Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese
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.
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.
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).
ABCB1 1236 TT genotype and older age might be a predictor of PIPN, which diminishes quality of life of cancer survivors.
KeywordsPaclitaxel-induced peripheral neuropathy Older age SLCO1B3 CYP2C8 ABCB1
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.
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.
- 9.Seidman AD, Berry D, Cirrincione C et al (2008) Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 26:1642–1649CrossRefPubMedGoogle Scholar