ABCG2 多态性对非小细胞肺癌患者吉非替尼临床疗效和毒性的影响。
Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients.
机构信息
Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
出版信息
Pharmacogenomics. 2011 Feb;12(2):159-70. doi: 10.2217/pgs.10.172.
Abstract
AIMS
The current study investigates whether or not functional polymorphisms in the ATP-binding cassette transporter gene ABCG2 might affect gefitinib activity and/or toxicity in non-small-cell lung cancer (NSCLC) patients.
MATERIALS & METHODS: Towards this end, ABCG2 polymorphisms and expression were assessed in DNA and tumors from 94 NSCLC patients treated with gefitinib, whereas their associations with toxicity/response and time-to-progression/overall survival were evaluated using Pearson-χ(2) and log-rank-test, respectively.
RESULTS
Patients carrying an ABCG2 -15622T/T genotype or harboring at least one TT copy in the ABCG2 (1143C/T, -15622C/T) haplotype developed significantly more grade 2/3 diarrhea (p < 0.01). No associations were found between polymorphisms and outcome. Consistently, ABCG2 protein levels in tumors were not significantly different between patients harboring different ABCG2 variants.
CONCLUSION
The ABCG2 -15622C/T polymorphism and ABCG2 (1143C/T, -15622C/T) haplotype resulted in a gefitinib-dependent, moderate-to-severe diarrhea suggesting that these pharmacogenetic markers should be considered to optimize NSCLC treatment.
摘要
目的
本研究旨在探讨三磷酸腺苷结合盒转运蛋白基因 ABCG2 的功能多态性是否会影响非小细胞肺癌（NSCLC）患者接受吉非替尼治疗的疗效和/或毒性。
材料与方法
为此，对 94 例接受吉非替尼治疗的 NSCLC 患者的 DNA 和肿瘤中的 ABCG2 多态性和表达进行了评估，使用 Pearson-χ(2)检验和对数秩检验分别评估了它们与毒性/反应和进展时间/总生存期的关系。
结果
携带 ABCG2-15622T/T 基因型或 ABCG2(1143C/T、-15622C/T)单倍型至少有一个 TT 拷贝的患者发生 2/3 级腹泻的比例明显更高（p<0.01）。多态性与结局之间未发现相关性。同样，不同 ABCG2 变异患者的肿瘤中 ABCG2 蛋白水平无显著差异。
结论
ABCG2-15622C/T 多态性和 ABCG2(1143C/T、-15622C/T)单倍型导致吉非替尼依赖性中重度腹泻，提示这些药物遗传学标志物应考虑用于优化 NSCLC 治疗。
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