GENETIC POLYMORPHISMS OF THE ADENOSINE TRIPHOSPHATE-BINDING CASSETTE TRANSPORTERS(ABCG2, ABCB1) AND GEFITINIB TOXICITY
GENETIC POLYMORPHISMS OF THE ADENOSINE TRIPHOSPHATE-BINDING CASSETTE TRANSPORTERS(ABCG2, ABCB1) AND GEFITINIB TOXICITY
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DOI：
10.18999/nagjms.74.1-2.133
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发表时间：
2012-02
影响因子：
0.9
通讯作者：
Mariko Tamura;M. Kondo;Mihoko Horio;M. Ando;H. Saito;Masashi Yamamoto;Y. Horio;Y. Hasegawa
中科院分区：
文献类型：
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作者：
Mariko Tamura;M. Kondo;Mihoko Horio;M. Ando;H. Saito;Masashi Yamamoto;Y. Horio;Y. Hasegawa
摘要 本研究的目的是研究吉非替尼治疗患者中 ABCG2 和 ABCB1 等位基因变异与皮肤毒性、腹泻、肝损伤和间质性肺疾病 (ILD) 之间的关联。对 83 名日本非小细胞肺癌患者进行了一项前瞻性临床研究。对 ABCG2 和 ABCB1 的多态性位点进行了基因分型，并评估了它们对吉非替尼毒性的影响。 ABCG2 34G>A与皮疹的发生有统计学相关性； 32 名至少具有一种变异 ABCG2 34G>A 等位基因（G/A 和 A/A）的患者中，有 13 名 (42%) 出现 2 级或更严重的皮疹，而 51 名对两个等位基因的野生型序列的参考等位基因 (G/G) 纯合的患者中，只有 10 名 (19%) 出现了这种情况 (P = 0.046)。严重毒性与 ABCG2 421C>A 和 ABCB1 3435C>T 的多态性之间没有显着相关性。结果表明 ABCG2 34G>A 可用于预测 2 级或更严重的皮疹。
ABSTRACT The purpose of this study is to investigate associations between allelic variations of ABCG2 and ABCB1 with skin toxicity, diarrhea, liver injury and interstitial lung disease (ILD) in gefitinib-treated patients. A prospective clinical study of 83 Japanese patients with non–small–cell lung cancer was performed. Polymorphic loci in ABCG2 and ABCB1 were genotyped, and their effects on gefitinib toxicities were evaluated. ABCG2 34G>A was statistically associated with occurrence of skin rash; 13 (42%) of the 32 patients with at least one variant ABCG2 34G>A allele (G/A and A/A) developed grade 2 or worse skin rash, whereas only 10 (19%) of 51 patients homozygous for the reference allele (G/G) for the wild-type sequence for both alleles did so (P = 0.046). There was no significant association between severe toxicities and polymorphisms of ABCG2 421C>A nor ABCB1 3435C>T. The results suggested that ABCG2 34G>A would be useful for predicting grade 2 or worse skin rash.