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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2017

01-06-2017 | Original Article

Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese

Authors: Yuko Tanabe, Chikako Shimizu, Akinobu Hamada, Kenji Hashimoto, Kazutaka Ikeda, Daisuke Nishizawa, Junko Hasegawa, Akihiko Shimomura, Yukinori Ozaki, Nobuko Tamura, Harukaze Yamamoto, Mayu Yunokawa, Kan Yonemori, Toshimi Takano, Hidetaka Kawabata, Kenji Tamura, Yasuhiro Fujiwara

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2017

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Abstract

Purpose

Whether age and inter-individual variability of pharmacogenetics are risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive. This study was conducted to evaluate the influence of previously investigated single nucleotide polymorphisms (SNPs) and age, using genotype data from a prospective study of paclitaxel-related toxicity in Japanese patients with breast cancer.

Methods

Peripheral blood mononuclear cells from 127 Japanese women with breast cancer who received weekly adjuvant paclitaxel were used to genotypes SLCO1B3 T334G (rs4149117), CYP2C8 A1196G (rs10509681), ABCB1 C1236T (rs1128503), ABCB1 G2677T/A (rs2032582), and ABCB1 C3435T (rs1045642). Genotypic and clinical factors were investigated for associations with PIPN.

Results

Of the five SNPs evaluated, no SNPs were significantly associated with grade 2 or higher PIPN. However, ABCB1 1236 TT showed a trend to associate with grade 2 or higher PIPN compared to ABCB1 CT/CC (odds ratio 2.1, 95% CI 0.991–4.548, p = 0.051). In subgroup analysis, patients ≥60 years old with an ABCB1 1236 TT had a higher incidence of ≥grade 2 PIPN compared to patients with CT or CC genotype (p = 0.027). On multivariable analysis, age ≥60 years and the ABCB1 1236 TT showed a significant association with ≥grade 2 PIPN (p = 0.005 and p = 0.034, respectively).

Conclusions

ABCB1 1236 TT genotype and older age might be a predictor of PIPN, which diminishes quality of life of cancer survivors.
Appendix
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Metadata
Title
Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese
Authors
Yuko Tanabe
Chikako Shimizu
Akinobu Hamada
Kenji Hashimoto
Kazutaka Ikeda
Daisuke Nishizawa
Junko Hasegawa
Akihiko Shimomura
Yukinori Ozaki
Nobuko Tamura
Harukaze Yamamoto
Mayu Yunokawa
Kan Yonemori
Toshimi Takano
Hidetaka Kawabata
Kenji Tamura
Yasuhiro Fujiwara
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3314-9

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