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An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel

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Abstract

Purpose

Docetaxel is one of the most widely used chemotherapy drugs for gynecological cancers. A dose-limiting factor of docetaxel is severe neutropenia, and previous reports showed that grade 4 neutropenia was observed in approximately 70 % of Japanese patients treated with docetaxel. In order to elucidate a valid biomarker for docetaxel-induced neutropenia, we analyzed 42 Japanese patients with gynecological cancers such as ovarian cancer and endometrial cancer of the uterus.

Methods

As a first step, AUC of docetaxel was examined in 10 patients and 1,936 SNPs of 225 genes were genotyped using DMET Plus™ genotyping systems.

Results

The first screening revealed that 28 SNPs were associated with the AUC (P < 0.05), and we analyzed the associations between the 28 SNPs and neutrophil counts in the other 32 patients, with the result that CYP39A1 (rs7761731) was found to be the only SNP significantly associated (P = 0.049 OR = 9.0) with the incidence of grade 4 neutropenia among 28 SNPs.

Conclusions

This SNP in CYP39A1 may be a useful biomarker for predicting the risk of docetaxel-induced neutropenia.

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Acknowledgments

We are indebted to Takako Aoki and Junko Oka for their excellent technical assistance. This work was supported by the Global COE program, Multidisciplinary Education and Research Center for Regenerative Medicine (MERCREM), from the Ministry of Education, Culture, Sports Science, and Technology (MEXT), Japan.

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Authors and Affiliations

  1. Affiliated Field of Medical Genetics, Division of Biomedical Engineering and Science, Graduate Course of Medicine, Graduate School of Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Toshitaka Uchiyama, Hitoshi Kanno, Naoyuki Kamatani & Kayoko Saito

  2. Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, Japan

    Hitoshi Kanno & Kayoko Saito

  3. Department of Transfusion Medicine and Cell Processing, Tokyo Women’s Medical University, Tokyo, Japan

    Hitoshi Kanno & Hisaichi Fujii

  4. Department of Obstetrics and Gynecology, Tokyo Women’s Medical University, Tokyo, Japan

    Ken Ishitani & Hideo Matsui

  5. Department of Obstetrics and Gynecology, Sanno Medical Center, International University of Health and Welfare, Tokyo, Japan

    Hiroaki Ohta

  6. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Kanagawa, Japan

    Naoyuki Kamatani

Authors
  1. Toshitaka Uchiyama
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  2. Hitoshi Kanno
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  3. Ken Ishitani
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  4. Hisaichi Fujii
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  5. Hiroaki Ohta
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  6. Hideo Matsui
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  7. Naoyuki Kamatani
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  8. Kayoko Saito
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Correspondence to Hitoshi Kanno.

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Uchiyama, T., Kanno, H., Ishitani, K. et al. An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel. Cancer Chemother Pharmacol 69, 1617–1624 (2012). https://doi.org/10.1007/s00280-012-1872-4

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  • DOI: https://doi.org/10.1007/s00280-012-1872-4

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