{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:25:12Z","timestamp":1773660312797,"version":"3.50.1"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2014,5,15]],"date-time":"2014-05-15T00:00:00Z","timestamp":1400112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr. Treat. Options in Oncol."],"published-print":{"date-parts":[[2014,9]]},"DOI":"10.1007\/s11864-014-0293-5","type":"journal-article","created":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T01:37:00Z","timestamp":1400031420000},"page":"429-442","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genetics, Biomarkers, Hereditary Cancer Syndrome Diagnosis, Heterogeneity and Treatment: A Review"],"prefix":"10.1007","volume":"15","author":[{"given":"Henry T.","family":"Lynch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Drescher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Knezetic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Lanspa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,5,15]]},"reference":[{"key":"293_CR1","unstructured":"Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer. Available at: http:\/\/www-dep.iarc.fr . Accessed August 30, 2012."},{"key":"293_CR2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3322\/caac.21208","volume":"64","author":"R Siegel","year":"2014","unstructured":"Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9\u201329.","journal-title":"CA Cancer J Clin"},{"key":"293_CR3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-0004.2009.01230.x","volume":"76","author":"HT Lynch","year":"2009","unstructured":"Lynch HT, Lynch PM, Lanspa SJ, et al. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76:1\u201318.","journal-title":"Clin Genet"},{"key":"293_CR4","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.1200\/JCO.2008.17.5950","volume":"26","author":"H Hampel","year":"2008","unstructured":"Hampel H, Frankel WL, Martin E, et al. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008;26:5783\u20138.","journal-title":"J Clin Oncol"},{"key":"293_CR5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/GIM.0b013e31818fa2ff","volume":"11","author":"Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group","year":"2009","unstructured":"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\u201341.","journal-title":"Genet Med"},{"key":"293_CR6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.2302\/kjm.56.14","volume":"56","author":"NO Davidson","year":"2007","unstructured":"Davidson NO. Genetic testing in colorectal cancer: who, when, how and why. Keio J Med. 2007;56:14\u201320.","journal-title":"Keio J Med"},{"key":"293_CR7","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1200\/JCO.2006.10.3119","volume":"25","author":"HT Lynch","year":"2007","unstructured":"Lynch HT, Boland CR, Rodriguez-Bigas MA, et al. Who should be sent for genetic testing in hereditary colorectal cancer syndromes? J Clin Oncol. 2007;25:3534\u201342.","journal-title":"J Clin Oncol"},{"key":"293_CR8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1634\/theoncologist.2013-0392","volume":"19","author":"SD Ramsey","year":"2014","unstructured":"Ramsey SD, Sullivan SD. A new model for reimbursing genome-based cancer care. Oncologist. 2014;19:1\u20134.","journal-title":"Oncologist"},{"key":"293_CR9","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","volume":"45","author":"N Cancer Genome Atlas Research","year":"2013","unstructured":"Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013;45:1113\u201320. This paper demonstrates some of the important work being done by the Cancer Genome Atlas Research Network aimed at increasing the efficacy of cancer therapy.","journal-title":"Nat Genet"},{"key":"293_CR10","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.molonc.2013.04.008","volume":"7","author":"S Kamalakaran","year":"2013","unstructured":"Kamalakaran S, Varadan V, Janevski A, et al. Translating next generation sequencing to practice: opportunities and necessary steps. Mol Oncol. 2013;7:743\u201355.","journal-title":"Mol Oncol"},{"key":"293_CR11","unstructured":"U.S. Food and Drug Administration: Table of pharmacogenomic biomarkers in drug labeling. Available at: http:\/\/www.fda.gov\/drugs\/scienceresearch\/researchareas\/Pharmacogenetics\/ucm083378.htm . Accessed January 31, 2014."