Tanabe Yuko, Shimizu Chikako, Hamada Akinobu, Hashimoto Kenji, Ikeda Kazutaka, Nishizawa Daisuke, Hasegawa Junko, Shimomura Akihiko, Ozaki Yukinori, Tamura Nobuko, Yamamoto Harukaze, Yunokawa Mayu, Yonemori Kan, Takano Toshimi, Kawabata Hidetaka, Tamura Kenji, Fujiwara Yasuhiro
Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Breast and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Cancer Chemother Pharmacol. 2017 Jun;79(6):1179-1186. doi: 10.1007/s00280-017-3314-9. Epub 2017 Apr 26.
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.
年龄和药物遗传学的个体间变异性是否为紫杉醇诱导的周围神经病变（PIPN）的危险因素尚无定论。本研究利用日本乳腺癌患者紫杉醇相关毒性前瞻性研究的基因型数据，评估先前研究的单核苷酸多态性（SNP）和年龄的影响。
收集127例接受每周辅助紫杉醇治疗的日本乳腺癌女性患者的外周血单个核细胞，对SLCO1B3 T334G（rs4149117）、CYP2C8 A1196G（rs10509681）、ABCB1 C1236T（rs1128503）、ABCB1 G2677T/A（rs2032582）和ABCB1 C3435T（rs1045642）进行基因分型。研究基因分型和临床因素与PIPN的相关性。
在评估的5个SNP中，没有SNP与2级或更高等级的PIPN显著相关。然而，与ABCB1 CT/CC相比，ABCB1 1236 TT显示出与2级或更高等级PIPN相关的趋势（比值比2.1，95%可信区间0.991 - 4.548，p = 0.051）。在亚组分析中，与CT或CC基因型患者相比，年龄≥60岁且ABCB1 1236 TT的患者≥2级PIPN的发生率更高（p = 0.027）。在多变量分析中，年龄≥60岁和ABCB1 1236 TT与≥2级PIPN显著相关（分别为p = 0.005和p = 0.034）。
ABCB1 1236 TT基因型和老年可能是PIPN的预测指标，这会降低癌症幸存者的生活质量。
