{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:30:17Z","timestamp":1788856217282,"version":"build-2803163510"},"reference-count":19,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,9]]},"abstract":"<jats:p>\n                    Classical familial adenomatous polyposis (FAP) is a high-penetrance autosomal dominant disease that predisposes to hundreds or thousands of colorectal adenomas and carcinoma and that results from truncating mutations in the\n                    <jats:italic>APC<\/jats:italic>\n                    gene. A variant of FAP is attenuated adenomatous polyposis coli, which results from germ-line mutations in the 5\u2032 and 3\u2032 regions of the\n                    <jats:italic>APC<\/jats:italic>\n                    gene. Attenuated adenomatous polyposis coli patients have \u201cmultiple\u201d colorectal adenomas (typically fewer than 100) without the florid phenotype of classical FAP. Another group of patients with multiple adenomas has no mutations in the\n                    <jats:italic>APC<\/jats:italic>\n                    gene, and their phenotype probably results from variation at a locus, or loci, elsewhere in the genome. Recently, however, a missense variant of\n                    <jats:italic>APC<\/jats:italic>\n                    (I1307K) was described that confers an increased risk of colorectal tumors, including multiple adenomas, in Ashkenazim. We have studied a set of 164 patients with multiple colorectal adenomas and\/or carcinoma and analyzed codons 1263\u20131377 (exon 15G) of the\n                    <jats:italic>APC<\/jats:italic>\n                    gene for germ-line variants. Three patients with the I1307K allele were detected, each of Ashkenazi descent. Four patients had a germ-line E1317Q missense variant of\n                    <jats:italic>APC<\/jats:italic>\n                    that was not present in controls; one of these individuals had an unusually large number of metaplastic polyps of the colorectum. There is increasing evidence that there exist germ-line variants of the\n                    <jats:italic>APC<\/jats:italic>\n                    gene that predispose to the development of multiple colorectal adenomas and carcinoma, but without the florid phenotype of classical FAP, and possibly with importance for colorectal cancer risk in the general population.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.18.10722","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"10722-10727","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":161,"title":["The\n                    <i>APC<\/i>\n                    variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history"],"prefix":"10.1073","volume":"95","author":[{"given":"Ian M.","family":"Frayling","sequence":"first","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas E.","family":"Beck","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Ilyas","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis","family":"Dove-Edwin","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Goodman","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Pack","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Bell","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Williams","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley V.","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw J. W.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"Talbot","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter F.","family":"Bodmer","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P. M.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Imperial Cancer Research Fund, Kennedy\u2013Galton Centre for Medical Genetics, Wolfson Unit for Endoscopy, St. Mark\u2019s and Northwick Park Hospitals National Health Service Trust, Harrow, HA1 3UJ, United Kingdom; Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; Department of Clinical Genetics, Guy\u2019s Hospital, St. Thomas\u2019s Street, London, SE1 9RT, United Kingdom; and Tumor..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.1.121"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/1.4.229"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90538-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02281864"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050293"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.41.2.235"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-79"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1385\/0-89603-346-5:63","volume-title":"Molecular Diagnosis of Genetic Diseases","author":"Frayling I M","year":"1996","unstructured":"I M Frayling, A J Rowan Molecular Diagnosis of Genetic Diseases, ed R Elles (Totowa, New York), pp. 63\u201398 (1996)."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1997)10:5<376::AID-HUMU7>3.0.CO;2-D"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.7.2503"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.20.5804"},{"key":"e_1_3_3_12_2","first-page":"286","volume":"52","author":"Spirio L","year":"1993","unstructured":"L Spirio, L Nelson, K Ward, R Burt, R White, M Leppert Am J Hum Genet 52, 286\u2013296 (1993).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_13_2","first-page":"5805","volume":"19","author":"van Leeuwen C","year":"1991","unstructured":"C van Leeuwen, C Tops, C Breukel, H van der Klift, R Fodde, P M Khan Nucleic Acids Res 19, 5805 (1991).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380020602"},{"key":"e_1_3_3_15_2","first-page":"5480","volume":"57","author":"Petrukhin L","year":"1997","unstructured":"L Petrukhin, J E Dangel, L Vanderveer, J Costalas, A Bellacosa, G Grana, M Daly, A K Godwin Cancer Res 57, 5480\u20135484 (1997).","journal-title":"Cancer Res"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199602)15:2<122::AID-GCC7>3.0.CO;2-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19930201)71:3<672::AID-CNCR2820710304>3.0.CO;2-H"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/00313029700169494"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)89159-3"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.18.10722","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:03:51Z","timestamp":1649869431000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.18.10722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,9]]},"references-count":19,"journal-issue":{"issue":"18","published-print":{"date-parts":[[1998,9]]}},"alternative-id":["10.1073\/pnas.95.18.10722"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.18.10722","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,9]]},"assertion":[{"value":"1998-07-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}