},{"key":"293_CR12","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1053\/j.gastro.2013.12.002","volume":"146","author":"AR Mensenkamp","year":"2014","unstructured":"Mensenkamp AR, Vogelaar IP, van Zelst-Stams WAG, et al. Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology. 2014;146:643\u20136.","journal-title":"Gastroenterology"},{"key":"293_CR13","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1053\/j.gastro.2014.01.041","volume":"146","author":"JM Carethers","year":"2014","unstructured":"Carethers JM. Differentiating Lynch-like from Lynch syndrome. Gastroenterology. 2014;146:602\u20134. This commentary pulls together the current thinking on the newly identified \u201cLynch-like\u201d colorectal cancer and how it differs from Lynch syndrome.","journal-title":"Gastroenterology"},{"key":"293_CR14","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1136\/jmg.2009.068122","volume":"46","author":"MP Hitchins","year":"2009","unstructured":"Hitchins MP, Ward RL. Constitutional (germline) MLH1 epimutation as an aetiological mechanism for hereditary non-polyposis colorectal cancer. J Med Genet. 2009;46:793\u2013802.","journal-title":"J Med Genet"},{"key":"293_CR15","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1097\/01.sla.0000246937.54435.50","volume":"244","author":"JH Lefevre","year":"2006","unstructured":"Lefevre JH, Rodrigue CM, Mourra N, et al. Implication of MYH in colorectal polyposis. Ann Surg. 2006;244:874\u201380.","journal-title":"Ann Surg"},{"key":"293_CR16","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/ijc.23508","volume":"123","author":"P Watson","year":"2008","unstructured":"Watson P, Vasen HFA, Mecklin J-P, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer. 2008;123:444\u20139.","journal-title":"Int J Cancer"},{"key":"293_CR17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/ng.283","volume":"41","author":"MJL Ligtenberg","year":"2009","unstructured":"Ligtenberg MJL, Kuiper RP, Chan TL, 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;41:112\u20137.","journal-title":"Nat Genet"},{"key":"293_CR18","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/ajg.2011.203","volume":"106","author":"H Lynch","year":"2011","unstructured":"Lynch H, Riegert-Johnson D, Snyder C, et al. Lynch syndrome associated extracolonic tumors are rare in two extended families with the same EPCAM deletion. Am J Gastroenterol. 2011;106:1829\u201336.","journal-title":"Am J Gastroenterol"},{"key":"293_CR19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1470-2045(10)70265-5","volume":"12","author":"MJE Kempers","year":"2011","unstructured":"Kempers MJE, Kuiper RP, Ockeloen CW, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol. 2011;12:49\u201355.","journal-title":"Lancet Oncol"},{"key":"293_CR20","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1001\/jama.293.16.1979","volume":"293","author":"NM Lindor","year":"2005","unstructured":"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;293:1979\u201385.","journal-title":"JAMA"},{"key":"293_CR21","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/path.2573","volume":"219","author":"AM Ferreira","year":"2009","unstructured":"Ferreira AM, Westers H, Sousa S, et al. Mononucleotide precedes dinucleotide repeat instability during colorectal tumour development in Lynch syndrome patients. J Pathol. 2009;219:96\u2013102.","journal-title":"J Pathol"},{"key":"293_CR22","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.cgh.2007.10.011","volume":"6","author":"X Bessa","year":"2008","unstructured":"Bessa X, Balleste B, Andreu M, et al. A prospective, multicenter, population-based study of BRAF mutational analysis for Lynch syndrome screening. Clin Gastroenterol Hepatol. 2008;6:206\u201314.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"293_CR23","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1136\/gut.42.5.673","volume":"42","author":"JR Jass","year":"1998","unstructured":"Jass JR, Do K-A, Simms LA, et al. Morphology of sporadic colorectal cancer with DNA replication errors. Gut. 1998;42:673\u20139.","journal-title":"Gut"},{"key":"293_CR24","volume-title":"Tumours of the Digestive System","year":"2000","unstructured":"Hamilton SR, Aaltonen LA, editors. Tumours of the Digestive System. Lyon: IARC Press; 2000."