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福建省汉族人群肺癌相关microRNA基因SNP与吸烟交互作用研究
作者:何斐 林剑波 俞婷婷 张鑫 刘志强 熊为旻 蔡琳

摘要:

目的  探讨福建省汉族人群肺癌相关microRNA (miRNA)基因SNP位点rs11614913、rs2910164、rs12894467、rs7372209及rs895819与吸烟的交互作用关系。方法  采用病例-对照研究设计,收集2006年1月至2012年1月经病理确诊的汉族新发原发性肺癌患者1 053例;按照性别、年龄进行频数成组匹配,同期选取探视病例组患者的汉族亲友及在福建省福州市苍霞社区卫生服务中心进行健康体检的汉族人群作为对照组,共1 058名。调查研究对象性别、身高、体重、文化程度、婚姻状况、肿瘤家族史、肺部疾病史、吸烟、饮茶、饮酒等情况。经知情同意后,均采集空腹静脉血5 ml,应用基质辅助激光解析电离时间飞行质谱技术(MALDI-TOF-MS)进行rs11614913、rs2910164、rs12894467、rs7372209及rs895819位点多态基因分型。以是否发生原发性肺癌为因变量,以SNP位点为自变量构建多因素非条件logistic回归模型。利用叉生分析探讨SNP位点与吸烟之间可能存在的联合作用;利用超额相对危险度(RERI)分析吸烟与SNP位点显、隐性模型的相加交互作用。结果  病例组吸烟量P50(P25~P75)为30.00 (0.00~56.00)包年,高于对照组[0.00 (0.00~20.48)包年](Z=14.57,P< 0.001);病例组不吸烟者的被动吸烟指数P50(P25~P75)为11.40 (0.00~25.00),高于对照组[0.00 (0.00~13.11)](Z=10.71,P<0.001)。rs11614913、rs2910164、rs12894467、rs7372209及rs895819位点检出率在病例组中分别为95.82%(1 009/1 053)、97.72%(1 029/1 053)、97.82%(1 030/1 053)、97.15%(1 023/1 053)和96.01%(1 011/1 053);对照组中分别为98.11%(1 038/1 058)、98.96%(1 047/1 058)、98.30% (1 040/1 058)、98.68%(1 044/1 058)和98.02%(1 037/1 058)。rs11614913位点的显性遗传模型中,TT基因型与吸烟联合可增加原发性肺癌的发病风险(OR=4.04,95%CI:2.67~6.12);隐性遗传模型中,CC基因型与吸烟联合可增加原发性肺癌的发病风险(OR=4.76,95%CI:3.16~7.17)。rs12894467位点的显性遗传模型中,TT基因型与吸烟联合可增加原发性肺癌的发病风险(OR=2.98,95 %CI :2.28~3.90);隐性遗传模型中,CC基因型与吸烟联合可增加原发性肺癌的发病风险(OR=1.94,95%CI:1.10~3.43)。rs2910164位点的显性遗传模型中,CC基因型与吸烟联合可增加原发性肺癌的发病风险(OR=2.18,95%CI:1.60~2.98);隐性遗传模型中,GG基因型与吸烟联合可增加原发性肺癌的发病风险(OR=3.29,95%CI:2.16~5.03)。吸烟与rs12894467位点显、隐性基因模型相乘交互项的联合作用均存在统计学意义(χ2=8.58 ,P=0.003 ;χ2=4.76,P=0.040)。结论  rs11614913、rs12894467及rs2910164位点多态性与福建省汉族原发性肺癌发生存在潜在关联。

关键词:微RNAs;多态性,单核苷酸;肺肿瘤;易感性;病例-对照研究

Abstract:

Objective  To investigate the interaction on smoking and the lung cancer related genes miR-196a2 rs11614913, miR-146a rs2910164, miR-300 rs12894467, miR-26a-1 rs7372209, miR-27a rs895819 in Fujian Han population.Methods  From January 2006 to January 2012, by using a hospital-based case-control study, 1 053 cases were pathologically diagnosed as primary lung cancer from the Department of Thoracic Surgery and 1 058 controls were randomly selected from the visiting relatives of patients and visiting people of Cangxia community health service of Fuzhou city according to match with age and genders. They were recruited for questionnaires survey and genotyping detection. Research objects of genders, height, weight, cultural degree, marital status, family history of cancer, lung disease history, smoking, drinking tea, drinking, and so on. After informed consent, we collected 5 ml fasting venous blood from every object, used MALDI-TOF-MS to analysis genotyping of polymorphic loci. Logistic regression model was constructed by using SNP as independent variable, and the multiple factors were constructed with different loci. The possible association between SNP and cigarette smoking was analyzed by using the crossover analysis. The relative excess risk of interaction (RERI) were used to analyze on smoking and SNP loci additive interaction of dominant and recessive genetic models.Results  Smokers in case group who smoked P50(P25-P75)30.00 (0.00-56.00) packages in a year were higher than control group (0.00(0.00 - 20.48) pack years) (Z=14.57,P<0.001). Passive smoking index for non-smokers was 11.40(0.00-25.00), higher than the controls (0.00(0.00-13.11)) (Z=10.71,P<0.001). Site detection rate of rs11614913, rs2910164, rs12894467, rs7372209 and rs895819 in cases was 95.82%(1 009/1 053), 97.72%(1 029/1 053), 97.82% (1 030/1 053), 97.15% (1 023/1 053) and 96.01% (1 011/1 053) respectively. The controls were 98.11% (1 038/1 058), 98.96% (1 047/1 058), 98.30% (1 040/1 058), 98.68% (1 044/1 058) and 98.02% (1 037/1 058) respectively. rs11614913 dominant genetic model, TT genotype and smoking could increase the risk of primary lung cancer (OR=4.04, 95%CI: 2.67 -6.12). Recessive genetic model, CC genotype and smoking increased the incidence of primary lung cancer risk (OR=4.76, 95%CI: 3.16 -7.17). rs12894467 dominant genetic model, TT genotype and smoking could increase the risk (OR=2.98, 95%CI: 2.28 -3.90) in primary lung cancer. In recessive genetic model, CC genotype and smoking increased the incidence of primary lung cancer risk (OR=1.94, 95% CI: 1.10-3.43). Dominant genetic model of rs2910164, CC genotype and smoking could increase the risk (OR=2.18, 95% CI: 1.60 -2.98) in primary lung cancer. Recessive genetic model, GG genotype and smoking increased the incidence of primary lung cancer risk (OR=3.29, 95% CI: 2.16 -5.03). Especially rs12894467 dominant and recessive gene model and genders, smoking and there were combined effects(χ2=8.58, P=0.003; χ2=4.76, P=0.040).Conclusion  Rs11614913, rs12894467 and rs2910164 polymorphism were potentially associated with primary lung cancer in Fujian Han population.

Key words: MicroRNAs;Polymorphism, single nucleotide;Lung neoplasm;Susceptibility;Case-control studies

发表日期:2016/2

引用本文:

图/表:

  • 10.3760/cma.j.issn.0253-9624.2016.02.013.T001

    10.3760/cma.j.issn.0253-9624.2016.02.013.T001

  • 10.3760/cma.j.issn.0253-9624.2016.02.013.T002:表2 肺癌病例组和对照组基本情况比较

    10.3760/cma.j.issn.0253-9624.2016.02.013.T002:表2 肺癌病例组和对照组基本情况比较

  • 10.3760/cma.j.issn.0253-9624.2016.02.013.T003:表3 micro RAN基因rs11614913、rs2910164及rs12894467位点显、隐性模型与吸烟的联合作用对肺癌发病风险影响的logistic回归模型分析结果

    10.3760/cma.j.issn.0253-9624.2016.02.013.T003:表3 micro RAN基因rs11614913、rs2910164及rs12894467位点显、隐性模型与吸烟的联合作用对肺癌发病风险影响的logistic回归模型分析结果

参考文献:

[1]SlabyO, Bienertova-VaskuJ, SvobodaM, et al. Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer[J]. J Cell Mol Med, 2012, 16(1): 8-21. DOI: 10.1111/j.1582-4934.2011.01359.x.
[2]LuJ, GetzG, MiskaEA, et al. MicroRNA expression profiles classify human cancers[J]. Nature, 2005, 435(7043): 834-838.
[3]KangZ, LiY, HeX, et al. Quantitative assessment of the association between miR-196a2 rs11614913 polymorphism and cancer risk: evidence based on 45, 816 subjects[J]. Tumour Biol, 2014, 35(7): 6271-6282. DOI: 10.1007/s13277-014-1822-3.
[4]钟山亮,蒋胜高,赵建华.Pre-miR-146a rs2910164基因多态性与癌症易感性的荟萃分析[J].临床检验杂志,2014,32(1):41-44. DOI: 10.13602/j.cnki.jcls.2014.01.022
[5]张新伟,潘善东,冯耀良,等.微小RNA前体区域基因多态与肝细胞肝癌遗传易感性关联的研究[J].中华预防医学杂志,2011,45(3):239-243. DOI: 10.3760/cma.j.issn.0253-9624.2011.03.010.
[6]López-LópezE, Gutiérrez-Caminoá, Pi?ánMá, et al. Pharmacogenetics of microRNAs and microRNAs biogenesis aachinery in pediatric acute lymphoblastic leukemia[J]. PLoS One, 2014, 9(3):e91261. DOI: 10.1371/journal.pone.0091261.
[7]YeY, WangKK, GuJ, et al. Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk[J]. Cancer Prev Res(Phila), 2008, 1(6): 460-469. DOI: 10.1158/1940-6207.CAPR-08-0135.
[8]武阳丰,马冠生,胡永华,等.中国居民的超重和肥胖流行现状[J].中华预防医学杂志,2005,39(5):316-320.
[9]XuY, GuL, PanY, et al. Different effects of three polymorphisms in microRNAs on cancer risk in asian population: evidence from published literatures[J]. PLoS One, 2013, 8(6):e65123. DOI: 10.1371/journal.pone.0065123.
[10]JiaY, ZangA, ShangY, et al. MicroRNA-146a rs2910164 polymorphism is associated with susceptibility to non-small cell lung cancer in the Chinese population[J]. Med Oncol, 2014, 31(10): 194. DOI: 10.1007/s12032-014-0194-2.
[11]JeonHS, LeeYH, LeeSY, et al. A common polymorphism in pre-microRNA-146a is associated with lung cancer risk in a Korean population[J]. Gene, 2014, 534(1): 66-71. DOI: 10.1016/j.gene.2013.10.014.
[12]VinciS, GelminiS, PratesiN, et al. Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers[J]. Clin Chem Lab Med, 2011, 49(12): 2073-2080. DOI: 10.1515/CCLM.2011.708.
[13]ChenZ, XuL, YeX, et al. Polymorphisms of microRNA sequences or binding sites and lung cancer: a meta-analysis and systematic review[J]. PLoS One, 2013, 8(4): e61008. DOI: 10.1371/journal.pone.0061008.
[14]ZhangD, YangG, ChenX, et al. mir-300 promotes self-renewal and inhibits the differentiation of glioma stem-Like cells[J]. J Mol Neurosci, 2014, 53(4): 637-644. DOI: 10.1007/s12031-014-0230-x.
[15]ZhangT, XieS, ZhuJH, et al.Association of IL10 -819C>T and -592C>A Polymorphisms with Non-Hodgkin Lymphoma Susceptibility: Evidencefrom Published Studies[J].J Cancer, 2015, 6(8): 709-716. DOI: 10.7150/jca.11745.eCollection2015.
[16]XiongXD, LuoXP, ChengJ, et al. A genetic variant in pre-miR-27a is associated with a reduced cervical cancer risk in southern Chinese women[J]. Gynecol Oncol, 2014, 132(2): 450-454. DOI: 10.1016/j.ygyno.2013.12.030.
[17]ZhangJ, HuangX, XiaoJ, et al. Pri-miR-124 rs531564 and pri-miR-34b/c rs4938723 polymorphisms are associated with decreased risk of esophageal squamous cell carcinoma in Chinese populations[J]. PLoS One, 2014, 9(6): e100055. DOI: 10.1371/journal.pone.0100055.
[18]YoonKA, YoonH, ParkS, et al. The prognostic impact of microRNA sequence polymorphisms on the recurrence of patients with completely resected non-small cell lung cancer[J]. J Thorac Cardiovasc Surg, 2012, 144(4): 794-807. DOI: 10.1016/j.jtcvs.2012.06.030.
[19]MaJY, YanHJ, YangZH, et al. Rs895819 within miR-27a might be involved in development of non-Small cell lung cancer in the Chinese Han population[J]. Asian Pac J Cancer Prev, 2015, 16(5): 1939-1944.

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