中国汉族人群CYP2A13、GSTP1、MPO基因多态性与肺癌易感性关系研究
|
摘要
肺癌是世界范围内的常见恶性肿瘤。随着工业化和城市化的进程,我国肺癌的防控形势也越趋严峻。积极开展肺癌预防在21世纪的肿瘤防控战略中具有重要意义。对肺癌的大量研究已经证实肺癌是一种典型的环境相关疾病,吸烟
和大气污染等是肺癌的主要危险因素。但是肺癌的群体流行病学研究也表明了不同个体间对共同的环境致癌因素具有不同的易感性。随着人类基因组计划的完成,能够反映个体间基因差异的单核苷酸多态性(single neucleotide polymorphism, SNP)受到广泛重视并成为重要的功能基因组学研究内容。充分利用SNP公共数据库的信息,研究肺癌相关候选基因,寻找与肺癌发生具有相关性的SNP位点是研究肺癌易感性分子标志物的有效策略。
肺癌的发生与发展是一个多因素介入的多步骤过程。烟草等各种环境致癌物在体内要经过一系列代谢酶的复杂作用,体外实验发现谷胱甘肽-S-转移酶P1(glutathione-S-transferase P1, GSTP1)、髓过氧化物酶(Myeloperoxidase, MPO)等代谢酶基因的多态性影响了烟草致癌物的代谢,由此推论个体对肺癌的易感性在一定程度上可能取决于外来化学致癌物在不同个体内的代谢差异,特别是在癌变的始动阶段,这种差异可能对肺癌的发生起着关键作用。关于慢性病发病机制的一个学说认为常见基因变异引起常见疾病。我们假设：参与烟草等环境致癌物代谢的基因常见多态性与肺癌的发生具有一定相关性,而具有相关性的这种常见多态性位点在理论上有望成为筛选肺癌易感人群的分子标志物。
为了验证上述假设,我们在肺癌的病因、表现、发病机制的认识基础上选择了在人体中具有代谢烟草前致癌物作用并在肺组织中充分表达的代谢酶GSTP1、细胞色素P450酶2A13(cytochrome P450 2A13, CYP2A13)、MPO作为候选基因,采用分子流行病学病例-对照研究方法研究其常见多态性与肺癌易感性的关系。国际人类基因组单体型图计划(International HapMap project)的顺利进行为开展中国人群基因多态性的研究提供了大量有用信息。我们在充分利用SNP公共数据库信息的基础上,对上述基因进行了整体分析,综合运用“以序列为基础”和“以图谱为基础”的选点策略,选择了基本可以覆盖上述基因常见多态性信息的SNP位点(GSTP1的单体型标签SNPs rs762803、rs749174、rs1695、rs4891,CYP2A13的标签SNPs rs8192789和rs1645690,MPO的标签SNPsrs7208693),采用了Taqman探针基因分型技术对比分析了266例中国汉族肺癌人群及307例年龄、性别相匹配的健康对照者的基因型分布,并应用TA克隆测序技术验证了Taqman探针基因分型技术的准确性,对基因型分型结果应用单元多因素logistic回归模型统计分析其与肺癌易感性的关系。对得到广泛研究的GSTP1 rs1695位点及MPO G-463A位点应用Meta分析的方法进行了系统评价。在对CYP2A13的基因rs8192789位点分析中我们发现了同源序列干扰的现象,进一步应用TA克隆测序技术研究了同源序列对CYP2A13基因SNP研究的影响。
结果显示我们得到的基因型数据与HapMap数据库中公布的北京汉族人群基因型数据是一致的。MPO rs7208693与肺癌不具有相关性；CYP2A13的标签SNPs rs1645690与非吸烟人群的肺癌发生具有明显相关性(adjust OR=0.448,95%CI0.208～0.967,p=0.041)；GSTP1的单体型标签SNPs rs762803、rs749174、rs1695、rs4891在两组人群的分布均具有差异性,利用Phase 2软件构建了其单体型,分析发现一个常见单体型CACA与吸烟人群的肺癌易感性具有关联(adjustOR=1.53,95%CI 1.04～2.25,p=0.033),由其构成的双倍型与吸烟人群的相关性更趋明显。对GSTP1进行的以单体型为基础的分析表明其符合常染色体隐性遗传模式。对MPO G-463A的Meta分析表明这两个位点与肺癌易感性不具有明显相关性。对CYP2A13的基因部分序列克隆测序的结果表明,CYP2A13的同源序列可能干扰了关于SNP的研究,dbSNP数据库中一些上传的位点可能是不存在的。
综上所述,我们充分利用了SNP公共数据库的信息,首次研究了上述三个基因常见多态性与肺癌易感性的关系,发现了一个与肺癌具有关联的位于CYP2A13基因的危险多态性位点以及位于GSTP1基因的一个危险单体型,其有望成为筛查肺癌易感人群的分子标记物,即肺癌易感性SNPs。
Lung cancer is the most common malignant tumor all over the world. With the development of the industry and urbanization process in Chian, we also face the more and more serious state to control and prevent the tumor. It is very intersting for the control and prevention of cancer to deal with lung cancer in the 21 century. It has been well established that lung caner is an enviroment-associated disease caused by mainly tabacco smoking and air pollution. Otherwise, it also indicate that variant susceptibility exist between individuals in the common carcinogen-enviroment exposure by the epidemiologic study. With the complement of human genomic project, the study on the single neucleotide polymorphism (SNP), which can reflect the variance between individuals, was think highly of one most important post-genomic project. To research the candidated gene and look for the SNPs associated with lung caner susecptibility on the basis of information of SNP database is a valid method.
The carcinogenesis and process of lung cancer is an multi-step caused by multitude factors. The carcinogens such as tobacco smoking,will go through complex process by a series of carcinogen-metabolizing enzymes. It has been found that the polymorphisms of some metabolizing enzymes, such as glutathione-S-transferase PI (GSTP1), Myeloperoxidase(MPO) can effect the metabolazing for the tobacco carcinogens. So, it can be infered that The genetic variations at carcinogen-metabolizing enzymes may lead to interindividual differences at the level of internal carcinogenic dose and lead to differential risk in the individuals with similar exposures, and especially in the initial step, the variations may play an important role. In the light of common disease-common variant hypothesis, we hypothesis also that, there is association between the common polymorphisms of some metabolazing enzymes gene and lung cancer susceptibility, and the common gene polymorphisms may be the candidated biomarkers for the scan of the risk individuals.
To validat the hypothesis, we select the metabolizing enzyme gene GSTP1, MPO and cytochrome P450 2A13(CYP2A13) as the candidated gene which play an important role in tobacco carcinoges metabolization and expressed in human lung tissue, to investigate the association between common polymorphisms and lung cancer risk in Chinese population, using a case-control analysis of 266 subjects with lung cancer and 307 controls with no personal history of the disease. With the process of International HapMap project, we can retrieve a lot of information for the research on Chinese gene polymorphisms. We analysed the 3 gene thoroughly according to the SNP data retrieved from the database and select the SNPs to study using the sequence-based and HapMap-based method syntheticly. The tagSNPs rs7208693 for MPO, tagSNPs rs1645690 and rs8192789 for CYP2A13, and the haplotype-tagging SNPs rs1695, rs4891, rs762803, rs749174 for GSTP1 were selected, these SNPs can reflect the common polymorphisms of the 3 genes. Taqman assays was used to genotype the the genetic polymorphisms for the 266 patients and 307 controls, and the genotyping method was validated by TA cloning and sequencing. Unconditional logistic regression method was used to evaluate the distribution of the genetic polymorphisms between the 2 groups and the association with lung cancer after adjusting for confounders. We evaluated the relationship between MPO G-463A, GSTP1 rs1695 and lung cancer risk by Meta analysis.We found the interference caused by homologous sequences during the study for the rs8192789 of CYP2A13, so we furtherly researched the interfering effect to CYP2A13 SNP study caused by homologous sequences using TA cloning and sequencing method.
The frequency of the 6 SNPs we tested was consistent with the data of Han-Chinese of Beijing released by HapMap database. The tagSNPs rs1645690 of CYP2A13 showed association between lung caner risk and non-smokers(adjust OR =0.448,95%CI 0.208～0.967,p=0.041), not the tagSNPs rs7208693 of MPO. The all 4 Haplotype-tagging SNPs, rs1695, rs4891, rs762803 and rs749174, showed association with lung cancer susceptibility in the smokers. Phase 2 sofrware was used to reconsrtuct the haplotype for GSTP1, and the haplotype(CACA) showed an increased risk of lung cancer among the smokers(adjust OR=1.53,95% CI 1.04～2.25,p=0.033). Furthermore, the diplotype analyses also demonstrated the significant association beween the risk haplotype and lung cancer. The risk haplotypes cosegregate with one or more biologically functional polymorphisms and it corresponds to a recessive inheritance mode. The results of Meta analysis indicate that the polymorphisms of MPO G-463A and GSTP1 rs1695 were not significantly associated with lung cancer risk. We cloned and sequenced the sequence of CYP2A13 gene, and the outcome indicate that the homologous sequences may interfere with the SNP study and some published SNPs in dbSNPs may not exist.
In conclusion, our study firstly investigated the association between the common polymorhpisms of the 3 candidated genes and lung cancer risk according to the SNPs information published. We found a risk SNPs of CYP2A13 and a risk haplotype of GSTP1 ssociated with lung caner, and these polymorphisms may be candidated SNP markers for lung cancer susceptibility in Chinese, which can be defined lung cancer risk SNPs
和大气污染等是肺癌的主要危险因素。但是肺癌的群体流行病学研究也表明了不同个体间对共同的环境致癌因素具有不同的易感性。随着人类基因组计划的完成,能够反映个体间基因差异的单核苷酸多态性(single neucleotide polymorphism, SNP)受到广泛重视并成为重要的功能基因组学研究内容。充分利用SNP公共数据库的信息,研究肺癌相关候选基因,寻找与肺癌发生具有相关性的SNP位点是研究肺癌易感性分子标志物的有效策略。
肺癌的发生与发展是一个多因素介入的多步骤过程。烟草等各种环境致癌物在体内要经过一系列代谢酶的复杂作用,体外实验发现谷胱甘肽-S-转移酶P1(glutathione-S-transferase P1, GSTP1)、髓过氧化物酶(Myeloperoxidase, MPO)等代谢酶基因的多态性影响了烟草致癌物的代谢,由此推论个体对肺癌的易感性在一定程度上可能取决于外来化学致癌物在不同个体内的代谢差异,特别是在癌变的始动阶段,这种差异可能对肺癌的发生起着关键作用。关于慢性病发病机制的一个学说认为常见基因变异引起常见疾病。我们假设：参与烟草等环境致癌物代谢的基因常见多态性与肺癌的发生具有一定相关性,而具有相关性的这种常见多态性位点在理论上有望成为筛选肺癌易感人群的分子标志物。
