Chen Juan, Wang Zhan, Zou Ting, Cui Jiajia, Yin Jiye, Zheng Wei, Jiang Wuzhong, Zhou Honghao, Liu Zhaoqian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China.
Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, P. R. China.
Oncotarget. 2016 Aug 23;7(34):55741-55756. doi: 10.18632/oncotarget.9688.
Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/ C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients.
已发表的数据显示，关于广泛研究的多态性与铂类化疗反应之间的关联，结果并不一致。我们的研究旨在通过检测更大样本量的单核苷酸多态性（SNP）基因型并汇总全面的合并分析，来提供这些关联的可靠结论。通过Sequenom MassARRAY对1024例非小细胞肺癌（NSCLC）患者的8个基因中的13个SNP进行了基因分型。39项已发表的研究和我们的研究被纳入荟萃分析。携带XRCC1 G1196的GA或GG基因型的患者比AA基因型携带者对化疗的反应更好（基因分型研究：比值比[OR]=0.72，95%置信区间[CI]：0.53-0.96，P=0.028；荟萃分析：OR=0.74，95%CI：0.62-0.89，P=0.001）。与携带CC基因型的患者相比，携带XRCC1 C580T的CT或TT基因型的患者可能对铂类化疗更敏感（OR=0.54，95%CI：0.37-0.80，P=0.002）。与携带CT或TT基因型的患者相比，XRCC3 C18067T携带者的CC基因型对铂类化疗表现出更大的耐药性（OR=0.69，95%CI：0.52-0.91，P=0.009）。我们的研究表明，在NSCLC患者的铂类化疗个体化中，应关注XRCC1 G1196A/C580T和XRCC3 C18067T。
