【摘要】 目的位于染色体22q12.2区域的MTMR3(myotubularin related protein 3)基因是调控肌维管束蛋白表达的基因,MTMR3基因过度表达与肿瘤等疾病发生有关。本研究旨结合表达数量性状(expression Quati tatire Trait Loci,eQTL)信息探讨MTMR3基因多态性与非吸烟者肺癌易感性的关系,为探究肺癌的发病机制提供依据。方法对肺癌易感区域22q12.2进行连锁不平衡和eQTL分析,筛选具有调控基因表达的致病位点并预测其调控的基因。本研究采用病例对照研究方法,病例为2013-03-05-2014-12-30辽宁省肿瘤医院(96例)、中国医科大学附属第一医院(92例)、中国医科大学附属第四医院(90例)、沈阳军区总医院(95例)和人民解放军沈阳二0二医院(88例)5所三甲级医院的原发性肺癌患者461例(病例组),同期社区中健康对照472名(对照组)。应用TaqMan基因分型技术对rs36605位点进行基因分型。采用t检验比较年龄在病例组与对照组间分布的差异,采用χ~2检验比较性别、各基因型以及各环境暴露因素在病例组与对照组间分布的差异,应用Logistic回归计算OR值及其95%置信区间(CI)。结果经eQTL分析得到rs36605位点是MTMR3基因的一个顺式eQTL,rs36605位点可能与MTMR3基因的表达有关。以TT基因型为参照,AT基因型(OR=0.81,95%CI为0.60~1.10,P=0.178)和AA基因型(OR=1.85,95%CI为0.61~5.59,P=0.276)与肺癌的患病风险无统计学关联。也未发现在显性模型(OR=0.85,95%CI为0.63~1.15,P=0.291)以及隐形模型(OR=1.94,95%CI为0.64~5.86,P=0.238)中存在此关联。试验验证了烹饪油烟暴露增加了肺癌的患病风险,调整OR=1.61,95%CI为1.06~2.45,P=0.025,但未发现烹饪油烟暴露与rs36605位点多态性之间存在交互作用,P>0.05。结论试验未发现,22q12.2区域内的rs36605位点多态性与非吸烟者肺癌的易感性有关,尚不能得到MTMR3基因多态性与非吸烟者肺癌的易感性有关。更多还原

【Abstract】 OBJECTIVE The MTMR3 gene located in 22q12.2 and it controls the expression of the myotubularin.The overexpression of MTMR3 gene is associated with tumor and other diseases.The aim of this study was to investigate the association between polymorphism of MTMR3 gene and lung cancer susceptibility in non-smokers by combining expression quantitative trait information,which would provide a better scientific basis for exploring the pathogenesis of lung cancer.METHODS The linkage disequilibrium analysis and eQTL analysis were used to select the causative loci in 22q12.2 and predict its control gene.There were 461 patients who were diagnosed with lung cancer between March 5,2013 to December 30,2014 from Liaoning Tumor Hospital and other four third-grade class-A hospitals,and the 472 controls came from the community in the same period.The TaqMan genotyping technology was used to genotype the rs36605.The T test was used to compare the distribution between cases and controls of age.The χ~2 test was performed to compare the distribution between cases and controls of the genotypes,environmental risk factors and sex.Using unconditional logistic regression to calculate the odds ratios(OR)with 95%confidence intervals(CI).RESULTS The eQTL analysis results showed that rs36605 was a cis-eQTL of MTMR3 gene,which regulated expression of MTMR3 gene.The AT(OR=0.81,95%CI:0.60-1.10,P=0.178)and AA(OR=1.85,95%CI:0.61-5.59,P=0.276)genotype were not associated with the risk of lung cancer with TT genotype as reference.It was also found that there was no such association in the dominant model(OR=0.85,95%CI:0.63-1.15,P=0.291)and the recessive model(OR=1.94,95%CI0.64-5.86,P=0.238).This study found that exposure to cooking oil increased the risk of lung cancer,adjusted OR=1.61,95%CI:1.06-2.45,P=0.025.There was no significant interaction between cooking oil fume exposure and polymorphism of rs36605,P>0.05.CONCLUSIONS This study found no association between rs36605 and lung cancer susceptibility in non-smokers.The association of genetic polymorphisms of MTMR3 and risk of lung cancer in non-smokers remains uncertain.更多还原