{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:44:26Z","timestamp":1782744266096,"version":"3.54.5"},"reference-count":75,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This reviews the historical evolution of our understanding of the familial gastrointestinal cancer syndromes. It begins centuries ago with the appreciation of the gastrointestinal polyposis syndromes and the relationship between adenomatous polyps and cancer. However, it was not until 1991 that the\n                    <jats:italic>APC<\/jats:italic>\n                    gene was cloned and linked to familial adenomatous polyposis. Mutated oncogenes and inactivated tumor suppressor genes were discovered in the 1970s, and it was appreciated by the late 1980s that these genetic alterations occurred sequentially during the evolution of gastrointestinal tumors. During the exploration of this process, it was unexpectedly recognized in the early 1990s that hereditary non\u2010polyposis colorectal cancers had a specific mutational signature that was the result of inactivation of the DNA mismatch repair system. This disease involved a unique group of mutational targets, distinctive pathways to tumor development, and the remarkable recognition in the 21st century of novel and highly effective therapeutic approaches to tumor control. Mixed in with these discoveries was the appreciation of multiple unique hamartomatous polyposis syndromes. The progress made over the past 50\u2009years is remarkable and highlights the rapid evolution of new technologies and insightful research.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70606","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:49:44Z","timestamp":1782740984000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Milestones in Hereditary Colorectal Cancer Research"],"prefix":"10.1002","author":[{"given":"Clement Richard","family":"Boland","sequence":"first","affiliation":[{"name":"Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Yurgelun","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1001\/archinte.1913.00070050063006","article-title":"Heredity With Reference to Carcinoma as Shown by the Study of the Cases Examined in the Pathology Laboratory at the University of Michigan, 1895\u20101913","volume":"12","author":"Warthin A. S.","year":"1913","journal-title":"Archives of Internal Medicine"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s10689-013-9637-8","article-title":"The History of Lynch Syndrome","volume":"12","author":"Boland C. R.","year":"2013","journal-title":"Familial Cancer"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10689-004-4489-x","article-title":"Evolution of the Nomenclature for the Hereditary Colorectal Cancer Syndromes","volume":"4","author":"Boland C. 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M.","year":"2003","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of Mutational Processes in Human Cancer","volume":"500","author":"Alexandrov L. B.","year":"2013","journal-title":"Nature"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1126\/science.181.4100.665","article-title":"Murine C\u2010Type RNA Virus From Spontaneous Neoplasms: In\u00a0Vitro Host Range and Oncogenic Potential","volume":"181","author":"Peters R. L.","year":"1973","journal-title":"Science"},{"key":"e_1_2_12_18_1","first-page":"153","article-title":"Biochemical Mechanisms of Oncogene Activity: Proteins Encoded by Oncogenes. Introduction","volume":"5","author":"Varmus H.","year":"1986","journal-title":"Cancer Survivorship"},{"key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1073\/pnas.68.4.820","article-title":"Mutation and Cancer: Statistical Study of Retinoblastoma","volume":"68","author":"Knudson A. G.","year":"1971","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/327293a0","article-title":"Prevalence of Ras Gene Mutations in Human Colorectal Cancers","volume":"327","author":"Bos J. 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V.","year":"2013","journal-title":"Familial Cancer"},{"key":"e_1_2_12_41_1","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1053\/j.gastro.2009.12.064","article-title":"Microsatellite Instability in Colorectal Cancer","volume":"138","author":"Boland C. R.","year":"2010","journal-title":"Gastroenterology"},{"key":"e_1_2_12_42_1","first-page":"4308","article-title":"Human Chromosome 3 Corrects Mismatch Repair Deficiency and Microsatellite Instability and Reduces N\u2010Methyl\u2010N\u2032\u2010Nitro\u2010N\u2010Nitrosoguanidine Tolerance in Colon Tumor Cells With Homozygous hMLH1 Mutation","volume":"54","author":"Koi M.","year":"1994","journal-title":"Cancer Research"},{"key":"e_1_2_12_43_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1172\/JCI118767","article-title":"Competency in Mismatch Repair Prohibits Clonal Expansion of Cancer Cells Treated With N\u2010Methyl\u2010N\u2032\u2010Nitro\u2010N\u2010Nitrosoguanidine","volume":"98","author":"Carethers J. M.","year":"1996","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_12_44_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0016-5085(99)70558-5","article-title":"Mismatch Repair Proficiency and In\u00a0Vitro Response to 5\u2010Fluorouracil","volume":"117","author":"Carethers J. M.","year":"1999","journal-title":"Gastroenterology"},{"key":"e_1_2_12_45_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1053\/j.gastro.2003.12.023","article-title":"Use of 5\u2010Fluorouracil and Survival in Patients With Microsatellite\u2010Unstable Colorectal Cancer","volume":"126","author":"Carethers J. M.","year":"2004","journal-title":"Gastroenterology"},{"key":"e_1_2_12_46_1","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1053\/j.gastro.2008.01.015","article-title":"Immune Response Against Frameshift\u2010Induced Neopeptides in HNPCC Patients and Healthy HNPCC Mutation Carriers","volume":"134","author":"Schwitalle