},{"key":"293_CR25","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1053\/gast.2001.29616","volume":"121","author":"Y Miyakura","year":"2001","unstructured":"Miyakura Y, Sugano K, Konishi F, et al. Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability. Gastroenterology. 2001;121:1300\u20139.","journal-title":"Gastroenterology"},{"key":"293_CR26","first-page":"6991","volume":"61","author":"H Nakagawa","year":"2001","unstructured":"Nakagawa H, Nuovo GJ, Zervos EE, et al. Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucousa is associated with microsatellite-unstable colorectal cancer development. Cancer Res. 2001;61:6991\u20135.","journal-title":"Cancer Res"},{"key":"293_CR27","doi-asserted-by":"crossref","first-page":"8698","DOI":"10.1073\/pnas.95.15.8698","volume":"95","author":"ML Veigl","year":"1998","unstructured":"Veigl ML, Kasturi L, Olechnowicz J, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci. 1998;95:8698\u2013702.","journal-title":"Proc Natl Acad Sci"},{"key":"293_CR28","doi-asserted-by":"crossref","first-page":"6870","DOI":"10.1073\/pnas.95.12.6870","volume":"95","author":"JG Herman","year":"1998","unstructured":"Herman JG, Umar A, Polyak K, et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci. 1998;95:6870\u20135.","journal-title":"Proc Natl Acad Sci"},{"key":"293_CR29","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1053\/j.gastro.2008.07.076","volume":"135","author":"WM Grady","year":"2008","unstructured":"Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 2008;135:1079\u201399.","journal-title":"Gastroenterology"},{"key":"293_CR30","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1056\/NEJMoa043146","volume":"352","author":"H Hampel","year":"2005","unstructured":"Hampel H, Frankel WL, Martin E, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005;352:1851\u201360.","journal-title":"N Engl J Med"},{"key":"293_CR31","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.cgh.2013.12.007","volume":"12","author":"JM Carethers","year":"2014","unstructured":"Carethers JM. DNA testing and molecular screening for colon cancer. Clin Gastroenterol Hepatol. 2014;12:377\u201381.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"293_CR32","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1053\/j.gastro.2013.01.044","volume":"144","author":"M Rodriguez-Soler","year":"2013","unstructured":"Rodriguez-Soler M, Perez-Carbonell L, Guarinos C, et al. Risk of cancer in cases of suspected lynch syndrome without germline mutation. Gastroenterology. 2013;144:926\u201332. This is an up-to-date study of cancer risk in suspected Lynch syndrome without an identified germline mutation.","journal-title":"Gastroenterology"},{"key":"293_CR33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10689-012-9568-9","volume":"12","author":"I Sourrouille","year":"2013","unstructured":"Sourrouille I, Coulet F, Lefevre JH, et al. Somatic mosaicism and double somatic hits can lead to MSI colorectal tumors. Fam Cancer. 2013;12:27\u201333.","journal-title":"Fam Cancer"},{"key":"293_CR34","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1053\/j.gastro.2013.03.014","volume":"144","author":"CR Boland","year":"2013","unstructured":"Boland CR. The mystery of mismatch repair deficiency: Lynch or Lynch-like? Gastroenterology. 2013;144:869.","journal-title":"Gastroenterology"},{"key":"293_CR35","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1158\/1055-9965.EPI-08-0512","volume":"17","author":"JN Poynter","year":"2008","unstructured":"Poynter JN, Siegmund KD, Weisenberger DJ, et al. Molecular characterization of MSI-H colorectal cancer by MLH1 promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening. Cancer Epidemiol Biomarkers Prev. 2008;17:3208\u201315.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"293_CR36","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1158\/1078-0432.CCR-06-3064","volume":"13","author":"M Bettstetter","year":"2007","unstructured":"Bettstetter M, Dechant S, Ruemmele P, et al. Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR. Clin Cancer Res. 2007;13:3221\u20138.","journal-title":"Clin Cancer Res"},{"key":"293_CR37","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/labinvest.3780262","volume":"81","author":"S Salahshor","year":"2001","unstructured":"Salahshor S, Koeble K, Rubio C, et al. Microsatellite instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer. Lab Investig. 