He Fei, Lin Jianbo, Yu Tingting, Zhang Xin, Liu Zhiqiang, Xiong Weimin, Cai Lin
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350108, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2016 Feb;50(2):168-74. doi: 10.3760/cma.j.issn.0253-9624.2016.02.013.
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.
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.
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(χ(2)=8.58, P=0.003; χ(2)=4.76, P=0.040).
Rs11614913, rs12894467 and rs2910164 polymorphism were potentially associated with primary lung cancer in Fujian Han population.
探讨吸烟与福建汉族人群肺癌相关基因miR-196a2 rs11614913、miR-146a rs2910164、miR-300 rs12894467、miR-26a-1 rs7372209、miR-27a rs895819之间的相互作用。
2006年1月至2012年1月，采用基于医院的病例对照研究，选取胸外科病理诊断为原发性肺癌的患者1053例，按年龄和性别匹配，从福州市仓霞社区卫生服务中心患者的探视亲属及来访人员中随机选取1058例对照。对研究对象进行问卷调查和基因分型检测。调查内容包括研究对象的性别、身高、体重、文化程度、婚姻状况、癌症家族史、肺部疾病史、吸烟、饮茶、饮酒等情况。经知情同意后，采集每位研究对象5ml空腹静脉血，采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）分析多态性位点的基因分型。以单核苷酸多态性（SNP）为自变量构建Logistic回归模型，并对不同位点构建多因素模型。采用交叉分析方法分析SNP与吸烟之间的可能关联。采用交互作用的相对超额危险度（RERI）分析吸烟与SNP位点显性和隐性遗传模型的相加交互作用。
病例组中每年吸烟量P50（P25-P75）为30.00（0.00-56.00）包年的吸烟者高于对照组（0.00（0.00-20.48）包年）（Z=14.57，P<0.001）。非吸烟者的被动吸烟指数为11.40（0.00-25.00），高于对照组（0.00（0.00-13.11））（Z=10.71，P<0.001）。病例组中rs11614913、rs2910164、rs12894467、rs7372209和rs895819的位点检测率分别为95.82%（1009/1053）、97.72%（1029/1053）、97.82%（1030/1053）、97.15%（1023/1053）和96.01%（1011/1053）。对照组中分别为98.11%（1038/1058）、98.96%（1047/1058）、98.30%（1040/1058）好98.68%（1044/1058）和98.02%（1037/1058）。rs11614913显性遗传模型中，TT基因型与吸烟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基因型与吸烟增加原发性肺癌发病风险（OR=4.76，95%CI：3.16-7.17）。rs12894467显性遗传模型中，TT基因型与吸烟可增加原发性肺癌发病风险（OR=2.98，95%CI：2.28-3.90）。隐性遗传模型中，CC基因型与吸烟增加原发性肺癌发病风险（OR=1.94，95%CI：1.10-3.43）。rs2910164显性遗传模型中，CC基因型与吸烟可增加原发性肺癌发病风险（OR=2.18，95%CI：1.60-2.98）。隐性遗传模型中，GG基因型与吸烟增加原发性肺癌发病风险（OR=3.29，95%CI：2.16-5.03）。尤其是rs12894467显性和隐性基因模型与性别、吸烟存在联合效应（χ(2)=8.58，P=0.003；χ(2)=4.76，P=0.040）。
rs11614913、rs12894467和rs2910164基因多态性可能与福建汉族人群原发性肺癌相关。