为了验证上述假设,我们在肺癌的病因、表现、发病机制的认识基础上选择了在人体中具有代谢烟草前致癌物作用并在肺组织中充分表达的代谢酶GSTP1、细胞色素P450酶2A13(cytochrome P450 2A13, CYP2A13)、MPO作为候选基因,采用分子流行病学病例-对照研究方法研究其常见多态性与肺癌易感性的关系。国际人类基因组单体型图计划(International HapMap project)的顺利进行为开展中国人群基因多态性的研究提供了大量有用信息。我们在充分利用SNP公共数据库信息的基础上,对上述基因进行了整体分析,综合运用“以序列为基础”和“以图谱为基础”的选点策略,选择了基本可以覆盖上述基因常见多态性信息的SNP位点(GSTP1的单体型标签SNPs rs762803、rs749174、rs1695、rs4891,CYP2A13的标签SNPs rs8192789和rs1645690,MPO的标签SNPsrs7208693),采用了Taqman探针基因分型技术对比分析了266例中国汉族肺癌人群及307例年龄、性别相匹配的健康对照者的基因型分布,并应用TA克隆测序技术验证了Taqman探针基因分型技术的准确性,对基因型分型结果应用单元多因素logistic回归模型统计分析其与肺癌易感性的关系。对得到广泛研究的GSTP1 rs1695位点及MPO G-463A位点应用Meta分析的方法进行了系统评价。在对CYP2A13的基因rs8192789位点分析中我们发现了同源序列干扰的现象,进一步应用TA克隆测序技术研究了同源序列对CYP2A13基因SNP研究的影响。
结果显示我们得到的基因型数据与HapMap数据库中公布的北京汉族人群基因型数据是一致的。MPO rs7208693与肺癌不具有相关性；CYP2A13的标签SNPs rs1645690与非吸烟人群的肺癌发生具有明显相关性(adjust OR=0.448,95%CI0.208～0.967,p=0.041)；GSTP1的单体型标签SNPs rs762803、rs749174、rs1695、rs4891在两组人群的分布均具有差异性,利用Phase 2软件构建了其单体型,分析发现一个常见单体型CACA与吸烟人群的肺癌易感性具有关联(adjustOR=1.53,95%CI 1.04～2.25,p=0.033),由其构成的双倍型与吸烟人群的相关性更趋明显。对GSTP1进行的以单体型为基础的分析表明其符合常染色体隐性遗传模式。对MPO G-463A的Meta分析表明这两个位点与肺癌易感性不具有明显相关性。对CYP2A13的基因部分序列克隆测序的结果表明,CYP2A13的同源序列可能干扰了关于SNP的研究,dbSNP数据库中一些上传的位点可能是不存在的。
综上所述,我们充分利用了SNP公共数据库的信息,首次研究了上述三个基因常见多态性与肺癌易感性的关系,发现了一个与肺癌具有关联的位于CYP2A13基因的危险多态性位点以及位于GSTP1基因的一个危险单体型,其有望成为筛查肺癌易感人群的分子标记物,即肺癌易感性SNPs。
Lung cancer is the most common malignant tumor all over the world. With the development of the industry and urbanization process in Chian, we also face the more and more serious state to control and prevent the tumor. It is very intersting for the control and prevention of cancer to deal with lung cancer in the 21 century. It has been well established that lung caner is an enviroment-associated disease caused by mainly tabacco smoking and air pollution. Otherwise, it also indicate that variant susceptibility exist between individuals in the common carcinogen-enviroment exposure by the epidemiologic study. With the complement of human genomic project, the study on the single neucleotide polymorphism (SNP), which can reflect the variance between individuals, was think highly of one most important post-genomic project. To research the candidated gene and look for the SNPs associated with lung caner susecptibility on the basis of information of SNP database is a valid method.
The carcinogenesis and process of lung cancer is an multi-step caused by multitude factors. The carcinogens such as tobacco smoking,will go through complex process by a series of carcinogen-metabolizing enzymes. It has been found that the polymorphisms of some metabolizing enzymes, such as glutathione-S-transferase PI (GSTP1), Myeloperoxidase(MPO) can effect the metabolazing for the tobacco carcinogens. So, it can be infered that The genetic variations at carcinogen-metabolizing enzymes may lead to interindividual differences at the level of internal carcinogenic dose and lead to differential risk in the individuals with similar exposures, and especially in the initial step, the variations may play an important role. In the light of common disease-common variant hypothesis, we hypothesis also that, there is association between the common polymorphisms of some metabolazing enzymes gene and lung cancer susceptibility, and the common gene polymorphisms may be the candidated biomarkers for the scan of the risk individuals.
To validat the hypothesis, we select the metabolizing enzyme gene GSTP1, MPO and cytochrome P450 2A13(CYP2A13) as the candidated gene which play an important role in tobacco carcinoges metabolization and expressed in human lung tissue, to investigate the association between common polymorphisms and lung cancer risk in Chinese population, using a case-control analysis of 266 subjects with lung cancer and 307 controls with no personal history of the disease. With the process of International HapMap project, we can retrieve a lot of information for the research on Chinese gene polymorphisms. We analysed the 3 gene thoroughly according to the SNP data retrieved from the database and select the SNPs to study using the sequence-based and HapMap-based method syntheticly. The tagSNPs rs7208693 for MPO, tagSNPs rs1645690 and rs8192789 for CYP2A13, and the haplotype-tagging SNPs rs1695, rs4891, rs762803, rs749174 for GSTP1 were selected, these SNPs can reflect the common polymorphisms of the 3 genes. Taqman assays was used to genotype the the genetic polymorphisms for the 266 patients and 307 controls, and the genotyping method was validated by TA cloning and sequencing. Unconditional logistic regression method was used to evaluate the distribution of the genetic polymorphisms between the 2 groups and the association with lung cancer after adjusting for confounders. We evaluated the relationship between MPO G-463A, GSTP1 rs1695 and lung cancer risk by Meta analysis.We found the interference caused by homologous sequences during the study for the rs8192789 of CYP2A13, so we furtherly researched the interfering effect to CYP2A13 SNP study caused by homologous sequences using TA cloning and sequencing method.
