.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Beamer LC, Grant ML, Espenschied CR, Blazer KR, Hampel HL, Weitzel JN, et al. 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;30:1058–63.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    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;11:42–65.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787–93.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, et al. Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer. JAMA Oncol. 2017;3:464–71.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Hampel H, Pearlman R, Beightol M, Zhao W, Jones D, Frankel WL, et al. Assessment of Tumor Sequencing as a Replacement for Lynch Syndrome Screening and Current Molecular Tests for Patients With Colorectal Cancer. JAMA Oncol. 2018;4:806–13.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Shia J, Stadler Z, Weiser MR, Rentz M, Gonen M, Tang LH, et al. Immunohistochemical staining for DNA mismatch repair proteins in intestinal tract carcinoma: how reliable are biopsy samples? Am J Surg Pathol. 2011;35:447–54.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Cavazza A, Radia C, Harlow C, Monahan KJ. Experience of the implementation and outcomes of universal testing for Lynch syndrome in the United Kingdom. Color Dis. 2019;21:760–6.Google Scholar
  57. 57.
    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.CrossRefGoogle Scholar
  58. 58.
    Li D, Hoodfar E, Jiang SF, Udaltsova N, Pham NP, Jodesty Y, et al. Comparison of Universal Versus Age-Restricted Screening of Colorectal Tumors for Lynch Syndrome Using Mismatch Repair Immunohistochemistry: A Cohort Study. Ann Intern Med. 2019.Google Scholar
  59. 59.
    Bellcross CA, Bedrosian SR, Daniels E, Duquette D, Hampel H, Jasperson K, et al. Implementing screening for Lynch syndrome among patients with newly diagnosed colorectal cancer: summary of a public health/clinical collaborative meeting. Genet Med. 2012;14:152–62.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    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;308:1555–65.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Di Marco M, DAndrea E, Panic N, Baccolini V, Migliara G, Marzuillo C, et al. Which Lynch syndrome screening programs could be implemented in the "real world"? A systematic review of economic evaluations. Genet Med. 2018;20:1131–44.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Mvundura M, Grosse SD, Hampel H, Palomaki GE. The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genet Med. 2010;12:93–104.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    •• 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;155:69–79 This paper examines the cost-effectiveness of universal tumor screening for Lynch syndrome. PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Dotson WD, Douglas MP, Kolor K, Stewart AC, Bowen MS, Gwinn M, et al. Prioritizing genomic applications for action by level of evidence: a horizon-scanning method. Clin Pharmacol Ther. 2014;95:394–402.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Weissman SM, Burt R, Church J, Erdman S, Hampel H, Holter S, et al. Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline. J Genet Couns. 2012;21:484–93.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    • Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110:223–62 American College of Gastroenterology guidelines on evaluation of hereditary gastrointestinal cancer syndromes including Lynch syndrome. PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Shaikh T, Handorf EA, Meyer JE, Hall MJ, Esnaola NF. Mismatch Repair Deficiency Testing in Patients With Colorectal Cancer and Nonadherence to Testing Guidelines in Young Adults. JAMA Oncol. 2018;4:e173580.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Karlitz JJ, Hsieh MC, Liu Y, Blanton C, Schmidt B, Jessup JM, et al. Population-Based Lynch Syndrome Screening by Microsatellite Instability in Patients ≤50: Prevalence, Testing Determinants, and Result Availability Prior to Colon Surgery. Am J Gastroenterol. 2015;110:948–55.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Muller C, Lee SM, Barge W, Siddique SM, Berera S, Wideroff G, et al. Low Referral Rate for Genetic Testing in Racially and Ethnically Diverse Patients Despite Universal Colorectal Cancer Screening. Clin Gastroenterol Hepatol. 2018;16:1911–8.e2.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Jain A, Shafer L, Rothenmund H, Kim CA, Samadder J, Gupta S, et al. Suboptimal Adherence in Clinical Practice to Guidelines Recommendation to Screen for Lynch Syndrome. Dig Dis Sci. 2019.Google Scholar
  71. 71.
