title: [Examination of UGT1A1 polymorphisms and irinotecan-induced neutropenia in patients with Colorectal cancer].
abstract: Irinotecan is an effective drug in the treatment of colorectal cancer. However, there are reports of an association between certain UGT1A1 genetic polymorphisms and the development of adverse reactions(such as neutropenia)related to irinotecan metabolism. We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic polymorphisms in these patients yielded the following classifications: a wild-type group( *1/*1)comprising 13 patients(52%), a heterozygous group(*1/ *28, *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2 patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group, 30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4 neutropenia only occurred in the homozygous group. These results suggest that a dose reduction of irinotecan should be considered for patients who fall into the homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such patients might be susceptible to grade 4 neutropenia.
authors.affiliation: Dept. of Surgery, Tomishiro Central Hospital.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Teruya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakachi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Shimabukuro
authors.forename: Daisuke
authors.initials: D
authors.lastname: Toritsuka
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Azuma
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Hanashiro
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nishiki
authors.forename: Morihito
authors.initials: M
authors.lastname: Ota
authors.forename: Masamori
authors.initials: M
authors.lastname: Shimabuku
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiroma
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D007970:Leukopenia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme