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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2012

01-06-2012 | Original Article

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

Authors: Toshitaka Uchiyama, Hitoshi Kanno, Ken Ishitani, Hisaichi Fujii, Hiroaki Ohta, Hideo Matsui, Naoyuki Kamatani, Kayoko Saito

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2012

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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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Metadata
Title
An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel
Authors
Toshitaka Uchiyama
Hitoshi Kanno
Ken Ishitani
Hisaichi Fujii
Hiroaki Ohta
Hideo Matsui
Naoyuki Kamatani
Kayoko Saito
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-012-1872-4

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