The frequency of the 6 SNPs we tested was consistent with the data of Han-Chinese of Beijing released by HapMap database. The tagSNPs rs1645690 of CYP2A13 showed association between lung caner risk and non-smokers(adjust OR =0.448,95%CI 0.208～0.967,p=0.041), not the tagSNPs rs7208693 of MPO. The all 4 Haplotype-tagging SNPs, rs1695, rs4891, rs762803 and rs749174, showed association with lung cancer susceptibility in the smokers. Phase 2 sofrware was used to reconsrtuct the haplotype for GSTP1, and the haplotype(CACA) showed an increased risk of lung cancer among the smokers(adjust OR=1.53,95% CI 1.04～2.25,p=0.033). Furthermore, the diplotype analyses also demonstrated the significant association beween the risk haplotype and lung cancer. The risk haplotypes cosegregate with one or more biologically functional polymorphisms and it corresponds to a recessive inheritance mode. The results of Meta analysis indicate that the polymorphisms of MPO G-463A and GSTP1 rs1695 were not significantly associated with lung cancer risk. We cloned and sequenced the sequence of CYP2A13 gene, and the outcome indicate that the homologous sequences may interfere with the SNP study and some published SNPs in dbSNPs may not exist.
In conclusion, our study firstly investigated the association between the common polymorhpisms of the 3 candidated genes and lung cancer risk according to the SNPs information published. We found a risk SNPs of CYP2A13 and a risk haplotype of GSTP1 ssociated with lung caner, and these polymorphisms may be candidated SNP markers for lung cancer susceptibility in Chinese, which can be defined lung cancer risk SNPs
引文
1 Jemal A, Siegel R, Ward E,et al.Cancer statistics,2009.CA Cancer J Clin,2009,59 (4):225-249
2 张思维,陈万青,雷正龙等.中国肿瘤登记处2004年恶性肿瘤发病资料分析.中国肿瘤,2008,17(11)：909-912
3 朱文,周清华.肺癌的遗传易感性和环境致癌.中国肺癌杂志,2003,6(6)：430-433
4 陈琛,万海粟,周清华.新一代基因测序技术及其在肿瘤研究中的应用.中国肺癌杂志,2010,13(2)：154-160
5 Phillips COnline resources for SNP analysis:a review and route map.Mol Biotechnol,2007,35 (1):65-97
6 Munteanu I, Didilescu C [Chemistry and toxicology of cigarette smoke in the lungs].Pneumologia,2007,56 (1):41,43-4,146
7 West KA, Brognard J, Clark AS,et al.Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells.J Clin Invest,2003,111 (1):81-90
8 Chobanyan NS, Nersesyan AKRe:metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke.J Natl Cancer Inst,2001,93 (20):1575-1577
9 Habdous M, Siest G, Herbeth B,et al.Glutathione S-transferases genetic polymorphisms and human diseases:overview of epidemiological studies.Ann Biol Clin (Paris),2004,62 (1):15-24
10 Timofeeva MN, Kropp S, Sauter W, et al. CYP450 polymorphisms as risk factors for early-onset lung cancer:gender-specific differences.Carcinogenesis, 2009,30 (7):1161-1169
11 李代蓉,周清华.CYP450和GST基因多态性与肿瘤易感性研究进展.中国肺癌杂志,2003,6(2)：158-162
12 Chen D, Tian T, Wang H,et al. Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population.Pharmacogenet Genomics,2009,19 (1):25-34
13王林,吴逸明.GSTP1与肿瘤关系的研究进展.国外医学卫生学分册,2006,33(5)：300-303
14 Constantin D, Mehrotra K, Rahimtula A,et al. Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes.Environ Health Perspect,1994,102 Suppl 4:161-164
15 Gilliland FD, Harms HJ, Crowell RE,et al.Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are associated with aberrant promoter methylation of P16(INK4a) and O(6)-methylguanine-DNA methyltransferase in sputum. Cancer Res,2002,62 (8):2248-2252
16 Perera FP, Mooney LA, Stampfer M,et al. Associations between carcinogen-DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians'Health Cohort Study. Carcinogenesis,2002, 23 (10):1641-1646
17 Cote ML, Chen W, Smith DW,et al.Meta-and pooled analysis of GSTP1 polymorphism and lung cancer:a HuGE-GSEC review.Am J Epidemiol,2009, 169 (7):802-814
18 Knaapen AM, Gungor N, Schins RP,et al. Neutrophils and respiratory tract DNA damage and mutagenesis:a review.Mutagenesis,2006,21 (4):225-236
19 Gungor N, Knaapen AM, Munnia A,et al.Genotoxic effects of neutrophils and hypochlorous acid.Mutagenesis,2009,1-6
20 Gungor N, Godschalk RW, Pachen DM,et al.Activated neutrophils inhibit nucleotide excision repair in human pulmonary epithelial cells:role of myeloperoxidase.FASEB J,2007,21 (10):2359-2367
21 Cascorbi IGenetic basis of toxic reactions to drugs and chemicals.Toxicol Lett, 2006,162 (1):16-28
22 Petruska JM, Mosebrook DR, Jakab GJ,et al.Myeloperoxidase-enhanced formation of (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene-DNA adducts in lung tissue in vitro:a role of pulmonary inflammation in the bioactivation of a procarcinogen. Carcinogenesis,1992,13 (7):1075-1081
