CYP2A13基因8种错义突变与肺癌易感性的关联研究  

Association between missense mutations of CYP2A13 gene and lung cancer susceptibility

作　　者：刘亭[1] 李朝辉[2] 谢章明[2] 徐迎春[2] 吴敏良[3] 徐笑红[4] 陈枢青[2] 

机构地区：[1]贵阳医学院药学院贵州省药物制剂重点实验室,贵阳550004 [2]浙江大学药学院药理毒理与生化药学研究所 [3]浙江大学医学院附属第二医院 [4]浙江省肿瘤医院检验科

出　　处：《浙江医学》2014年第17期1438-1442,共5页Zhejiang Medical Journal

基　　金：国家自然科学基金(81273578);国家科技重大专项基金(重大新药专项课题;2012ZX09506001-004);贵州省卫生厅科学技术基金项目(丹参与华法林相互作用的机制研究);贵州省科技厅贵州省科学技术基金项目(黔科合J字[2013]2034号)

摘　　要：目的探讨细胞色素p450 2A13(Cytochrome p450 2A13,CYP2A13)基因8种错义突变与肺癌易感性的相关性。方法采用以自然人群为基础的病例-对照方法,对2007-2011年间收集的91例肺癌病例以及140例年龄和性别相匹配的正常对照者进行研究。采用等位基因特异扩增法(Allele-Specific Amplification,ASA)对血液样本中CYP2A13基因的8种错义突变位点进行检测。结果在对照组和病例组之间,各错义突变位点的基因型频率均无统计学的差异(均P>0.05);p.Arg257Cys(12.1%vs11%)、p.Thr134_Leu135insThr(2.1%vs1.1%)、p.Arg101Gln(7.3%vs4.4%)、p.Phe453Tyr(2.2%vs1.1%)、p.Arg494Cys(2.9%vs1.1%)、p.Arg101Ter(6.6%vs2.2%)、p.Asp158Glu(2.1%vs1.1%)、p.Val323Leu(0.07%vs0%)。各错义突变位点的等位基因频率也均无统计学差异(均P>0.05);p.Arg257Cys(6.8%vs5.5%)、p.Thr134_Leu135insThr(1.1%vs0.5%)、p.Arg101Gln(4.0%vs2.2%)、p.Phe453Tyr(1.1%vs0.5%)、p.Arg494Cys(1.5%vs0.5%)、p.Arg101Ter(4.0%vs1.1%)、p.Asp158Glu(1.1%vs0.5%)、p.Val323Leu(0.4%vs0%)。结论中国汉族人群中存在CYP2A13基因错义突变,但CYP2A13基因错义突变与肺癌易感性可能不存在关联,这提示虽然CYP2A13在肺癌发生中起到了一定作用,但可能不是影响我国汉族人群肺癌易感性的主要因素,还存在其它因素的交互影响。Objective To investigate the association between missense mutations of CYP2A13 gene and lung cancer susceptibility. Methods Ninety one patients with lung cancer and 140 healthy subjects matched by age and sex were recruited from 2007 to 2011. Genomic DNA was isolated from peripheral blood samples, and a two- step al ele- specific amplification （ASA） method was applied to genotyping. Results There were no significant differences in genotype frequency of CYP2A13 missense polymorphism between cases and controls（P〉0.05）：p.Arg257Cys（12.1%vs 11%）, p.Thr134_Leu135insThr （2.1%vs 1.1%）, p.Arg101Gln（7.3% vs 4.4%）, p.Phe453Tyr （2.2% vs 1.1%）, p.Arg494Cys（2.9%vs 1.1%）, p.Arg101Ter （6.6% vs 2.2%）, p.Asp158Glu （2.1% vs 1.1%）, p.Val323Leu （0.07% vs 0%）. No differences existed in the al ele frequency between cases and controls （P〉0.05）： p.Arg257Cys （6.8% vs 5.5%）, p.Thr134_Leu135insThr （1.1% vs 0.5%）, p.Arg101Gln （4.0% vs 2.2%）, p. Phe453Tyr （1.1% vs 0.5%）, p.Arg494Cys （1.5% vs 0.5%）, p.Arg101Ter （4.0% vs 1.1%）, p.Asp158Glu （1.1% vs 0.5%）, p. Val323Leu （0.4% vs 0%）. Conclusion There are CYP2A13 missense polymorphisms in Chinese Han population, but these CYP2A13 missense polymorphisms might not be related to the susceptibility of lung cancer.

关 键 词：肺肿瘤/遗传学 多态性 错义突变 CYP2A13 CYP2A13 

分 类 号：R734.2[医药卫生—肿瘤]