Associations between UGT1A1*6/*28 polymorphisms and irinotecan-induced severe toxicity in Chinese gastric or esophageal cancer patients
Associations between UGT1A1*6/*28 polymorphisms and irinotecan-induced severe toxicity in Chinese gastric or esophageal cancer patients
复制标题
UGT1A1*6/*28 多态性与中国胃癌或食管癌患者伊立替康引起的严重毒性的关联
DOI：
10.1007/s12032-013-0630-8
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发表时间：
2013-09-01
期刊：
影响因子：
3.4
通讯作者：
Shen, Lin
中科院分区：
文献类型：
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作者：
Gao, Jing;Zhou, Jun;Shen, Lin
本研究旨在探讨中国晚期胃癌、食道癌患者UDP-葡萄糖醛酸基转移酶(UGT)1A1基因多态性与伊立替康毒性的关系。对42例接受伊立替康化疗的胃癌患者和91例食道癌患者进行了UGT1A1*6和UGT1A1*28基因分型。分析UGT1A1*6/*28基因多态性对严重腹泻和中性粒细胞减少症的影响。在我们的队列中，UGT1A1*6/*28个变异在胃癌和食道癌中的总发生率分别为38.1%(GA：31.0%；AA：6.9%)、28.6%(Ta6/TA7：26.2%；TA7：2.4%)和33.0%(GA：28.6%；AA：4.4%)、25.3%(Ta6/TA7：23.1%；TA7/TA7：2.2%)。共有10例患者(胃癌：9.5%，4/42；食道癌：6.6%，6/91)出现严重腹泻；35例患者(胃癌：35.7%，15/42；食道癌：22.0%，20/91)出现严重的中性粒细胞减少。由于患者数量有限，未进行UGT1A1基因分型与严重腹泻的统计分析。在胃癌中，似乎只有UGT1A1*6变异与严重中性粒细胞减少症有关(P=0.042)，而在食道癌患者中，UGT1A1*6(P=0.011)或UGT1A1*28(P=0.026)变异与严重中性粒细胞减少症显著相关。UGT1A1*6变异与胃癌和食道癌的严重中性粒细胞减少症密切相关，但UGT1A1*28变异与胃癌和食道癌的严重中性粒细胞减少症的相关性在本研究中并不一致，这一点将在未来的大样本中得到验证。
The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced gastric or esophageal cancer patients. The genotypes of UGT1A1*6 and UGT1A1*28 were analyzed by PCR amplification and Sanger sequencing in 42 gastric and 91 esophageal cancer patients receiving irinotecan-containing chemotherapy. The influences of UGT1A1*6/*28 polymorphisms on severe diarrhea and neutropenia were analyzed. The overall incidence of UGT1A1*6/*28 variants in gastric cancer and esophageal cancer was 38.1 % (GA: 31.0 %; AA: 6.9 %), 28.6 % (TA6/TA7: 26.2 %; TA7/TA7: 2.4 %) and 33.0 % (GA: 28.6 %; AA: 4.4 %), 25.3 % (TA6/TA7: 23.1 %; TA7/TA7: 2.2 %) in our cohort, respectively. A total of 10 patients (gastric cancer: 9.5 %, 4/42; esophageal cancer: 6.6 %, 6/91) had severe diarrhea and 35 patients (gastric cancer: 35.7 %, 15/42; esophageal cancer: 22.0 %, 20/91) had severe neutropenia. Statistic analysis between UGT1A1 genotyping and severe diarrhea was not conducted due to the limited number of patients. For gastric cancer, it seemed that only UGT1A1*6 variant was associated with severe neutropenia (P = 0.042), while among esophageal cancer patients, UGT1A1*6 (P = 0.011) or UGT1A1*28 (P = 0.026) variants were significantly associated with severe neutropenia. UGT1A1*6 variant was closely associated with severe neutropenia both in gastric cancer and in esophageal cancer, but the association between UGT1A1*28 variant and severe neutropenia in gastric and esophageal cancer was not consistent in this study, which would be validated in the future large samples.