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- Title
Genetic linkage of UGT1A7 and UGT1A9 polymorphisms to UGT1A1*6 is associated with reduced activity for SN-38 in Japanese patients with cancer.
- Authors
Fujita, Ken-ichi; Ando, Yuichi; Nagashima, Fumio; Yamamoto, Wataru; Eodo, Hisashi; Araki, Kazuhiro; Kodama, Keiji; Miya, Toshimichi; Narabayashi, Masaru; Sasaki, Yasutsuna
- Abstract
The phenotypic effects of UGT1A7 and UGT1A9 genetic polymorphisms on the in vivo pharmacokinetics of irinotecan were examined. Eighty-four Japanese patients with cancer who received irinotecan-based chemotherapy were enrolled. Polymorphisms present in UGT1A7 ( T to G transversion at −57 and UGT1A7*2 to *9), UGT1A9 (9 or 10 repeat of T at −118 [−118( T)9 or 10] and UGT1A9*2 to *5), and UGT1A1 ( UGT1A1*6, UGT1A1*27, and UGT1A1*28) were analyzed for all patients. Pharmacokinetics of irinotecan were examined in 52 patients. The most frequent haplotype (haplotype I, 56.7%, 95% CI 53.1–60.4) consisted of polymorphisms related to normal catalytic or transcriptional activity [ T at −57 and *1 of UGT1A7, −118( T)10 of UGT1A9, and UGT1A1*1]. The second most frequent haplotype (haplotype II, 15.0%, 95% CI 12.4–18.3) consisted of polymorphisms related to reduced catalytic or transcriptional activity [−57 T > G and *3 of UGT1A7 and −118( T)9 of UGT1A9 linked to UGT1A1*6]. The AUCSN-38/AUCSN-38G ratios in three patients homozygous for haplotype II were significantly higher than those in 20 patients with I/I diplotype ( P = 0.011). Neither of these patients had UGT1A1*28. Genetic linkage of UGT1A7 and UGT1A9 polymorphisms to UGT1A1*6, related to reduced catalytic and transcriptional activities of UGTs, is associated with the decreased glucuronosyltransferase activity for SN-38 in Japanese patients with cancer.
- Subjects
GENETIC polymorphisms; POPULATION genetics; GENETICS; CANCER patients; JAPANESE people; DISEASES
- Publication
Cancer Chemotherapy & Pharmacology, 2007, Vol 60, Issue 4, p515
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-006-0396-1