    Cohen SA. Current Lynch syndrome tumor screening practices: a survey of genetic counselors. J Genet Couns. 2014;23:38–47.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Schneider JL, Davis J, Kauffman TL, Reiss JA, McGinley C, Arnold K, et al. Stakeholder perspectives on implementing a universal Lynch syndrome screening program: a qualitative study of early barriers and facilitators. Genet Med. 2016;18:152–61.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Dicks E, Pullman D, Kao K, MacMillan A, Logan GS, Simmonds C, et al. Universal tumor screening for Lynch syndrome: Perceptions of Canadian pathologists and genetic counselors of barriers and facilitators. Cancer Med. 2019;8:3614–22.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Guindalini RS, Win AK, Gulden C, Lindor NM, Newcomb PA, Haile RW, et al. Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome. Gastroenterology. 2015;149:1446–53.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Ricker CN, Hanna DL, Peng C, Nguyen NT, Stern MC, Schmit SL, et al. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer. Cancer. 2017;123:3732–43.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Hall MJ, Olopade OI. Disparities in genetic testing: thinking outside the BRCA box. J Clin Oncol. 2006;24:2197–203.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    O'Kane GM, Ryan É, McVeigh TP, Creavin B, Hyland JM, O'Donoghue DP, et al. Screening for mismatch repair deficiency in colorectal cancer: data from three academic medical centers. Cancer Med. 2017;6:1465–72.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Heald B, Plesec T, Liu X, Pai R, Patil D, Moline J, et al. Implementation of universal microsatellite instability and immunohistochemistry screening for diagnosing lynch syndrome in a large academic medical center. J Clin Oncol. 2013;31:1336–40.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Frolova AI, Babb SA, Zantow E, Hagemann AR, Powell MA, Thaker PH, et al. Impact of an immunohistochemistry-based universal screening protocol for Lynch syndrome in endometrial cancer on genetic counseling and testing. Gynecol Oncol. 2015;137:7–13.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Papke DJ, Nowak JA, Yurgelun MB, Frieden A, Srivastava A, Lindeman NI, et al. Validation of a targeted next-generation sequencing approach to detect mismatch repair deficiency in colorectal adenocarcinoma. Mod Pathol. 2018;31:1882–90.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Nowak JA, Yurgelun MB, Bruce JL, Rojas-Rudilla V, Hall DL, Shivdasani P, et al. Detection of Mismatch Repair Deficiency and Microsatellite Instability in Colorectal Adenocarcinoma by Targeted Next-Generation Sequencing. J Mol Diagn. 2017;19:84–91.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Stadler ZK, Battaglin F, Middha S, Hechtman JF, Tran C, Cercek A, et al. Reliable Detection of Mismatch Repair Deficiency in Colorectal Cancers Using Mutational Load in Next-Generation Sequencing Panels. J Clin Oncol. 2016;34:2141–7.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    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;372:2509–20.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Pritchard CC, Salipante SJ, Koehler K, Smith C, Scroggins S, Wood B, et al. Validation and implementation of targeted capture and sequencing for the detection of actionable mutation, copy number variation, and gene rearrangement in clinical cancer specimens. J Mol Diagn. 2014;16:56–67.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Christakis AG, Papke DJ, Nowak JA, Yurgelun MB, Agoston AT, Lindeman NI, et al. Targeted Cancer Next-Generation Sequencing as a Primary Screening Tool for Microsatellite Instability and Lynch Syndrome in Upper Gastrointestinal Tract Cancers. Cancer Epidemiol Biomark Prev. 2019;28:1246–51.CrossRefGoogle Scholar
  86. 86.
    Chubak B, Heald B, Sharp RR. Informed consent to microsatellite instability and immunohistochemistry screening for Lynch syndrome. Genet Med. 2011;13:356–60.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Colon Cancer Genetics Group. University of Edinburgh and MRC Human genetics Unit, Edinburgh. Prediction of DNA mismatch repair gene mutation status in incident colorectal cancer cases. Accessed August 16, 2019. Accessible at http://hnpccpredict.hgu.mrc.ac.uk/.
  88. 88.
    BayesMendel Lab. Harvard University. MMRpro. Accessed August 16, 2019. Accessible at https://projects.iq.harvard.edu/bayesmendel/mmrpro.
  89. 89.
    Dana-Farber Cancer Institute. PREMM. Lynch syndrome prediction model. MLH1, MSH2, MSH6, PMS2, and EPCAM gene mutations. Accessed August 16, 2019. Accessible at https://premm.dfci.harvard.edu/.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Charles Muller
    • 1
  • Lindsay Matthews
    • 2
  • Sonia S. Kupfer
    • 1
  • Jennifer M. Weiss
    • 2
    • 3
    Email author
  1. 1.Section of Gastroenterology, Hepatology and Nutrition, Department of MedicineUniversity of ChicagoChicagoUSA
  2. 2.Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  3. 3.Division of Gastroenterology and Hepatology, Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA

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