23 Chan EC, Lam SY, Fu KH,et al.Polymorphisms of the GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes in Chinese patients with non-small cell lung cancers: relationship with aberrant promoter methylation of the CDKN2A and RARB genes.Cancer Genet Cytogenet,2005,162 (1):10-20
24 Taioli E, Benhamou S, Bouchardy C,et al.Myeloperoxidase G-463A polymorphism and lung cancer:a HuGE genetic susceptibility to environmental carcinogens pooled analysis.Genet Med,2007,9 (2):67-73
25 Feyler A, Voho A, Bouchardy C,et al.Point:myeloperoxidase-463G--> a polymorphism and lung cancer risk.Cancer Epidemiol Biomarkers Prev,2002,11 (12):1550-1554
26 Kiyohara C, Yoshimasu K, Takayama K,et al.NQO1, MPO, and the risk of lung cancer:a HuGE review.Genet Med,2005,7 (7):463-478
27 Zhu LR, Thomas PE, Lu G,et al.CYP2A13 in human respiratory tissues and lung cancers:an immunohistochemical study with a new peptide-specific antibody.Drug Metab Dispos,2006,34 (10):1672-1676
28 Zhang X, D'Agostino J, Wu H,et al.CYP2A13:variable expression and role in human lung microsomal metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.J Pharmacol Exp Ther,2007, 323 (2):570-578
29 Wang H, Tan W, Hao B,et al.Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK.Cancer Res,2003,63 (22):8057-8061
30 Su T, Bao Z, Zhang QY,et al.Human cytochrome P450 CYP2A13:predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen,4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res,2000,60 (18):5074-5079
31 He XY, Tang L, Wang SL,et al.Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract.Int J Cancer,2006,118 (11):2665-2671
32 Cauffiez C, Lo-Guidice JM, Quaranta S,et al.Genetic polymorphism of the human cytochrome CYP2A13 in a French population:implication in lung cancer susceptibility.Biochem Biophys Res Commun,2004,317 (2):662-669
33 D'Agostino J, Zhang X, Wu H,et al.Characterization of CYP2A13*2, a variant cytochrome P450 allele previously found to be associated with decreased incidences of lung adenocarcinoma in smokers.Drug Metab Dispos,2008,36 (11):2316-2323
34 Shah PP, Singh AP, Singh M,et al.Association of functionally important polymorphisms in cytochrome P4501B1 with lung cancer.Mutat Res,2008,643 (1-2):4-10
35石云,周宜开,任恕.生物转化酶类基因多态性与肿瘤易感性.国外医学分子生物学分册,2001,23(5)：267-269
36靳光付,苗瑞芬,路滟等.谷胱甘肽转移酶M1基因多态与胃癌易感性关系的Meta分析.中国肿瘤,2007,16(12)：970-974
37苗瑞芳,邓一枚,陈文森等.细胞色素P4502E1(CYP2E1)基因多态性与胃癌易感性的Meta分析.中国肿瘤,2007,16(12)：966-969
38 Villard PH, Seree E, Lacarelle B,et al.Effect of cigarette smoke on hepatic and pulmonary cytochromes P450 in mouse:evidence for CYP2E1 induction in lung.Biochem Biophys Res Commun,1994,202 (3):1731-1737
39 Ariyoshi N, Miyamoto M, Umetsu Y,et al.Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers.Cancer Epidemiol Biomarkers Prev,2002,11 (9):890-894
40 Shaffi SM, Shah MA, Bhat IA,et al.CYP1A1 polymorphisms and risk of lung cancer in the ethnic Kashmiri population.Asian Pac J Cancer Prev,2009,10 (4): 651-656
41 Crosbie PA, Barber PV, Harrison KL,et al.GSTM1 copy number and lung cancer risk.Mutat Res,2009,664 (1-2):1-5
42 Lam TK, Ruczinski I, Helzlsouer K,et al.Copy number variants of GSTM1 and GSTT1 in relation to lung cancer risk in a prospective cohort study.Ann Epidemiol,2009,19 (8):546-552
43 Kumar M, Agarwal SK, Goel SKLung cancer risk in north Indian population: role of genetic polymorphisms and smoking.Mol Cell Biochem,2009,322 (1-2): 73-79
44 Lee KM, Kang D, Clapper ML,et al.CYP1A1, GSTM1, and GSTT1 polymorphisms, smoking, and lung cancer risk in a pooled analysis among Asian populations.Cancer Epidemiol Biomarkers Prev,2008,17 (5):1120-1126
45 Sobti RC, Kaur P, Kaur S,et al.Combined effect of GSTM1, GSTT1 and GSTP1 polymorphisms on histological subtypes of lung cancer.Biomarkers,2008,13 (3):282-295
46 Sobti RC, Kaur P, Kaur S,et al. Impact of interaction of polymorphic forms of p53 codon 72 and N-acetylation gene (NAT2) on the risk of lung cancer in the North Indian population.DNA Cell Biol,2009,28(9):443-449
47 Lee CN, Yu MC, Bai KJ,et al.NAT2 fast acetylator genotypes are associated with an increased risk for lung cancer with wildtype epidermal growth factor receptors in Taiwan.Lung Cancer,2009,64 (1):9-12
48 McKay JD, Hashibe M, Hung RJ,et al.Sequence variants of NAT1 and NAT2 and other xenometabolic genes and risk of lung and aerodigestive tract cancers in Central Europe.Cancer Epidemiol Biomarkers Prev,2008,17 (1):141-147
