Yoon Kyong-Ah, Woo Sang Myung, Hong Eun Kyung, Jung Mee Kyung, Park Weon Seo, Bae Kieun, Han Sung-Sik, Kim Tae Hyun, Koh Young Hwan, Park Sang-Jae, Lee Woo Jin
Research Institute, Goyang, Republic of Korea.
Oncology. 2015;89(6):345-50. doi: 10.1159/000439222. Epub 2015 Sep 30.
Gemcitabine-based chemotherapy is regarded as the standard treatment for biliary tract cancer (BTC). Potential biomarkers for gemcitabine response include the activities of cytidine deaminase (CDA), human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (DCK), and ribonucleotide reductase M1 (RRM1). Here, we investigated whether single nucleotide polymorphisms (SNPs) in their encoding genes were associated with the efficacy of gemcitabine chemotherapy in treating BTC.
We retrospectively evaluated 11 SNPs in the CDA, hENT1, DCK, human concentrative nucleoside transporter 3 (hCNT3), and RRM1 genes in 80 patients with unresectable, metastatic, or recurrent BTC who were treated with gemcitabine plus cisplatin.
After the results were adjusted for clinical predictors, the variant allele of rs1048977 in the CDA gene was associated with tumor response in a dominant model (OR, 0.23; 95% CI, 0.06-0.93; p = 0.039). No significant association was detected between the 11 SNPs and grade 3/4 toxicity.
Our findings suggest that the polymorphism of CDA may be a potential predictive marker for the efficacy of gemcitabine-based chemotherapy in patients with BTC.
吉西他滨为基础的化疗被视为胆道癌（BTC）的标准治疗方法。吉西他滨反应的潜在生物标志物包括胞苷脱氨酶（CDA）、人平衡核苷转运体1（hENT1）、脱氧胞苷激酶（DCK）和核糖核苷酸还原酶M1（RRM1）的活性。在此，我们研究了其编码基因中的单核苷酸多态性（SNP）是否与吉西他滨化疗治疗BTC的疗效相关。
我们回顾性评估了80例接受吉西他滨联合顺铂治疗的不可切除、转移性或复发性BTC患者的CDA、hENT1、DCK、人浓缩核苷转运体3（hCNT3）和RRM1基因中的11个SNP。
在对临床预测因素进行校正后，CDA基因中rs1048977的变异等位基因在显性模型中与肿瘤反应相关（OR，0.23；95%CI，0.06 - 0.93；p = 0.039）。未检测到11个SNP与3/4级毒性之间存在显著关联。
我们的研究结果表明，CDA的多态性可能是BTC患者以吉西他滨为基础的化疗疗效的潜在预测标志物。
