UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients
UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients
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DOI：
10.1007/s10147-008-0821-z
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发表时间：
2009-04-01
影响因子：
3.3
通讯作者：
Inui, Ken-ichi
中科院分区：
文献类型：
--
作者：
Onoue, Masahide;Terada, Tomohiro;Inui, Ken-ichi
在服用伊立替康的患者中，UDP-葡萄糖醛酸基转移酶1家族多肽A1(UGT1A1)的基因多态导致不良事件的个体差异，并且这些多态的分布显示出很大的种族差异。溶质载体有机阴离子转运体家族成员1b1(SLCO1B1)基因的变异也对亚洲癌症患者伊立替康的处置有显著影响。在这项研究中，我们评估了UGT1A1和SLCO1B1基因多态与日本癌症患者伊立替康相关性中性粒细胞减少症的相关性。用直接测序法测定UGT1A1(*60、*28、*6、*27)和SLCO1B1(*1b、*5、*15)等位基因。严重的中性粒细胞减少是指在伊立替康治疗的第一个周期中观察到的事件。29名患者(22%)观察到严重的中性粒细胞减少。UGT1A1*6纯合子6例，杂合子48例，UGT1A1*28纯合子仅1例。UGT1A1*6纯合子与严重中性粒细胞减少症的高风险相关(优势比[OR]，7.78；95%可信区间[CI]，1.36至44.51)。未发现严重中性粒细胞减少症与其他UGT1A1或SLCO1B1基因多态相关，提示UGT1A1*6基因多态是日本癌症患者伊立替康引起严重中性粒细胞减少症的潜在预测因子。
Gene polymorphisms of the UDP-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) contribute to individual variations in adverse events among patients administered irinotecan, and the distribution of the polymorphisms shows large interethnic differences. Variation in the solute carrier organic anion-transporter family, member 1B1 (SLCO1B1) gene also has a significant effect on the disposition of irinotecan in Asian cancer patients. In the present study, we evaluated the association of genetic polymorphisms of UGT1A1 and SLCO1B1 with irinotecanrelated neutropenia in Japanese cancer patients.One hundred and thirty-five consecutive patients treated with irinotecan were enrolled. Genotypes of UGT1A1 (*60, *28, *6, and *27) and SLCO1B1 (*1b, *5, and haplotype *15) were determined by direct sequencing. Severe neutropenia refers to events observed during the first cycle of irinotecan treatment.Severe neutropenia was observed in 29 patients (22%). Six patients were homozygous and 48 heterozygous for UGT1A1*6. Only 1 patient was homozygous for UGT1A1*28. Homozygosity for UGT1A1*6 was associated with a high risk of severe neutropenia (odds ratio [OR], 7.78; 95% confidence interval [CI], 1.36 to 44.51). No significant association was found between severe neutropenia and other UGT1A1 polymorphisms or SLCO1B1 polymorphisms.These findings suggest that the UGT1A1*6 polymorphism is a potential predictor of severe neutropenia caused by irinotecan in Japanese cancer patients.