Liu Di, Xu Wen, Ding Xi, Yang Yang, Su Bo, Fei Ke
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Department of Respirology and Critical Care Medicines, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
J Cancer. 2017 Oct 17;8(18):3785-3794. doi: 10.7150/jca.21151. eCollection 2017.
As a crucial cell cycle regulator and G2/M phase promotor, played an essential role in progression of chemotherapy related cell death. Platinum-based chemotherapy is still the first-line chemotherapy regimen for most advanced NSCLC patients. We aim to investigate the correlation of polymorphisms to the efficiency of platinum-based chemotherapy in Chinese advanced NSCLC patients. We enrolled 972 patients with advanced NSCLC, and extracted DNA from their peripheral blood for genotyping four tagSNPs which selected from the Hapmap database. We analyzed the association of four tagSNPs with efficiency of platinum-based chemotherapy. We found that rs2069429 and rs2069433 of were associated with the OS of advanced NSCLC patients. Patients with GG genotype of rs2069429 had longer OS than non-GG patients (HR=0.81, 95%CI=0.68-0.95, =0.009); and patients with AA genotype of rs2069433 had longer OS than non-AA patients (HR=0.78, 95%CI=0.61-0.98, =0.036). And the haplotype GAAA of was a putative factor in subgroup patients with clinical stage IV. The association of polymorphisms and toxicities after platinum-based chemotherapy was assessed. Rs2069433 and rs350104 were related with gastrointestinal toxicity of platinum-based chemotherapy. The patients with GG genotype of rs2069433 (=0.013) and/or non-GG genotype of rs350104 (=0.042) may have a severe gastrointestinal toxicity after chemotherapy, and then clinician may can reduce the dosage of chemotherapy agents to avoid sever toxicities in these patients. In summary, polymorphisms may contribute to the clinical efficiency of platinum-based chemotherapy in advanced NSCLC patients, and it is helpful for the personalized treatment.
作为一种关键的细胞周期调节因子和G2/M期促进因子,在化疗相关细胞死亡进程中发挥着重要作用。铂类化疗仍是大多数晚期非小细胞肺癌(NSCLC)患者的一线化疗方案。我们旨在研究中国晚期NSCLC患者中[具体基因名称未给出]多态性与铂类化疗疗效的相关性。我们纳入了972例晚期NSCLC患者,从其外周血中提取DNA,对从Hapmap数据库中选择的4个标签单核苷酸多态性(tagSNP)进行基因分型。我们分析了这4个tagSNP与铂类化疗疗效的关联。我们发现[具体基因名称未给出]的rs2069429和rs2069433与晚期NSCLC患者的总生存期(OS)相关。rs2069429的GG基因型患者的OS长于非GG基因型患者(风险比[HR]=0.81,95%置信区间[CI]=0.68 - 0.95,P=0.009);rs2069433的AA基因型患者的OS长于非AA基因型患者(HR=0.78,95%CI=0.61 - 0.98,P=0.036)。并且[具体基因名称未给出]的单倍型GAAA是临床IV期亚组患者的一个推定因素。我们评估了[具体基因名称未给出]多态性与铂类化疗后毒性的关联。rs2069433和rs350104与铂类化疗的胃肠道毒性相关。rs2069433的GG基因型患者(P=0.013)和/或rs350104的非GG基因型患者(P=0.042)化疗后可能有严重的胃肠道毒性,因此临床医生可以减少化疗药物剂量以避免这些患者出现严重毒性。总之,[具体基因名称未给出]多态性可能有助于晚期NSCLC患者铂类化疗的临床疗效,并且有助于个性化治疗。