49 Kiyohara C, Yoshimasu K, Takayama K, et al. EPHX1 polymorphisms and the risk of lung cancer:a HuGE review. Epidemiology,2006,17 (1):89-99
50 Voho A, Metsola K, Anttila S, et al. EPHX1 gene polymorphisms and individual susceptibility to lung cancer.Cancer Lett,2006,237 (1):102-108
51 Finckh C, Atalla A, Nagel G,et al.Expression and NNK reducing activities of carbonyl reductase and 11beta-hydroxysteroid dehydrogenase type 1 in human lung.Chem Biol Interact,2001,130-132 (1-3):761-773
52 Bear WL, Teel RWEffects of citrus phytochemicals on liver and lung cytochrome P450 activity and on the in vitro metabolism of the tobacco-specific nitrosamine NNK.Anticancer Res,2000,20 (5A):3323-3329
53 Witschi H, Espiritu I, Peake JL, et al. The carcinogenicity of environmental tobacco smoke. Carcinogenesis,1997,18 (3):575-586
54 Jorquera R, Castonguay A, Schuller HM. Effect of tobacco smoke condensate on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by adult and fetal hamster microsomes. Drug Metab Dispos,1993,21 (2):318-324
55 陆宏,李燕.细胞色素P450与肿瘤.生理科学进展,1997,28(2)：178-180
56 von Weymarn LB, Chun JA, Hollenberg PF. Effects of benzyl and phenethyl isothiocyanate on P450s 2A6 and 2A13:potential for chemoprevention in smokers. Carcinogenesis,2006,27 (4):782-790
57 Xin-Yuan Cheng, Guo-Lin Chen, Wei-Xia Zhang, et,al. Arg257Cys polymorphism of CYP2A13 in a Chinese population.Clinica Chimica Acta,2004, 34(3):213-216
58 Zhang X, Chen Y, Liu Y, et al.Single nucleotide polymorphisms of the human cyp2al3 gene:evidence for a null allele.Drug Metab Dispos,2003,31 (9): 1081-1085
59 Cauffiez C, Pottier N, Tournel G, et al. CYP2A13 genetic polymorphism in French Caucasian, Gabonese and Tunisian populations.Xenobiotica,2005,35 (7):661-669
60 Paschke T, Riefler M, Schuler-Metz A, et al.Comparison of cytochrome P450 2A6 polymorphism frequencies in Caucasians and African-Americans using a new one-step PCR-RFLP genotyping method.Toxicology,2001,168 (3): 259-268
61 Smith BD, Sanders JL, Porubsky PR, et al. Structure of the human lung cytochrome P450 2A13. J Biol Chem,2007,282 (23):17306-17313
62王瑾,许峰,周清华.肺癌流行病学研究进展.中国肺癌杂志,2005,8(5)：395-399
63 Spivack SD, Hurteau GJ, Fasco MJ,et al.Phase Ⅰ and Ⅱ carcinogen metabolism gene expression in human lung tissue and tumors.Clin Cancer Res,2003,9(16 Pt1):6002-6011
64 Kiyohara C, Ohno Y.Role of metabolic polymorphisms in lung carcinogenesis.Nippon Koshu Eisei Zasshi,1999,46 (4):241-249
65 Sundberg K, Johansson AS, Stenberg G,et al.Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons. Carcinogenesis, 1998,19 (3):433-6
66 Wiencke JKDNA adduct burden and tobacco carcinogenesis.Oncogene,2002,21 (48):7376-91
67 Ryberg D, Skaug V, Hewer A,et al.Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis,1997,18 (7):1285-1289
68 Ritchie KJ, Henderson CJ, Wang XJ,et al.Glutathione transferase pi plays a critical role in the development of lung carcinogenesis following exposure to tobacco-related carcinogens and urethane.Cancer Res,2007,67 (19):9248-9257
69 Schoket B, Papp G, Levay K,et al.Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure.Mutat Res,2001,482 (1-2):57-69
70 Hu X, Ji X, Srivastava SK,et al.Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene.Arch Biochem Biophys,1997,345 (1):32-38
71 Aldrich MC, Selvin S, Hansen HM,et al.CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification.Cancer Res,2009,69 (6):2340-8
72 Gallagher CJ, Ahn K, Knipe AL,et al. Association between haplotypes of manganese superoxide dismutase (SOD2), smoking, and lung cancer risk.Free Radic Biol Med,2009,46 (1):20-24
73 Yin J, Vogel U, Ma Y,et al.Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population.Mutat Res,2008,641 (1-2):12-18
74黄萌,蔡琳.Haploview与PHASE在单体型研究中的应用.福建医科大学学报,2009,43(4)：310-313
75 Ye Z, Song H, Higgins JP,et al.Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls:meta-analysis of 130 studies.PLoS Med,2006,3 (4):e91
76 Knaapen AM, Schins RP, Polat D,et al.Mechanisms of neutrophil-induced DNA damage in respiratory tract epithelial cells.Mol Cell Biochem,2002,234-235 (1-2):143-51
77 Arlt VM, Schmeiser HH, Osborne MR,et al.Identification of three major DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in rat lung at the C8 and N2 position of guanine and at the N6 position of adenine.Int J Cancer,2006,118 (9):2139-2146
78 Austin GE, Lam L, Zaki SR,et al.Sequence comparison of putative regulatory DNA of the 5'flanking region of the myeloperoxidase gene in normal and leukemic bone marrow cells.Leukemia,1993,7 (9):1445-50
