Genetic polymorphisms associated with oxaliplatin-induced peripheral neurotoxicity in Japanese patients with colorectal cancer
Genetic polymorphisms associated with oxaliplatin-induced peripheral neurotoxicity in Japanese patients with colorectal cancer
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DOI：
10.5414/cp201851
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发表时间：
2013-06-01
影响因子：
0.8
通讯作者：
Ando, Yuichi
中科院分区：
文献类型：
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作者：
Oguri, Tomoyo;Mitsuma, Ayako;Ando, Yuichi
目的：通过对韩国患者的全基因组关联研究（GWAS），报道了严重奥沙利铂诱导的慢性周围神经毒性（OXCPN）（2级，持续5 ~ 7天或3级）与8个基因（TAC1、FOXC1、ITGA1、ACYP2、DLEU7、BTG4、CAMK2N1和FARS2）的9个单核苷酸多态性（snp）之间的药物基因组学关联。本研究旨在探索OXCPN的可靠预测因子，从而改善转移性结直肠癌（CRC）的治疗。方法：我们回顾性研究了70名接受奥沙利铂化疗的日本结直肠癌患者OXCPN的药物基因组学特征，并更新了我们之前对ERCCI （C118T， rs11615和C8092A， rs3212986）和GSTP 1 （Ile105Val, rs1695）多态性的分析结果。结果：单因素分析提示，重度OXCPN与ACYP2基因中rs843748、FARS2基因中rs17140129以及无糖尿病（DM）存在潜在关联（p分别为0.056、0.072和0.029）。严重的OXCPN与其他7个snp中的任何一个都没有关联。多元logistic回归分析显示，重度OXCPN发生风险增加与rs17140129和DM缺失相关（p分别为0.034和0.030）。在最新的分析中，TAG1中ERCCI （C118T, rs11615）和rs10486003的多态性与1级OXCPN的启动时间相关（p分别为0.024和0.049）。结论：严重OXCPN与rs17140129显著相关，在韩国GWAS患者中发现，在日本患者中发现。非糖尿病患者更容易发生OXCPN。在最新的分析中，ERCCI多态性与OXCPN发病时间之间的关联是显著的。
Objective: Pharmacogenomic associations between severe oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) (Grade 2 lasting for > 7 days or Grade 3) and 9 single nucleotide polymorphisms (SNPs) in 8 genes (TAC1, FOXC1, ITGA1, ACYP2, DLEU7, BTG4, CAMK2N1, and FARS2) were reported by the genome-wide association study (GWAS) in Korean patients. The present study was designed to explore reliable predictors of OXCPN and thereby improve the management of metastatic colorectal cancer (CRC). Methods: We retrospectively investigated pharmacogenomic characteristics of OXCPN in 70 Japanese patients with CRC who received oxaliplatin-based chemotherapy and updated the results of our previous analysis of ERCCI (C118T, rs11615 and C8092A, rs3212986) and GSTP 1 (Ile105Val, rs1695) polymorphisms. Results: Univariate analysis suggested potential associations of severe OXCPN with rs843748 in ACYP2 and rs17140129 in FARS2, as well as with the absence of diabetes mellitus (DM) (p = 0.056, 0.072, and 0.029, respectively). There was no association between severe OXCPN and any of the 7 other SNPs. Multiple logistic regression analysis showed that an increased risk of severe OXCPN was related to rs17140129 and the absence of DM (p = 0.034 and 0.030, respectively). On updated analysis, polymorphisms of ERCCI (C118T, rs11615) and rs10486003 in TAG1 were associated with time to the on-set of Grade 1 OXCPN (p = 0.024 and 0.049, respectively). Conclusions: Severe OXCPN is significantly related to rs17140129, found in the GWAS of Korean patients, in Japanese patients. Patients without DM are more likely to have OXCPN. The association between ERCCI polymorphism and time to the onset of OXCPN was significant on updated analysis.