{"corpus_id":23612953,"paper_sha":"298ed55a76a6da9c8e5a368b22eee9895adedcc2","doi":"10.1053/GAST.2001.27996","arxiv_id":null,"pmid":11606497,"pmcid":null,"mag_id":2117618517,"dblp_id":null,"acl_id":null,"title":"The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer.","year":2001,"publication_date":"2001-10-01","venue":"Gastroenterology","journal":{"name":"Gastroenterology","pages":"\n          830-8\n        ","volume":"121 4"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't","Research Support, U.S. Gov't, P.H.S."],"s2_fields_of_study":["Biology","Medicine"],"reference_count":46,"citation_count":270,"influential_citation_count":9,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adaptor Proteins, Signal Transducing","mj":false,"ui":"D048868"},{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Amino Acid Substitution","mj":false,"ui":"D019943"},{"d":"Base Pair Mismatch","mj":false,"ui":"D020137"},{"d":"California","mj":false,"qs":[{"q":"epidemiology","mj":false,"ui":"Q000453"}],"ui":"D002140"},{"d":"Carrier Proteins","mj":false,"ui":"D002352"},{"d":"Colorectal Neoplasms, Hereditary Nonpolyposis","mj":false,"qs":[{"q":"epidemiology","mj":true,"ui":"Q000453"},{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D003123"},{"d":"DNA Repair","mj":false,"ui":"D004260"},{"d":"DNA-Binding Proteins","mj":true,"ui":"D004268"},{"d":"Exons","mj":false,"ui":"D005091"},{"d":"Family","mj":false,"ui":"D005190"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Microsatellite Repeats","mj":false,"ui":"D018895"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"MutL Protein Homolog 1","mj":false,"ui":"D000070957"},{"d":"MutS Homolog 2 Protein","mj":false,"ui":"D051718"},{"d":"Mutation","mj":false,"ui":"D009154"},{"d":"Mutation, Missense","mj":false,"ui":"D020125"},{"d":"Neoplasm Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D009363"},{"d":"Nuclear Proteins","mj":false,"ui":"D009687"},{"d":"Proto-Oncogene Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D011518"},{"d":"Sweden","mj":false,"qs":[{"q":"epidemiology","mj":false,"ui":"Q000453"}],"ui":"D013548"},{"d":"Utah","mj":false,"qs":[{"q":"epidemiology","mj":false,"ui":"Q000453"}],"ui":"D014589"}],"chemicals":[{"n":"Adaptor Proteins, Signal Transducing","ui":"D048868","reg":"0"},{"n":"Carrier Proteins","ui":"D002352","reg":"0"},{"n":"DNA-Binding Proteins","ui":"D004268","reg":"0"},{"n":"MLH1 protein, human","ui":"C501486","reg":"0"},{"n":"Neoplasm Proteins","ui":"D009363","reg":"0"},{"n":"Nuclear Proteins","ui":"D009687","reg":"0"},{"n":"Proto-Oncogene Proteins","ui":"D011518","reg":"0"},{"n":"MSH2 protein, human","ui":"C497172","reg":"EC 3.6.1.3"},{"n":"MutL Protein Homolog 1","ui":"D000070957","reg":"EC 3.6.1.3"},{"n":"MutS Homolog 2 Protein","ui":"D051718","reg":"EC 3.6.1.3"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.gastrojournal.org/article/S0016508501914593/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/298ed55a76a6da9c8e5a368b22eee9895adedcc2","s2_open_access_license":"CCBY","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"BACKGROUND & AIMS\nEstimates of the frequency of hereditary nonpolyposis colon cancer (HNPCC) based on clinical criteria have varied widely. Recent studies of germline mismatch repair gene mutations have suggested that HNPCC accounts for close to 3% of all colon cancer, but this estimate may have been inflated by inclusion of founder effects peculiar to Finland. We therefore determined by genetic criteria the colon cancer burden associated with HNPCC in a population-based study of 1066 individuals from Utah and California.\n\n\nMETHODS\nThe coding regions of mismatch repair genes hMSH2 and hMLH1 were sequenced from the germline of those individuals whose tumors exhibited microsatellite instability.\n\n\nRESULTS\nMicrosatellite instability was present in 16% (171/1066) of tumors. Pathogenic germline mismatch repair gene mutations were identified in 7 individuals, and missense amino acid changes of uncertain significance were identified in another 6 individuals. After adjusting for the availability of sufficient germline DNA for sequencing, the 7 clearly pathogenic mutations accounted for 0.86% of colon cancer at the population level. Individuals with these mutations were significantly younger, more likely to have a family history of colon and endometrial cancer, and more likely to have first-degree relatives with a young-age onset of colon cancer than individuals with unstable tumors but without germline mutations (P < 0.01).\n\n\nCONCLUSIONS\nWe conclude that genetically defined HNPCC accounts for a very small percentage of colon cancer at the population level, a percentage less than that estimated by most previous clinical studies.","claims":[{"public_id":"cl_7335c10f483dd63ac40fa3ab79bba25b","status":"active","text":"After adjusting for availability of germline DNA, seven pathogenic germline mismatch repair gene mutations accounted for 0.86% of colon cancer at the population level.","confidence":0.97,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_7335c10f483dd63ac40fa3ab79bba25b"},{"public_id":"cl_3b8335a58ed83bd2151ed9afa2911247","status":"active","text":"Genetically defined hereditary nonpolyposis colon cancer accounts for a very small percentage of colon cancer at the population level, lower than estimates from most previous clinical studies, and previous estimates may have been inflated by founder effects peculiar to Finland.","confidence":0.95,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_3b8335a58ed83bd2151ed9afa2911247"},{"public_id":"cl_603c2ed3b08aa90b3253a910509fda8a","status":"active","text":"Individuals with pathogenic germline mutations were significantly younger, more likely to have a family history of colon and endometrial cancer, and more likely to have first-degree relatives with young-age onset of colon cancer compared with individuals whose tumors were microsatellite-unstable but lacked germline mutations (P < 0.01).","confidence":0.96,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_603c2ed3b08aa90b3253a910509fda8a"},{"public_id":"cl_e667a6dff26a76d77fa8d3e1de4db59b","status":"active","text":"Microsatellite instability was present in 16% (171/1066) of tumors in a population-based cohort from Utah and California.","confidence":0.98,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ 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