Pongmaneratanakul Skolchart, Tanasanvimon Suebpong, Pengsuparp Thitima, Areepium Nutthada
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. Email:
Asian Pac J Cancer Prev. 2017 Mar 1;18(3):857-861. doi: 10.22034/APJCP.2017.18.3.857.
Purpose: Biliary tract cancer (BTC)is an aggressive disease with a poor prognosis. Most patients are diagnosed at an advanced stage for which curative surgery is not possible and gemcitabine-platinum chemotherapy is the treatment of choice for advanced cases. Several studies had focused on biomarkers to predict response from platinum drugs in lung cancer, but information is limited for BTC. In this study, two single nucleotide polymorphisms (SNPs) in the copper transporter (CTR1) and excision repair cross-complementary group 1 (ERCC1) genes were investigated as predictive biomarkers of objective response to gemcitabine-platinum. Methods: This cohort study aimed to assess any associations of genetic polymorphisms of these proteins active in drug pathway with treatment response in advanced BTC patients. Twenty six patients were enrolled. DNA was extracted from peripheral blood and genetic polymorphisms were assessed by Taqman allelic discrimination assay. Response was evaluated according to RECIST version 1.1. Results: For the CTR1 polymorphism, GT was the most common genotype (61.5%) followed by GG (34.6%), and TT (3.8%). For the ERCC1 polymorphism, only 2 genotypes were found, CC and CT at 57.7% and 42.3%, respectively. Genetic polymorphisms were not found to be singly associated with response. However, when the 2 genetic polymorphisms were combined, GG/CC showed a higher response rate than the others (p=0.018, Fisher’s Exact Test). Conclusion: This is the first study to show an association between CTR1 and ERCC1 polymorphisms and response to gemcitabine-platinum in advanced BTC patients. These polymorphisms might be used as biomarkers to predict response in such cases in the future.
胆管癌（BTC）是一种侵袭性疾病，预后较差。大多数患者在晚期被诊断出来，无法进行根治性手术，吉西他滨 - 铂类化疗是晚期病例的首选治疗方法。多项研究聚焦于预测肺癌中铂类药物反应的生物标志物，但关于BTC的信息有限。在本研究中，对铜转运蛋白（CTR1）和切除修复交叉互补组1（ERCC1）基因中的两个单核苷酸多态性（SNP）进行了研究，作为吉西他滨 - 铂类客观反应的预测生物标志物。方法：这项队列研究旨在评估这些参与药物通路的蛋白质的基因多态性与晚期BTC患者治疗反应之间的任何关联。招募了26名患者。从外周血中提取DNA，并通过Taqman等位基因鉴别分析评估基因多态性。根据RECIST 1.1版评估反应。结果：对于CTR1多态性，GT是最常见的基因型（61.5%），其次是GG（34.6%）和TT（3.8%）。对于ERCC1多态性，仅发现两种基因型，CC和CT，分别为57.7%和42.3%。未发现基因多态性与反应单独相关。然而，当将这两种基因多态性结合时，GG/CC显示出比其他基因型更高的反应率（p = 0.018，Fisher精确检验）。结论：这是第一项表明CTR1和ERCC1多态性与晚期BTC患者对吉西他滨 - 铂类反应之间存在关联的研究。这些多态性未来可能用作预测此类病例反应的生物标志物。
