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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

李晓玉, 何斐, 叶超, 蔡琳. 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[J]. 肿瘤防治研究, 2014, 41(09): 1014-1020. DOI: 10.3971/j.issn.1000-8578.2014.09.013
引用本文: 李晓玉, 何斐, 叶超, 蔡琳. 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[J]. 肿瘤防治研究, 2014, 41(09): 1014-1020. DOI: 10.3971/j.issn.1000-8578.2014.09.013
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LI Xiaoyu, HE Fei, YE Chao, CAI Lin. Association between DNA Double-strand Break Repair Gene Polymorphisms and Prognosis of Non-small Cell Lung Cancer Patients[J]. Cancer Research on Prevention and Treatment, 2014, 41(09): 1014-1020. DOI: 10.3971/j.issn.1000-8578.2014.09.013
Citation: LI Xiaoyu, HE Fei, YE Chao, CAI Lin. Association between DNA Double-strand Break Repair Gene Polymorphisms and Prognosis of Non-small Cell Lung Cancer Patients[J]. Cancer Research on Prevention and Treatment, 2014, 41(09): 1014-1020. DOI: 10.3971/j.issn.1000-8578.2014.09.013
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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

  • 350004 福州，福建医科大学公共卫生学院

基金项目: 国家自然科学基金资助项目（30771845；81172766）
详细信息
    作者简介:

    李晓玉（1988-），女，硕士在读，主要从事肿瘤（分子）流行病学研究

    通讯作者:

    蔡琳，E-mail：cailin_cn@hotmail.com

  • 中图分类号: R734.2

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

  • Department of Epidemiology, School of Public Health, Fujian Medical University, Fuzhou 350004, China

摘要

    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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  • [1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009[J].CA Cancer J Clin,2009,59(4):225-49.
    [2] Butkiewicz D, Rusin M, Sikora B, et al. An association between DNA repair gene polymorphisms and survival in patients with resected non-small cell lung cancer[J]. Mol Biol Rep,2011,38(8):5231-41.
    [3] Kim M, Kang HG, Lee SY, et al. Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non-small-cell lung cancer[J]. Cancer Sci,2010,101(11):2436 -42.
    [4] Wu W, Li H, Wang H, et al. Effect of polymorphisms in XPD on clinical outcomes of platinum-based chemotherapy for Chinese non-small cell lung cancer patients[J]. PLoS One,2012,7(3): e33200.
    [5] Sun Z, Chen J, Aakre J, et al. Genetic variation in glutathione metabolism and DNA repair genes predicts survival of small-cell lung cancer patients[J]. Ann Oncol,2010,21(10):2011-6.
    [6] Brundage MD, Davies D, Mackillop WJ. Prognostic factors in nonsmall cell lung cancer: a decade of progress[J]. Chest,2002,122(3): 10 37-57.
    [7] Fan LH，Chen JL，Cai L. Study on the association between DNA double-strand break repair gene NBS1 polymorphisms and susceptibility on lung cancer[J].Zhonghua Liu Xing Bing Xue Za Zhi,2010,31(2):213-7.[樊丽辉, 陈俊磊, 蔡琳. DNA双链断裂修 复基因NBS1多态性与肺癌易感性的关联研究[J]. 中华流行病 学杂志,2010,31(2):213-7.]
    [8] Qian B, Zhang H, Zhang L, et al. Association of genetic polymorphisms in DNA repair pathway genes with non-small cell lung cancer risk[J].Lung Cancer,2011, 73(2):138-46.
    [9] Chen X,Fan LH,Qiu YF, et al.Association of the polymorphisms in DNA double-strand break repair gene XRCC4 with susceptibility of lung cancer[J].Zhong Liu, 2010,10(30):852-9.[陈星,樊丽辉,邱 月锋,等.DNA双链断裂修复基因XRCC4多态性与肺癌易感性 的关系[J].肿瘤,2010,10(30):852-9.]
    [10] Improta G, Sgambato A, Bianchino G, et al. Polymorphisms of the DNA repair genes XRCC1 and XRCC3 and risk of lung and colorectal cancer: a case-control study in a Southern Italian population[J]. Anticancer Res,2008, 28(5B):2941-6.
    [11] Ren S, Zhou S, Wu F, et al. Association between polymorphisms of DNA repair genes and survival of advanced NSCLC patients treated with platinum-based chemotherapy[J]. Lung Cancer,2012, 75 (1):102-9.
    [12] Matullo G, Dunning AM, Guarrera S, et al.DNA repair polymorphisms and cancer risk in non-smokers in a cohort study[J]. Carcinogenesis,2006, 27(5):997-1007.
    [13] Wang Y, Cortez D, Yazdi P, et al. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures[J]. Genes Dev,2000, 14(8):927-39.
    [14] Futaki M, Liu JM. Chromosomal breakage syndromes and the BRCA1 genome surveillance complex[J]. Trends Mol Med,2001, 7( 12):560-5.
    [15] Lu M, Lu J, Yang X, et al.Association between the NBS1 E185Q polymorphism and cancer risk: a meta-analysis[J]. BMC Cancer,2009,9:124.
    [16] Xu JL, Hu LM, Huang MD, et al. Genetic variants of NBS1 predict clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer in Chinese[J]. Asian Pac J Cancer Prev,2012, 13(3):851-6.
    [17] Rosell R, Skrzypski M, Jassem E, et al. BRCA1: a novel prognostic factor in resected non-small-cell lung cancer[J]. PLoS One,2007, 2(11):e1129.
    [18] Nakamura H, Haruki T, Adachi Y, et al. Smoking affects prognosis after lung cancer surgery[J]. Surg Today,2008, 38(3):227-31.
    [19] Sardari Nia P, Weyler J, Colpaert C,et al. Prognostic value of smoking status in operated non-small cell lung cancer[J]. Lung Cancer,2005, 47(3):351-9.
    [20] Baser S, Shannon VR, Eapen GA, et al.Smoking cessation after diagnosis of lung cancer is associated with a beneficial effect on performance status[J]. Chest,2006, 130(6):1784-90.
    [21] Kawai H, Tada A, Kawahara M, et al. Smoking history before surgery and prognosis in patients with stage IA non-smallcell lung cancer-a multicenter study[J]. Lung Cancer,2005, 49 (1):63-70.
    [22] Park SL, Bastani D, Goldstein BY, et al. Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers[J]. Carcinogenesis,2010, 31(7):1264-71.
    [23] Manuguerra M, Matullo G, Veglia F,et al. Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions[J]. Carcinogenesis,2007, 28(2):414-22.
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  • 刊出日期:  2014-09-24

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