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UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients

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Abstract

Background

Gene polymorphisms of the UDP-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) contribute to individual variations in adverse events among patients administered irinotecan, and the distribution of the polymorphisms shows large interethnic differences. Variation in the solute carrier organic anion-transporter family, member 1B1 (SLCO1B1) gene also has a significant effect on the disposition of irinotecan in Asian cancer patients. In the present study, we evaluated the association of genetic polymorphisms of UGT1A1 and SLCO1B1 with irinotecanrelated neutropenia in Japanese cancer patients.

Methods

One hundred and thirty-five consecutive patients treated with irinotecan were enrolled. Genotypes of UGT1A1 (*60, *28, *6, and *27) and SLCO1B1 (*1b, *5, and haplotype *15) were determined by direct sequencing. Severe neutropenia refers to events observed during the first cycle of irinotecan treatment.

Results

Severe neutropenia was observed in 29 patients (22%). Six patients were homozygous and 48 heterozygous for UGT1A1*6. Only 1 patient was homozygous for UGT1A1*28. Homozygosity for UGT1A1*6 was associated with a high risk of severe neutropenia (odds ratio [OR], 7.78; 95% confidence interval [CI], 1.36 to 44.51). No significant association was found between severe neutropenia and other UGT1A1 polymorphisms or SLCO1B1 polymorphisms.

Conclusion

These findings suggest that the UGT1A1*6 polymorphism is a potential predictor of severe neutropenia caused by irinotecan in Japanese cancer patients.

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Authors and Affiliations

  1. Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masahide Onoue, Tomohiro Terada, Masahiko Kobayashi, Toshiya Katsura & Ken-ichi Inui

  2. Outpatient Oncology Unit, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan

    Shigemi Matsumoto, Kazuhiro Yanagihara, Takafumi Nishimura & Masashi Kanai

  3. Department of Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan

    Satoshi Teramukai & Masanori Fukushima

  4. Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan

    Akira Shimizu

Authors
  1. Masahide Onoue
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  2. Tomohiro Terada
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  3. Masahiko Kobayashi
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  4. Toshiya Katsura
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  5. Shigemi Matsumoto
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  6. Kazuhiro Yanagihara
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  7. Takafumi Nishimura
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  8. Masashi Kanai
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  9. Satoshi Teramukai
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  10. Akira Shimizu
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  11. Masanori Fukushima
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  12. Ken-ichi Inui
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Corresponding author

Correspondence to Ken-ichi Inui.

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Onoue, M., Terada, T., Kobayashi, M. et al. UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients. Int J Clin Oncol 14, 136–142 (2009). https://doi.org/10.1007/s10147-008-0821-z

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  • DOI: https://doi.org/10.1007/s10147-008-0821-z

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