Yuko Tanabe1,2,3, Chikako Shimizu4, Akinobu Hamada3,5, Kenji Hashimoto2, Kazutaka Ikeda6, Daisuke Nishizawa6, Junko Hasegawa6, Akihiko Shimomura2,7, Yukinori Ozaki7, Nobuko Tamura8, Harukaze Yamamoto2, Mayu Yunokawa2, Kan Yonemori2, Toshimi Takano7, Hidetaka Kawabata8, Kenji Tamura1,2,3, Yasuhiro Fujiwara2. 1. Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 2. Department of Breast and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 3. Department of Medical Oncology and Translational Research, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan. 4. Department of Breast and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. cshimizu@ncc.go.jp. 5. Division of Clinical Pharmacology and Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 6. Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. 7. Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. 8. Department of Breast and Endocrine Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
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.
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 SLCO1B3T334G (rs4149117), CYP2C8 A1196G (rs10509681), ABCB1C1236T (rs1128503), ABCB1G2677T/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.
Authors: Shuiying Hu; Kevin M Huang; Elizabeth J Adams; Charles L Loprinzi; Maryam B Lustberg Journal: Clin Cancer Res Date: 2019-05-23 Impact factor: 12.531
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Authors: Alberto Guijosa; Ana Freyria; Jose Rodrigo Espinosa-Fernandez; Francisco J Estrada-Mena; Ana Sofía Armenta-Quiroga; Maria Fernanda Ortega-Treviño; Rodrigo Catalán; Bani Antonio-Aguirre; Cynthia Villarreal-Garza; Andric C Perez-Ortiz Journal: Clin Transl Sci Date: 2022-08-17 Impact factor: 4.438