Y.","year":"2008","journal-title":"Gastroenterology"},{"key":"e_1_2_12_47_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/S1470-2045(12)70109-2","article-title":"Prevalence of Mismatch Repair\u2010Deficient Crypt Foci in Lynch Syndrome: A Pathological Study","volume":"13","author":"Kloor M.","year":"2012","journal-title":"Lancet Oncology"},{"key":"e_1_2_12_48_1","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/modpathol.2017.39","article-title":"Mismatch Repair Deficiency Commonly Precedes Adenoma Formation in Lynch Syndrome\u2010Associated Colorectal Tumorigenesis","volume":"30","author":"Sekine S.","year":"2017","journal-title":"Modern Pathology"},{"key":"e_1_2_12_49_1","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1158\/1940-6207.CAPR-11-0519","article-title":"Microsatellite Instability and DNA Mismatch Repair Protein Deficiency in Lynch Syndrome Colorectal Polyps","volume":"5","author":"Yurgelun M. B.","year":"2012","journal-title":"Cancer Prevention Research (Philadelphia, Pa.)"},{"key":"e_1_2_12_50_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/ijc.31300","article-title":"Three Molecular Pathways Model Colorectal Carcinogenesis in Lynch Syndrome","volume":"143","author":"Ahadova A.","year":"2018","journal-title":"International Journal of Cancer"},{"key":"e_1_2_12_51_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1008970","article-title":"Mathematical Modeling of Multiple Pathways in Colorectal Carcinogenesis Using Dynamical Systems With Kronecker Structure","volume":"17","author":"Haupt S.","year":"2021","journal-title":"PLoS Computational Biology"},{"key":"e_1_2_12_52_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/hmg\/ddi021","article-title":"Low Levels of Microsatellite Instability Characterize MLH1 and MSH2 HNPCC Carriers Before Tumor Diagnosis","volume":"14","author":"Alazzouzi H.","year":"2005","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_12_53_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1136\/gutjnl-2015-309675","article-title":"Cancer Incidence and Survival in Lynch Syndrome Patients Receiving Colonoscopic and Gynaecological Surveillance: First Report From the Prospective Lynch Syndrome Database","volume":"66","author":"Moller P.","year":"2017","journal-title":"Gut"},{"key":"e_1_2_12_54_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13053-023-00263-3","article-title":"Dominantly Inherited Micro\u2010Satellite Instable Cancer\u2014The Four Lynch Syndromes\u2014An EHTG, PLSD Position Statement","volume":"21","author":"Moller P.","year":"2023","journal-title":"Hereditary Cancer in Clinical Practice"},{"key":"e_1_2_12_55_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.gastro.2023.03.007","article-title":"A \u201cTwo\u2010In\u2010One Hit\u201d Model of Shortcut Carcinogenesis in MLH1 Lynch Syndrome Carriers","volume":"165","author":"Ahadova A.","year":"2023","journal-title":"Gastroenterology"},{"key":"e_1_2_12_56_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1136\/jitc-2021-004416","article-title":"Vaccines for Immunoprevention of DNA Mismatch Repair Deficient Cancers","volume":"10","author":"Hernandez\u2010Sanchez A.","year":"2022","journal-title":"Journal for Immunotherapy of Cancer"},{"key":"e_1_2_12_57_1","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1053\/j.gastro.2021.06.073","article-title":"Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model","volume":"161","author":"Gebert J.","year":"2021","journal-title":"Gastroenterology"},{"key":"e_1_2_12_58_1","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1158\/0008-5472.CAN-20-1072","article-title":"A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors With Microsatellite Instability","volume":"80","author":"Leoni G.","year":"2020","journal-title":"Cancer Research"},{"key":"e_1_2_12_59_1","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/S0140-6736(20)30366-4","article-title":"Cancer Prevention With Aspirin in Hereditary Colorectal Cancer (Lynch Syndrome), 10\u2010Year Follow\u2010Up and Registry\u2010Based 20\u2010Year Data in the CAPP2 Study: A Double\u2010Blind, Randomised, Placebo\u2010Controlled Trial","volume":"395","author":"Burn J.","year":"2020","journal-title":"Lancet"},{"key":"e_1_2_12_60_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccell.2015.03.001","article-title":"Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy","volume":"27","author":"Topalian S. L.","year":"2015","journal-title":"Cancer Cell"},{"key":"e_1_2_12_61_1","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD\u20101 Blockade in Tumors With Mismatch\u2010Repair Deficiency","volume":"372","author":"Le D. T.","year":"2015","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_12_62_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch Repair Deficiency Predicts Response of Solid Tumors to PD\u20101 Blockade","volume":"357","author":"Le D. 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M.","year":"2019","journal-title":"Nature"},{"key":"e_1_2_12_68_1","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1158\/2159-8290.CD-20-1508","article-title":"Werner Helicase Is a Synthetic\u2010Lethal Vulnerability in Mismatch Repair\u2010Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy","volume":"11","author":"Picco G.","year":"2021","journal-title":"Cancer Discovery"},{"key":"e_1_2_12_69_1","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1158\/2159-8290.CD-24-0052","article-title":"Novel WRN Helicase Inhibitors Selectively Target Microsatellite\u2010Unstable Cancer Cells","volume":"14","author":"Picco G.","year":"2024","journal-title":"Cancer Discovery"},{"key":"e_1_2_12_70_1","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1053\/j.gastro.2022.02.021","article-title":"Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi\u2010Society Task Force on Colorectal Cancer","volume":"162","author":"Boland C. 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