2001;81:535\u201341.","journal-title":"Lab Investig"},{"key":"293_CR38","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1200\/JCO.20.4.1043","volume":"20","author":"NM Lindor","year":"2002","unstructured":"Lindor NM, Burgart LJ, Leontovich O, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol. 2002;20:1043\u20138.","journal-title":"J Clin Oncol"},{"key":"293_CR39","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1136\/jmg.2004.020651","volume":"41","author":"E Domingo","year":"2004","unstructured":"Domingo E, Laiho P, Ollikainen M, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41:664\u20138.","journal-title":"J Med Genet"},{"key":"293_CR40","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.suc.2008.04.006","volume":"88","author":"HT Lynch","year":"2008","unstructured":"Lynch HT, Silva E, Wirtzfeld D, et al. Hereditary diffuse gastric cancer: prophylactic surgical oncology implications. Surg Clin N Am. 2008;88:759\u201378.","journal-title":"Surg Clin N Am"},{"key":"293_CR41","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/363558a0","volume":"363","author":"YM Ionov","year":"1993","unstructured":"Ionov YM, Peinado MA, Malkhosyan S, et al. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363:558\u201361.","journal-title":"Nature"},{"key":"293_CR42","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1093\/jnci\/89.23.1758","volume":"89","author":"MA Rodriguez-Bigas","year":"1997","unstructured":"Rodriguez-Bigas MA, Boland CR, Hamilton SR, 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\u201362.","journal-title":"J Natl Cancer Inst"},{"key":"293_CR43","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djh034","volume":"96","author":"A Umar","year":"2004","unstructured":"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;96:261\u20138.","journal-title":"J Natl Cancer Inst"},{"key":"293_CR44","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/gutjnl-2011-300041","volume":"61","author":"L P\u00e9rez-Carbonell","year":"2012","unstructured":"P\u00e9rez-Carbonell L, Ruiz-Ponte C, Guarinos C, et al. Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients wtih colorectal cancer. Gut. 2012;61:865\u201372.","journal-title":"Gut"},{"key":"293_CR45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/GIM.0b013e3181cd666c","volume":"12","author":"M Mvundura","year":"2010","unstructured":"Mvundura M, Grosse SD, Hampel H, et al. The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genet Med. 2010;12:93\u2013104.","journal-title":"Genet Med"},{"key":"293_CR46","doi-asserted-by":"crossref","first-page":"69","DOI":"10.7326\/0003-4819-155-2-201107190-00002","volume":"155","author":"U Ladabaum","year":"2011","unstructured":"Ladabaum U, Wang G, Terdiman J, et al. Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med. 2011;155:69\u201379.","journal-title":"Ann Intern Med"},{"key":"293_CR47","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1200\/JCO.2012.45.1674","volume":"31","author":"B Heald","year":"2013","unstructured":"Heald B, Plesec T, Liu X, et al. Implementation of universal microsatellite instability and immunohistochemistry screening for diagnosing Lynch syndrome in a large acadmic medical center. J Clin Oncol. 2013;31:1336\u201340.","journal-title":"J Clin Oncol"},{"key":"293_CR48","unstructured":"U S Department of Health and Human Services: Healthy People 2020 Topics and Objectives: Genomics. Available at: http:\/\/healthypeople.gov\/2020\/topicsobjectives2020\/overview.aspx?topicid=15 . Accessed April 16, 2013."},{"key":"293_CR49","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1463-1318.2008.01702.x","volume":"11","author":"DA Stupart","year":"2009","unstructured":"Stupart DA, Goldberg PA, Algar U, et al. Surveillance colonoscopy improves survival in a cohort of subjects with a single mismatch repair gene mutation. Color Dis. 2009;11:126\u201330.","journal-title":"Color Dis"},{"key":"293_CR50","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0016-5085(00)70168-5","volume":"118","author":"HJ J\u00e4rvinen","year":"2000","unstructured":"J\u00e4rvinen 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;118:829\u201334.","journal-title":"Gastroenterology"},{"key":"293_CR51","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1053\/j.gastro.2005.11.032","volume":"130","author":"AE Jong de","year":"2006","unstructured":"de Jong AE, Hendriks YMC, Kleibeuker JH, et al. Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology. 2006;130:665\u201371.","journal-title":"Gastroenterology"},{"key":"293_CR52","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1200\/JCO.2009.23.7784","volume":"27","author":"HJ J\u00e4rvinen","year":"2009","unstructured":"J\u00e4rvinen HJ, Renkonen-Sinisalo L, Akt\u00e1n-Coll\u00e1n K, et al. Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol. 2009;27:4793\u20137.","journal-title":"J Clin Oncol"},{"key":"293_CR53","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1002\/1097-0142(20010615)91:12<2417::AID-CNCR1276>3.0.CO;2-U","volume":"91","author":"TC Smyrk","year":"2001","unstructured":"Smyrk TC, Watson P, Kaul K, et al. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal cancer. Cancer. 2001;91:2417\u201322.","journal-title":"Cancer"},{"key":"293_CR54","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1053\/j.gastro.2008.01.015","volume":"134","author":"Y Schwitalle","year":"2008","unstructured":"Schwitalle Y, Kloor M, Eiermann S, et al. Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology. 2008;134:988\u201397.","journal-title":"Gastroenterology"},{"key":"293_CR55","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1001\/archsurg.2012.35","volume":"147","author":"JW Huh","year":"2012","unstructured":"Huh JW, Lee HG, Kim HR. Prognostic significance of tumor-infiltrating lymphocytes for patients with colorectal cancer. Arch Surg. 2012;147:366\u201371. This is a recent investigation of prognostic significance of tumor-infiltrating lymphocytes in colorectal cancer patients.","journal-title":"Arch Surg"},{"key":"293_CR56","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1200\/JCO.2011.41.0902","volume":"31","author":"S Loi","year":"2013","unstructured":"Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02\u201398. J Clin Oncol. 2013;31:860\u20137.","journal-title":"J Clin Oncol"},{"key":"293_CR57","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10689-013-9633-z","volume":"12","author":"N Devaud","year":"2013","unstructured":"Devaud N, Gallinger S. Chemotherapy of MMR-deficient colorectal cancer. Fam Cancer. 2013;12:301\u20136. This is an up-to-date overview of the effect of chemotherapy in mismatch repair-deficient colorectal cancer.","journal-title":"Fam Cancer"},{"key":"293_CR58","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.ejca.2011.10.005","volume":"48","author":"SP Hong","year":"2012","unstructured":"Hong SP, Min BS, Kim TI, et al. The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer. Eur J Cancer. 2012;48:1235\u201343.","journal-title":"Eur J Cancer"},{"key":"293_CR59","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1016\/j.ejca.2010.05.009","volume":"46","author":"C Guastadisegni","year":"2010","unstructured":"Guastadisegni C, Colafranceschi M, Ottini L, et al. Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data. Eur J Cancer. 2010;46:2788\u201398.","journal-title":"Eur J Cancer"},{"key":"293_CR60","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/jnci\/djr153","volume":"103","author":"FA Sinicrope","year":"2011","unstructured":"Sinicrope FA, Foster NR, Thibodeau SN, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst. 2011;103:863\u201375. This is an important study on 5-fluorouracil-based adjuvant therapy in relation to mismatch repair status. Although there has been some criticism of the study's selection of subjects, its results are still noteworthy as the only study to date that has investigated the difference in chemotherapy results between Lynch syndrome colorectal cancer and sporadic microsatellite instability-high colorectal cancer.","journal-title":"J Natl Cancer Inst"},{"key":"293_CR61","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/ijc.11712","volume":"109","author":"WH Vos tot Nederveen Cappel de","year":"2004","unstructured":"de Vos tot Nederveen Cappel WH, Meulenbeld HJ, Kleibeuker JH, et al. Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer. Int J Cancer. 