Abyarghamsari Mahdiye, Hosseini Shirazi Farshad, Tavakoli-Ardakani Maria, Rezvani Hamid, Mirzaei Hamid Reza, Salamzadeh Jamshid
Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medial Sciences, Tehran, Iran.
Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2019 Fall;18(4):2163-2171. doi: 10.22037/ijpr.2019.1100827.
This study was designed to evaluate the effect of excision repair cross complementing group 1 (ERCC1) rs11615 codon 118C/T gene polymorphisms on treatment outcomes in Iranian patients receiving oxaliplatin-based regimens for colorectal (CRC) and gastric cancers (GC). Patients, who were candidates to receive oxaliplatin-based chemotherapy, entered into the study. In 2-week intervals, the patients received combination regimen of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) for 3 months. ERCC1 rs11615 codon 118C/T polymorphism was tested by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method using patients' peripheral blood lymphocytes. The tumor response to chemotherapy was evaluated by examining the size of the tumor using CT scan. Association between response rates, according to the RECIST criteria, and patients' genotypes was evaluated. Any relationship between response rate and possible explanatory factors was also determined. Overall, 40 patients (13 females (32.5%), and 27 males (67.5%)) enrolled in the study. Four patients (10.0%) carried the homo-zygous mutation (T/T genotype), ten patients (25.0%) were heterozygous (C/T genotype), and twenty-six patients (65%) were homo-zygous (C/C genotype). Response rate were 30.77%, 20.00%, and 0.00% for the genotypes C/C, C/T, and T/T, respectively. No significant association between response rate and genotypes was observed ( = 0.64). Patients with well- and moderately-differentiated histological grade of the tumor showed a better response rate (100.00% of 2 patients and 66.66% of 12 patients, respectively) compared to those with poorly differentiated (0.00% of 26 patients) histological grade ( < 0.001). Further multicenter studies are recommended to confirm conclusively our findings.
本研究旨在评估切除修复交叉互补基因1（ERCC1）rs11615密码子118C/T基因多态性对接受基于奥沙利铂方案治疗的伊朗结直肠癌（CRC）和胃癌（GC）患者治疗结局的影响。符合接受基于奥沙利铂化疗条件的患者纳入本研究。患者每隔2周接受奥沙利铂、氟尿嘧啶和亚叶酸钙（FOLFOX）联合方案治疗3个月。采用限制性片段长度多态性聚合酶链反应（RFLP-PCR）方法，利用患者外周血淋巴细胞检测ERCC1 rs11615密码子118C/T多态性。通过CT扫描检查肿瘤大小来评估化疗的肿瘤反应。根据实体瘤疗效评价标准（RECIST）评估缓解率与患者基因型之间的关联。还确定了缓解率与可能的解释因素之间的任何关系。总体而言，40例患者（13例女性（32.5%）和27例男性（67.5%））纳入本研究。4例患者（10.0%）携带纯合突变（T/T基因型），10例患者（25.0%）为杂合子（C/T基因型），26例患者（65%）为纯合子（C/C基因型）。C/C、C/T和T/T基因型的缓解率分别为30.77%、20.00%和0.00%。未观察到缓解率与基因型之间存在显著关联（P = 0.64）。与低分化组织学分级的患者（26例患者中为0.00%）相比，肿瘤组织学分级为高分化和中分化的患者显示出更好的缓解率（2例患者中为100.00%，12例患者中为66.66%）（P < 0.001）。建议进一步开展多中心研究以最终证实我们的研究结果。
