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Cancer Chemotherapy and Pharmacology

, Volume 79, Issue 6, pp 1179–1186 | Cite as

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

  • Yuko Tanabe
  • Chikako ShimizuEmail author
  • 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
Original Article

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.

Keywords

Paclitaxel-induced peripheral neuropathy Older age SLCO1B3 CYP2C8 ABCB1 

Notes

Acknowledgements

This work was supported by a Scientific Research Grant of the Ministry of Health, Labor, and Welfare (H21-021), and the National Cancer Center Research and Development Fund (23-A-30, 26-A-20). We thank Ms. Masayo Kawamura, Ms. Nao Nakamura, Ms. Kiyomi Nonogaki, and Ms. Hitomi Sato for helping with the data collection.

Compliance with ethical standards

Conflict of interest

YF reports grants from Taiho Pharmaceutical Co. Ltd, grants from Takeda Pharmaceutical Company Ltd, grants from Takeda Bio Development Center Ltd, grants and other from Chugai Pharmaceutical Co Ltd, other from Astra Zeneca KK, other from Eisai Co Ltd, other from Daiichi Sankyo Co Ltd, other from Sanofi-Aventis KK, grants and other from Eli Lilly Japan KK, other from Yakult Honsha Co Ltd, other from NEC Corporation, outside the submitted work. CS reports grants from Eli Lilly Japan KK and Pfizer KK. KH is currently an employee at Chugai Pharmaceutical Europe. The other authors have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki.

Supplementary material

280_2017_3314_MOESM1_ESM.docx (30 kb)
Supplementary material 1 (DOCX 30 kb)
280_2017_3314_MOESM2_ESM.pdf (30 kb)
Supplementary material 2 (PDF 29 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Yuko Tanabe
    • 1
    • 2
    • 3
  • Chikako Shimizu
    • 2
    Email author
  • Akinobu Hamada
    • 3
    • 4
  • Kenji Hashimoto
    • 2
  • Kazutaka Ikeda
    • 5
  • Daisuke Nishizawa
    • 5
  • Junko Hasegawa
    • 5
  • Akihiko Shimomura
    • 2
    • 6
  • Yukinori Ozaki
    • 6
  • Nobuko Tamura
    • 7
  • Harukaze Yamamoto
    • 2
  • Mayu Yunokawa
    • 2
  • Kan Yonemori
    • 2
  • Toshimi Takano
    • 6
  • Hidetaka Kawabata
    • 7
  • Kenji Tamura
    • 1
    • 2
    • 3
  • Yasuhiro Fujiwara
    • 2
  1. 1.Department of Experimental TherapeuticsNational Cancer Center HospitalTokyoJapan
  2. 2.Department of Breast and Medical OncologyNational Cancer Center HospitalTokyoJapan
  3. 3.Department of Medical Oncology and Translational Research, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
  4. 4.Division of Clinical Pharmacology and Translational Research, Exploratory Oncology Research and Clinical Trial CenterNational Cancer CenterTokyoJapan
  5. 5.Addictive Substance ProjectTokyo Metropolitan Institute of Medical ScienceTokyoJapan
  6. 6.Department of Medical OncologyToranomon HospitalTokyoJapan
  7. 7.Department of Breast and Endocrine SurgeryToranomon HospitalTokyoJapan

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