79 London SJ, Lehman TA, Taylor JAMyeloperoxidase genetic polymorphism and lung cancer risk.Cancer Res,1997,57 (22):5001-5013
80吴晓明,周宜开,任恕.髓过氧化物酶基因多态性与肺癌遗传易感性的研究.癌症,2003,22(9)：912-915
81 吕文富,齐军,邢德印.髓过氧化物酶基因G-463A多态与中国人肺癌遗传易感性.中华肿瘤杂志,2002,24(3)：250-253
82张体艳,洪锡田,吴拥军.河南汉族肺癌患者髓过氧化物酶基因多态性分析.郑州大学学报,2007,42(3)：448-449
83 Hoy A, Leininger-Muller B, Kutter D,et al.Growing significance of myeloperoxidase in non-infectious diseases.Clin Chem Lab Med,2002,40 (1): 2-8
84 Dabrowska M, Prokopowicz J, Pietruczuk M,et al.The activity of neutrophil myeloperoxidase in patients with lung carcinoma.Folia Haematol Int Mag Klin Morphol Blutforsch,1988,115 (5):613-9
85 Gresner P, Gromadzinska J, Wasowicz WPolymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer.Lung Cancer,2007,57 (1):1-25
86 Mihi Yang, Yunhee Choi, Bin HwangboCombined effects of genetic polymorphisms in six selected genes on lung cancer susceptibility, lung cancer,2007,5(7):135-142
87 Park JH, Park JM, Kim EJ,et al.Myeloperoxidase-463G>A polymorphism and risk of primary lung cancer in a Korean population.Cancer Detect Prev,2006,30 (3):257-61
88 Loc Le Marchand,Ann Seifried, Annette LumAssociation of the Myeloperoxidase-463G-A Polymorphism with lung cancer risk.Cancer Epidemiology, Biomarkers & Prevention,2000,9:181-184
89 Cascorbi I, Henning S, Brockmoller J,et al.Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant--463A of the myeloperoxidase gene.Cancer Res,2000,60 (3)-:644-649
90 Li-Lian Xu, Geoffrey Liu,David P. Miller, Wei ZhouCounterpoint The MyeloperoxidaseA Polymorphism Does Not.Cancer Epidemiology, Biomarkers & Prevention,2002,11:1555-1559
91 Dally H, Gassner K, Jager B,et al.Myeloperoxidase (MPO) genotype and lung cancer histologic types:the MPO-463 A allele is associated with reduced risk for small cell lung cancer in smokers.Int J Cancer,2002,102 (5):530-535
92 ORHUN H. KANTARCI, TIMOTHY G. LESNICK,PING YANG.. Myeloperoxidase Polymorphism Associated.Mayo Clin Proc,2002,77:17-22
93 Jill Everland Larsen,Maree Louise Colosimo,Ian Anthony YangCYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung.Carcinogenesis,2006,27 (3):525-532
94 Schabath MB, Spitz MR, Hong WK,et al.A myeloperoxidase polymorphism associated with reduced risk of lung cancer.Lung Cancer,2002,37 (1):35-40
95 Nohelia Cajas-Salazar, Carlos H. Sierra-Torres, Salama ACombined effect of MPO GSTM1 and GSTT1 polymorphisms on chromosome aberrations and lung cancer risk.international journal of hygene and enviromental health,2003,20 (6):473-483
96 Liu G, Zhou W, Wang LI,et al.MPO and SOD2 polymorphisms, gender, and the risk of non-small cell lung carcinoma.Cancer Lett,2004,214 (1):69-79
97 Chevrier I, Stucker I, Houllier AM,et al.Myeloperoxidase:new polymorphisms and relation with lung cancer risk.Pharmacogenetics,2003,13 (12):729-39
98 Misra RR, Tangrea JA, Virtamo J,et al.Variation in the promoter region of the myeloperoxidase gene is not directly related to lung cancer risk among male smokers in Finland.Cancer Lett,2001,164 (2):161-167
99 Zienolddiny S, Campa D, Lind H,et al.A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers.Carcinogenesis,2008,29 (6):1164-1169
100 Yoon KA, Kim JH, Gil HJ,et al.CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women.Lung Cancer,2008,60 (1):40-6
101 Van Schooten FJ, Boots AW, Knaapen AM,et al.Myeloperoxidase (MPO)-463G->A reduces MPO activity and DNA adduct levels in bronchoalveolar lavages of smokers.Cancer Epidemiol Biomarkers Prev,2004,13 (5):828-833
102 Kantarci OH, Lesnick TG, Yang P,et al.Myeloperoxidase-463 (G-->A) polymorphism associated with lower risk of lung cancer.Mayo Clin Proc,2002,77 (1):17-22
1 Jemal A, Siegel R, Ward E,et al.Cancer statistics,2009.CA Cancer J Clin,2009, 59 (4):225-249
2 张思维,陈万青,雷正龙等.中国肿瘤登记处2004年恶性肿瘤发病资料分析.中国肿瘤,2008,17(11)：909-912
3 Ferlay J, Autier P, Boniol M,et al.Estimates of the cancer incidence and mortality in Europe in 2006.Ann Oncol,2007,18 (3):581-592
4 Taylor JG, Choi EH, Foster CB,et al.Using genetic variation to study human disease.Trends Mol Med,2001,7 (11):507-512
5 The International HapMap ConsortiumThe International HapMap Project. NATURE,2003,42(6):789-796
6 Gu HF. Single nucleotide polymorphisms(SNPs)and SNP databases. Zhonghua YiXue Yi Chuan Xue Za Zhi,2001,18 (6):479-481
7 Phillips COnline resources for SNP analysis:a review and route map.Mol Biotechnol,2007,35 (1):65-97
8 Dogan I, Onen HI, Yurdakul AS,et al. Polymorphisms in the vitamin D receptor gene and risk of lung cancer.Med Sci Monit,2009,15 (8):BR232-242
