Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer.
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.
Fujita
Ken-ichi
K
Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Yamane, Hidaka, Japan. fujitak@saitama-med.ac.jp
Ando
Yuichi
Y
Yamamoto
Wataru
W
Miya
Toshimichi
T
Endo
Hisashi
H
Sunakawa
Yu
Y
Araki
Kazuhiro
K
Kodama
Keiji
K
Nagashima
Fumio
F
Ichikawa
Wataru
W
Narabayashi
Masaru
M
Akiyama
Yuko
Y
Kawara
Kaori
K
Shiomi
Mari
M
Ogata
Hiroyasu
H
Iwasa
Hiroyasu
H
Okazaki
Yasushi
Y
Hirose
Takashi
T
Sasaki
Yasutsuna
Y
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
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