DNA修复基因和多药耐药基因1（MDR1）基因多态性与非小细胞肺癌化疗反应及生存的相关性
Associations of polymorphisms in DNA repair genes and MDR1 gene with chemotherapy response and survival of non-small cell lung cancer.
作者信息
Du Yan, Su Tong, Zhao Lijun, Tan Xiaojie, Chang Wenjun, Zhang Hongwei, Cao Guangwen
机构信息
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Department of Pulmonary Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
出版信息
PLoS One. 2014 Jun 16;9(6):e99843. doi: 10.1371/journal.pone.0099843. eCollection 2014.
OBJECTIVES
We aimed to determine the associations of genetic polymorphisms of excision repair cross-complementation group 1 (ERCC1) rs11615, xeroderma pigmentosum group D (XPD/ERCC2) rs13181, X-ray repair cross complementing group 1 (XRCC1) rs25487, XRCC3 rs1799794, and breast cancer susceptibility gene 1 (BRCA1) rs1799966 from the DNA repair pathway and multiple drug resistance 1 (MDR1/ABCB1) rs1045642 with response to chemotherapy and survival of non-small cell lung cancer (NSCLC) in a Chinese population.
MATERIALS AND METHODS
A total of 352 NSCLC patients were enrolled to evaluate the associations of the six SNPs with response to chemotherapy and overall survival. Logistic regressions were applied to test the associations of genetic polymorphisms with response to chemotherapy in 161 advanced NSCLC patients. Overall survival was analyzed in 161 advanced and 156 early stage NSCLC patients using the Kaplan-Meier method with log-rank test, respectively. Multivariate Cox proportional hazards model was performed to determine the factors independently associated with NSCLC prognosis.
RESULTS
BRCA1 rs1799966 minor allele C (TC+CC vs. TT, OR = 0.402, 95% CI = 0.204-0.794, p = 0.008) and MDR1/ABCB1 rs1045642 minor allele A (GA +AA vs. GG, OR = 0.478, 95% CI = 0.244-0.934, p = 0.030) were associated with a better response to chemotherapy in advanced NSCLC patients. Survival analyses indicated that BRCA1 rs1799966 TC+CC genotypes were associated with a decreased risk of death (HR = 0.617, 95% CI = 0.402-0.948, p = 0.028) in advanced NSCLC patients, and the association was still significant after the adjustment for covariates. Multivariate Cox regression analysis showed that ERCC1 rs11615 AA genotype (P = 0.020) and smoking (p = 0.037) were associated with increased risks of death in early stage NSCLC patients after surgery.
CONCLUSIONS
Polymorphisms of genes in DNA repair pathway and MDR1 could contribute to chemotherapy response and survival of patients with NSCLC.
目的
我们旨在确定来自DNA修复途径的切除修复交叉互补组1（ERCC1）rs11615、着色性干皮病D组（XPD/ERCC2）rs13181、X射线修复交叉互补组1（XRCC1）rs25487、XRCC3 rs1799794以及乳腺癌易感基因1（BRCA1）rs1799966的基因多态性和多药耐药1（MDR1/ABCB1）rs1045642与中国人群非小细胞肺癌（NSCLC）化疗反应及生存情况之间的关联。
材料与方法
共纳入352例NSCLC患者，以评估这6个单核苷酸多态性（SNP）与化疗反应及总生存的关联。应用逻辑回归分析检测161例晚期NSCLC患者基因多态性与化疗反应的关联。分别采用Kaplan-Meier法和对数秩检验分析161例晚期和156例早期NSCLC患者的总生存情况。采用多变量Cox比例风险模型确定与NSCLC预后独立相关的因素。
结果
在晚期NSCLC患者中，BRCA1 rs1799966次要等位基因C（TC+CC与TT相比，OR = 0.402，95%CI = 0.204 - 0.794，p = 0.008）和MDR1/ABCB1 rs1045642次要等位基因A（GA +AA与GG相比，OR = 0.478，95%CI = 0.244 - 0.934，p = 0.030）与更好的化疗反应相关。生存分析表明，在晚期NSCLC患者中，BRCA1 rs1799966的TC+CC基因型与死亡风险降低相关（HR = 0.617，95%CI = 0.402 - 0.948，p = 0.028），在调整协变量后该关联仍具有统计学意义。多变量Cox回归分析显示，ERCC1 rs11615的AA基因型（P = 0.020）和吸烟（p = 0.037）与早期NSCLC患者术后死亡风险增加相关。
结论
DNA修复途径相关基因和MDR1的多态性可能影响NSCLC患者的化疗反应及生存。
Zotero 插件