title: Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer.
abstract: OBJECTIVE
  To investigate the effects of genetic polymorphisms on morphine-induced adverse events in cancer patients.
  
  
  METHODS
  We examined the relation of morphine-related adverse events to polymorphisms in UDP-glucuronosyltransferase (UGT) 2B7, ATP-binding cassette, sub-family B, number 1 (ABCB1), and μ-opioid receptor 1 genes in 32 Japanese cancer patients receiving oral controlled-release morphine sulfate tablets.
  
  
  RESULTS
  The T/T genotype at 1236 or TT/TT diplotype at 2677 and 3435 in ABCB1 was associated with significantly lower frequency of fatigue (grades 1-3) (P = 0.012 or 0.011, Fisher’s exact test). The UGT2B7*2 genotype was associated with the frequency of nausea (grades 1-3) (P = 0.023). The frequency of nausea was higher in patients without UGT2B7*2 allele than others. The diplotype at 2677 and 3435 in ABCB1 was associated with the frequency of vomiting (grades 1-3) (P = 0.011). No patient whose diplotype was consisted of no GC allele at 2677 and 3435 suffered from vomiting.
  
  
  CONCLUSIONS
  Our findings suggest that pharmacogenetics can be used to predict the risk of morphine-induced adverse events.
authors.affiliation: Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Yamane, Hidaka, Japan. fujitak@saitama-med.ac.jp
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
authors.forename: Wataru
authors.initials: W
authors.lastname: Yamamoto
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Miya
authors.forename: Hisashi
authors.initials: H
authors.lastname: Endo
authors.forename: Yu
authors.initials: Y
authors.lastname: Sunakawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Araki
authors.forename: Keiji
authors.initials: K
authors.lastname: Kodama
authors.forename: Fumio
authors.initials: F
authors.lastname: Nagashima
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Narabayashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Kaori
authors.initials: K
authors.lastname: Kawara
authors.forename: Mari
authors.initials: M
authors.lastname: Shiomi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogata
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iwasa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirose
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000493:pharmacokinetics; D044466:Asian People; D003692:Delayed-Action Preparations; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects* / Q000493:pharmacokinetics; D009369:Neoplasms / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy*; D011110:Polymorphism, Genetic; D017450:Receptors, Opioid, mu / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase