DNA双链断裂修复基因遗传多态性与非小细胞肺癌预后关联研究

李晓玉; 何斐; 叶超; 蔡琳

doi:10.3971/j.issn.1000-8578.2014.09.013

DNA双链断裂修复基因遗传多态性与非小细胞肺癌预后关联研究

Association between DNA Double-strand Break Repair Gene Polymorphisms and Prognosis of Non-small Cell Lung Cancer Patients

摘要

摘要: 目的探讨DNA双链断裂修复（DSBR）基因遗传多态性与非小细胞肺癌（NSCLC）预后的关联。方法应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和TaqMan探针技术检测679 例NSCLC新发病例的DSBR 10个SNP（rs6869366、rs1056503、rs3734091、rs861539 、rs861537、rs1799794、rs16942、rs144848、rs1805794、rs2735383）的基因分型，应用Kaplan-Meier、Log rank 检验和Cox回归模型进行预后分析。结果患者总体5年生存率为29.8%（95%CI：26.1%~33.5%）。化疗患者携带XRCC3 rs861539 CT+TT基因型的死亡风险低于携带CC基因型患者（MST：32月vs. 60 月HR=0.629，95%CI：0.411~0.962，P=0.032；aHR=0.623，95%CI：0.399~0.973，P=0.038）；鳞癌患者携带BRCA1 rs16942 AG+GG等位基因型比携带AA基因型的预后差（MST：24月vs. 31月；aHR=1.622，95%CI：1.139~2.310，P=0.007）；非吸烟女性腺癌患者携带NBS1 rs2735383GC+CC基因型较携带G G 基因型的死亡风险低（MST：41月 v s . 32 月；aHR=0.420，95%CI：0.247~0.714，P = 0 . 0 0 1 ）；携带X R C C 3r s 8 6 1 5 3 9CT+TT基因型的临床早期病例较携带CC基因型的死亡风险降低（ aHR= 0 . 4 4 4 ， 9 5%CI ：0.192~1.025，P=0.057）；男性吸烟的早期患者携带NBS1 rs1805794 CG+GG基因型比CC基因型的死亡风险高（aHR=2.768，95%CI：1.273~6.017，P=0.010）；携带XRCC3 rs861537 AA基因型的临床晚期病例较携带GG基因的死亡风险增加（aHR=1.750，95%CI：1.021~3.001，P=0.042）。联合分析发现，患者携带4个或5个不利基因型比携带≤3个不利基因型的死亡风险增加（aHR=1.153，95%CI：1.005~1.322，Ptrend=0.042）。结论 DSBR基因遗传多态性可作为NSCLC患者预后评价的参考。

Abstract: Objective To investigate the association between DNA double-strand break repair gene （DSBR）polymorphisms and prognosis of patients with non-small cell lung cancer(NSCLC). Methods PCR-RFLP and TaqMan probe technique were used to identify the polymorphism of 10 SNPs in DSBR gene, rs6869366, rs1056503, rs3734091, rs861539, rs861537, rs1799794, rs16942, rs144848, rs1805794 and rs2735383, in 679 NSCLC patients. Prognosis was analyzed by Kaplan-Meier, Log-rank test and Cox regression model. Results The estimated 5-year OS of NSCLC patients was 29.8%(95%CI：26.1%-33.5%). Subgroup analysis revealed that XRCC3rs861539 CT+TT was associated with lower death risk than CC in patients treated with chemotherapy（MST：32 vs. 60 months；HR=0.629，95%CI：0.411-0.962，P=0.032；aHR=0.623，95%CI:0.399-0.973，P=0.038）. BRCA1 rs16942 AG+GG was associated with worse survival than AA in patients with the squamous subtype（MST：24 vs. 31months；aHR=1.622，95%CI:1.139-2.310，P=0.007）. NBS1rs2735383GC+CC was associated with higher survival than GG in non-smoking female wtih adenocarcinoma（MST：41 vs. 32 months；aHR=0.420，95%CI:0.247-0.714，P=0.001）. XRCC3 rs861539CT+TT was associated with lower death risk than CC in clinic early-stage patients（aHR=0.444，95%CI:0.192-1.025，P=0.057）. NBS1rs1805794 CG+GG was associated with higher death risk than CC in clinic early-stage smoking men（aHR=2.768，95%CI:1.273-6.017，P=0.01）. XRCC3 rs861537AG or AA was associated with higher death risk than GG in clinic advanced patients（aHR=1.750，95%CI:1.021-3.001，P=0.042）. NSCLC patients with four or five unfavorable genotypes had a significantly worse OS than those with less than three unfavorable genotypes （aHR=1.153，95%CI:1.005-1.322, Ptrend=0.042）. Conclusion DSBR gene polymorphism may be a reference for the prognosis evaluation of NSCLC patients.

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