Cancer Chemother Pharmacol (2010) 65:251–258 DOI 10.1007/s00280-009-1029-2 123 ORIGINAL ARTICLE Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer Ken-ichi Fujita · Yuichi Ando · Wataru Yamamoto · Toshimichi Miya · Hisashi Endo · Yu Sunakawa · Kazuhiro Araki · Keiji Kodama · Fumio Nagashima · Wataru Ichikawa · Masaru Narabayashi · Yuko Akiyama · Kaori Kawara · Mari Shiomi · Hiroyasu Ogata · Hiroyasu Iwasa · Yasushi Okazaki · Takashi Hirose · Yasutsuna Sasaki Received: 23 January 2009 / Accepted: 4 May 2009 / Published online: 23 May 2009  Springer-Verlag 2009 Abstract Purpose To investigate the eVects of genetic polymor- phisms on morphine-induced adverse events in cancer patients. Methods We examined the relation of morphine-related adverse events to polymorphisms in UDP-glucuronosyl- transferase (UGT) 2B7, ATP-binding cassette, sub-family B, number 1 (ABCB1), and -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 signiWcantly 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 suVered from vomiting. Conclusion Our Wndings suggest that pharmacogenetics can be used to predict the risk of morphine-induced adverse events. Keywords Morphine · Cancer patients · Adverse reaction · Pharmacogenetics Introduction Severe pain caused by tumors is therapeutically managed by administration of opioid analgesics. Morphine is one of the most important and widely used opioids for cancer-pain relief, but large interindividual variability in its eVective- ness and adverse reactions are a major clinical disadvan- tage. Clinical pharmacology studies have demonstrated that wide interindividual variability in the response to a drug is associated with considerable pharmacokinetic or pharma- codynamic variability [1], which may be genetically deter- mined [2–4]. Morphine is predominantly glucuronidated by UDP- glucuronosyltransferase (UGT) 2B7 to form morphine 6-glucuronide (M6G) and morphine 3-glucuronide (M3G) [5]. M6G has clinically been shown to be a potent analge- sic, and the analgesic properties of morphine are enhanced K. Fujita (&) · Y. Ando · W. Yamamoto · T. Miya · H. Endo · Y. Sunakawa · K. Araki · K. Kodama · F. Nagashima · W. Ichikawa · M. Narabayashi · Y. Akiyama · K. Kawara · T. Hirose · Y. Sasaki Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan e-mail: fujitak@saitama-med.ac.jp K. Fujita · F. Nagashima · Y. Akiyama · Y. Sasaki Project Research Laboratory, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241, Japan M. Shiomi · H. Ogata Department of Biopharmaceutics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan H. Iwasa · Y. Okazaki Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241, Japan