2004;109:468\u201371.","journal-title":"Int J Cancer"},{"key":"293_CR62","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00280-009-1206-3","volume":"66","author":"ST Kim","year":"2010","unstructured":"Kim ST, Lee J, Park SH, et al. Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy. Cancer Chemother Pharmacol. 2010;66:659\u201367.","journal-title":"Cancer Chemother Pharmacol"},{"key":"293_CR63","doi-asserted-by":"crossref","first-page":"7470","DOI":"10.1158\/1078-0432.CCR-11-1048","volume":"17","author":"A Zaanan","year":"2011","unstructured":"Zaanan A, Fl\u00e9jou J-F, Emile J-F, et al. Defective mismatch repair status as a prognostic biomarker of disease-free survival in stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy. Clin Cancer Res. 2011;17:7470\u20138.","journal-title":"Clin Cancer Res"},{"key":"293_CR64","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.1200\/JCO.2013.48.9591","volume":"31","author":"FA Sinicrope","year":"2013","unstructured":"Sinicrope FA, Mahoney MR, Smyrk TC, et al. Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol. 2013;31:3664\u201372.","journal-title":"J Clin Oncol"},{"key":"293_CR65","first-page":"4881","volume":"56","author":"D Fink","year":"1996","unstructured":"Fink D, Nebel S, Aebi S, et al. The role of DNA mismatch repair in platinum drug resistance. Cancer Res. 1996;56:4881\u20136.","journal-title":"Cancer Res"},{"key":"293_CR66","doi-asserted-by":"crossref","first-page":"6531","DOI":"10.1158\/1078-0432.CCR-12-0605","volume":"18","author":"PG Gavin","year":"2012","unstructured":"Gavin PG, Colangelo LH, Fumagalli D, et al. Mutation profiling and microsatellite instability in stage II and stage III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res. 2012;18:6531\u201341.","journal-title":"Clin Cancer Res"},{"key":"293_CR67","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1056\/NEJMoa0801297","volume":"359","author":"J Burn","year":"2008","unstructured":"Burn J, Bishop T, Mecklin J-P, et al. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome. N Engl J Med. 2008;359:2567\u201378.","journal-title":"N Engl J Med"},{"key":"293_CR68","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/S0140-6736(11)61049-0","volume":"378","author":"J Burn","year":"2011","unstructured":"Burn J, Gerdes A-M, Macrae F, 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\u20137. This study demonstrates the importance of investigating long-term effects of chemoprevention\u2014in this case, use of aspirin, which was not found to have a beneficial short-term effect on carriers of hereditary colorectal cancer mutations but was found to carry long-term benefits.","journal-title":"Lancet"},{"key":"293_CR69","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1200\/JCO.2013.52.0080","volume":"31","author":"CS Fuchs","year":"2013","unstructured":"Fuchs CS, Ogino S. Aspirin therapy for colorectal cancer with PIK3CA mutation: simply complex! J Clin Oncol. 2013;31:4358\u201361. This paper elucidates what is known about aspirin therapy in colorectal cancer based on PIK3CA mutation status.","journal-title":"J Clin Oncol"},{"key":"293_CR70","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1056\/NEJMoa021735","volume":"348","author":"JA Baron","year":"2003","unstructured":"Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891\u20139.","journal-title":"N Engl J Med"},{"key":"293_CR71","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1053\/j.gastro.2006.08.079","volume":"131","author":"JA Baron","year":"2006","unstructured":"Baron JA, Sandler RS, Bresalier RS, et al. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology. 2006;131:1674\u201382.","journal-title":"Gastroenterology"},{"key":"293_CR72","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1053\/j.gastro.2007.10.014","volume":"134","author":"RF Logan","year":"2008","unstructured":"Logan RF, Grainge MJ, Shepherd VC, et al. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology. 2008;134:29\u201338.","journal-title":"Gastroenterology"},{"key":"293_CR73","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.1200\/JCO.2013.50.0322","volume":"31","author":"E Domingo","year":"2013","unstructured":"Domingo E, Church DN, Sieber O, et al. Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer. J Clin Oncol. 