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Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer

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Abstract

Purpose

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.

Conclusion

Our findings suggest that pharmacogenetics can be used to predict the risk of morphine-induced adverse events.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research (C) (19590542) from the Japan Society for the Promotion of Science to K.F., a grant from the Japan Research Foundation for Clinical Pharmacology to K.F., Grant-in-Aid for Development of New Technology from The Promotion to Y.O. and Mutual Aid Corporation for Private Schools of Japan to Y.O. We thank A. Sparreboom (St. Jude Children’s Research Hospital) for kind review of our manuscript, Y. Yatsuka and T. Hirata for their technical assistance.

Conflict of interest statement

None.

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Authors and Affiliations

  1. Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan

    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, Takashi Hirose & Yasutsuna Sasaki

  2. Project Research Laboratory, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1241, Japan

    Ken-ichi Fujita, Fumio Nagashima, Yuko Akiyama & Yasutsuna Sasaki

  3. Department of Biopharmaceutics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan

    Mari Shiomi & Hiroyasu Ogata

  4. Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1241, Japan

    Hiroyasu Iwasa & Yasushi Okazaki

Authors
  1. Ken-ichi Fujita
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  2. Yuichi Ando
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  3. Wataru Yamamoto
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  18. Takashi Hirose
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  19. Yasutsuna Sasaki
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Corresponding author

Correspondence to Ken-ichi Fujita.

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Fujita, Ki., Ando, Y., Yamamoto, W. et al. Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer. Cancer Chemother Pharmacol 65, 251–258 (2010). https://doi.org/10.1007/s00280-009-1029-2

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  • DOI: https://doi.org/10.1007/s00280-009-1029-2

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