{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:30:28Z","timestamp":1782808228598,"version":"3.54.5"},"reference-count":17,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"published-print":{"date-parts":[[2005,5]]},"abstract":"\n Combination cancer chemotherapy induced toxicity can be associated with combined pharmacogenetic syndromes. Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme involved in the catabolic detoxification of 5-fluorouracil (5FU). A heterozygous G > A transition at the 5\u2032 splicing donor consensus sequence in intron 14 leading to exon 14 skipping (IVS14+1 G > A, DPYD*2A) with partial loss of enzyme activity may be partly responsible for 5FU induced toxicity, whereas irinotecan associated toxicity may in part be explained by an aberrant UGT1A1 promoter (TA)\n n<\/jats:sub>\n genotype underlying Gilbert\u2019s syndrome with reduced liver glucuronidation activity. This report describes a 44 year old white woman who suffered from severe gastrointestinal and haematological toxicity while undergoing 5FU\n 24h<\/jats:sub>\n \/folinic acid\/irinotecan treatment for adenocarcinoma of the sigmoid colon. Despite appropriate supportive treatment, her condition rapidly deteriorated and led to death. Molecular analysis revealed a hitherto undescribed combined pharmacogenetic syndrome, consisting of heterozygosity for the DPD IVS14+1 G > A mutation and UGT1A1 (TA)\n 6\/7<\/jats:sub>\n heterozygosity, which probably contributed to the fatal outcome in this patient.\n <\/jats:p>","DOI":"10.1136\/jcp.2004.022319","type":"journal-article","created":{"date-parts":[[2005,4,27]],"date-time":"2005-04-27T16:16:29Z","timestamp":1114618589000},"page":"553-555","source":"Crossref","is-referenced-by-count":21,"title":["5-Fluorouracil\/irinotecan induced lethal toxicity as a result of a combined pharmacogenetic syndrome: report of a case"],"prefix":"10.1136","volume":"58","author":[{"given":"M","family":"Steiner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Seule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Freund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C H","family":"K\u00f6hne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Schuff-Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2005,4,27]]},"reference":[{"key":"2025121408122146000_58.5.553.1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1056\/NEJM198507253130407","volume":"313","year":"1985","journal-title":"N Engl J Med"},{"key":"2025121408122146000_58.5.553.2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.ejca.2003.12.004","volume":"40","year":"2004","journal-title":"Eur J Cancer"},{"key":"2025121408122146000_58.5.553.3","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1172\/JCI118830","volume":"98","year":"1996","journal-title":"J Clin Invest"},{"key":"2025121408122146000_58.5.553.4","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5379"},{"key":"2025121408122146000_58.5.553.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(01)00188-6"},{"key":"2025121408122146000_58.5.553.6","first-page":"2832","volume":"7","year":"2001","journal-title":"Clin Cancer Res"},{"key":"2025121408122146000_58.5.553.7","first-page":"1149","volume":"7","year":"2001","journal-title":"Clin Cancer Res"},{"key":"2025121408122146000_58.5.553.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02034-1"},{"key":"2025121408122146000_58.5.553.9","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008261821434"},{"key":"2025121408122146000_58.5.553.10","first-page":"6921","volume":"60","year":"2000","journal-title":"Cancer Res"},{"key":"2025121408122146000_58.5.553.11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.07.173"},{"key":"2025121408122146000_58.5.553.12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/clinchem\/46.2.309","volume":"46","year":"2000","journal-title":"Clin Chem"},{"key":"2025121408122146000_58.5.553.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8170"},{"key":"2025121408122146000_58.5.553.14","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200210000-00007"},{"key":"2025121408122146000_58.5.553.15","first-page":"596","volume":"29","year":"2001","journal-title":"Drug Metab Dispos"},{"key":"2025121408122146000_58.5.553.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)70078-0"},{"key":"2025121408122146000_58.5.553.17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.01.950"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp.2004.022319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T16:12:30Z","timestamp":1765728750000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp.2004.022319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,27]]},"references-count":17,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2005,4,27]]},"published-print":{"date-parts":[[2005,5]]}},"alternative-id":["10.1136\/jcp.2004.022319"],"URL":"https:\/\/doi.org\/10.1136\/jcp.2004.022319","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4,27]]}}}