2013;31:4297\u2013305.","journal-title":"J Clin Oncol"},{"key":"293_CR74","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1056\/NEJMoa1207756","volume":"367","author":"X Liao","year":"2012","unstructured":"Liao X, Lochhead P, Nishihara R, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med. 2012;367:1596\u2013606. This study looks at the effect of aspirin use on colorectal cancer survival in relation to a number of molecular genetic variations with important results regarding PIK3CA mutation status.","journal-title":"N Engl J Med"},{"key":"293_CR75","first-page":"12","volume":"1","author":"A Amatu","year":"2013","unstructured":"Amatu A, Bencardino K, Sartore-Bianchi A, et al. Aspirin for colorectal cancer with PIK3CA mutations: the rising of the oldest targeted therapy? Ann Transl Med. 2013;1:12\u20133.","journal-title":"Ann Transl Med"},{"key":"293_CR76","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/S1470-2045(12)70475-8","volume":"13","author":"JC Mathers","year":"2012","unstructured":"Mathers JC, Movahedi M, Macrae F, et al. Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet Oncol. 2012;13:1242\u20139.","journal-title":"Lancet Oncol"},{"key":"293_CR77","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/S0140-6736(11)61720-0","volume":"379","author":"PM Rothwell","year":"2012","unstructured":"Rothwell PM, Price JF, Fowkes FGR, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379:1602\u201312. This study analyzes the results of 51 randomized, controlled trials of aspirin.","journal-title":"Lancet"},{"key":"293_CR78","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ahj.2011.04.006","volume":"162","author":"JS Berger","year":"2011","unstructured":"Berger JS, Lala A, Krantz MJ, et al. Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: a meta-analysis of randomized trials. Am Heart J. 2011;162:115\u2013124.e2.","journal-title":"Am Heart J"},{"key":"293_CR79","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00439-011-1028-3","volume":"130","author":"K Offit","year":"2011","unstructured":"Offit K. Personalized medicine: new genomics, old lessons. Hum Genet. 2011;130:3\u201314. This paper by a world-renowned hereditary cancer researcher provides an excellent, thought-provoking look at personalized medicine in relation to genomics.","journal-title":"Hum Genet"},{"key":"293_CR80","first-page":"768","volume":"11","author":"V Morris","year":"2013","unstructured":"Morris V, Kopetz S. Clinical biomarkers in colorectal cancer. Clin Adv Hematol Oncol. 2013;11:768\u201376. This gives an up-to-date overview of the clinical use of biomarkers in colorectal cancer. Emphasis is given to the use of biomarkers in targeted chemotherapy.","journal-title":"Clin Adv Hematol Oncol"},{"key":"293_CR81","first-page":"939","volume":"150","author":"TT Wu","year":"1997","unstructured":"Wu TT, Rezai B, Rashid A, et al. Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. Am J Pathol. 1997;150:939\u201347.","journal-title":"Am J Pathol"},{"key":"293_CR82","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/BF02303487","volume":"5","author":"JR Howe","year":"1998","unstructured":"Howe JR, Mitros FA, Summers RW. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol. 1998;5:751\u20136.","journal-title":"Ann Surg Oncol"},{"key":"293_CR83","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1056\/NEJM198706113162404","volume":"316","author":"FM Giardiello","year":"1987","unstructured":"Giardiello FM, Welsh SB, Hamilton SR, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med. 1987;316:1511\u20134.","journal-title":"N Engl J Med"}],"container-title":["Current Treatment Options in Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-014-0293-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11864-014-0293-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-014-0293-5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T19:34:28Z","timestamp":1559417668000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11864-014-0293-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,15]]},"references-count":83,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["293"],"URL":"https:\/\/doi.org\/10.1007\/s11864-014-0293-5","relation":{},"ISSN":["1527-2729","1534-6277"],"issn-type":[{"value":"1527-2729","type":"print"},{"value":"1534-6277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,15]]}}}