9 Rotunno M, Yu K, Lubin JH,et al. Phase I metabolic genes and risk of lung cancer:multiple polymorphisms and mRNA expression. PLoS One,2009,4(5): e5652
10 Landvik NE, Hart K, Skaug V,et al.A specific interleukin-1B haplotype correlates with high levels of IL1B mRNA in the lung and increased risk of non-small cell lung cancer.Carcinogenesis,2009,30 (7):1186-1192
11 Wu W, Zhang W, Qiao R,et al.Association of XPD polymorphisms with severe toxicity in non-small cell lung cancer patients in a Chinese population.Clin Cancer Res,2009,15 (11):3889-3895
12 Yoon KA, Kim JH, Gil HJ,et al.CYPlBl, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women.Lung Cancer,2008,60 (1):40-46
13 Mihi Yang, Yunhee Choi, Bin HwangboCombined effects of genetic polymor-phisms in six selected genes on lung cancer susceptibility.lung cancer,2007,5 (7):135-142
14 Jill Everland Larsen,Maree Louise Colosimo,Ian Anthony YangCYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung. Carcinogenesis,2006,27 (3):525-532
15陈琛,万海粟,周清华.新一代基因测序技术及其在肿瘤研究中的应用.中国肺癌杂志,2010,13(2)：154-160
16 Liu Y, Liu P, Wen W,et al.Haplotype and cell proliferation analyses of candidate lung cancer susceptibility genes on chromosome 15q24-25.1.Cancer Res,2009,69 (19):7844-7850
17 Sun T, Gao Y, Tan W,et al.Haplotypes in matrix metalloproteinase gene cluster on chromosome 11q22 contribute to the risk of lung cancer development and progression.Clin Cancer Res,2006,12 (23):7009-7017
18 Yin J, Vogel U, Ma Y,et al.Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population.Mutat Res,2008,641 (1-2):12-18
19 Amos CI, Wu X, Broderick P,et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.Nat Genet,2008,40 (5):616-622
20 You M, Wang D, Liu P,et al.Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene.Clin Cancer Res,2009,15 (8):2666-2674
21 朱文,周清华.肺癌的遗传易感性和环境致癌.中国肺癌杂志,2003,6(6)：430-433
22谷俊东,滑峰,周清华等.肺癌家族聚集性的系统评价.中国肺癌杂志,2010,13(3)： 224-229
23 Constantin D, Mehrotra K, Rahimtula A,et al. Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes.Environ Health Perspect,1994,102 Suppl 4:161-164
24 Hu X, Ji X, Srivastava SK,et al.Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene.Arch Biochem Biophys,1997,345 (1):32-38
25 Petruska JM, Mosebrook DR, Jakab GJ,et al.Myeloperoxidase-enhanced formation of (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene-DNA adducts in lung tissue in vitro:a role of pulmonary inflammation in the bioactivation of a procarcinogen.Carcinogenesis,1992,13 (7):1075-1081
26 Bear WL, Teel RWEffects of citrus phytochemicals on liver and lung cyto-chrome P450 activity and on the in vitro metabolism of the tobacco-specific nitrosamine NNK.Anticancer Res,2000,20 (5A):3323-3329
27 Hirvonen A, Husgafvel-Pursiainen K, Anttila S,et al.Metabolic cytochrome P450 genotypes and assessment of individual susceptibility to lung cancer. Phar-macogenetics,1992,2 (6):259-263
28陆宏,李燕.细胞色素P450与肿瘤.生理科学进展,1997,28(2)：178-180
29 Shah PP, Singh AP, Singh M,et al.Association of functionally important poly-morphisms in cytochrome P4501B1 with lung cancer. Mutat Res,2008,643 (1-2):4-10
30石云,周宜开,任恕.生物转化酶类基因多态性与肿瘤易感性.国外医学分子生物学分册,2001,235：267-269
31 靳光付,苗瑞芬,路滟等.谷胱甘肽转移酶M1基因多态与胃癌易感性关系的Meta分析.中国肿瘤,2007,16(12)：970-974
32苗瑞芳,邓一枚,陈文森等.细胞色素P450 2E1(CYP2E1)基因多态性与胃癌易感性的Meta分析.中国肿瘤,2007,16(12)：966-969
33 Wang H, Tan W, Hao B,et al.Substantial reduction in risk of lung adeno-carcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK.Cancer Res,2003,63 (22):8057-8061
34 Cauffiez C, Lo-Guidice JM, Quaranta S,et al.Genetic polymorphism of the human cytochrome CYP2A13 in a French population:implication in lung cancer susceptibility.Biochem Biophys Res Commun,2004,317 (2):662-669
35 D'Agostino J, Zhang X, Wu H,et al.Characterization of CYP2A13*2, a variant cytochrome P450 allele previously found to be associated with decreased incidences of lung adenocarcinoma in smokers. Drug Metab Dispos,2008,36 (11):2316-2323
36夏英,张翠兰.CYP450和GST基因多态性与肿瘤易感性研究进展.中华放射医学与防护杂志,2003,235：385-386
37 Lewis SJ, Cherry NM, Niven RM,et al.GSTMl, GSTT1 and GSTP1 poly-morphisms and lung cancer risk.Cancer Lett,2002,180 (2):165-171
38 Cote ML, Chen W, Smith DW,et al.Meta-and pooled analysis of GSTP1 polymorphism and lung cancer:a HuGE-GSEC review.Am J Epidemiol,2009, 169 (7):802-814
39张徐军,闵捷.谷胱甘肽S-转移酶M1、T1基因多态性与儿童急性白血病遗传易感性的Meta分析.环境与健康杂志,2006,23(5)：424-426
40 Habdous M, Siest G, Herbeth B,et al.Glutathione S-transferases genetic polymorphisms and human diseases:overview of epidemiological studies.Ann Biol Clin (Paris),2004,62 (1):15-24
41 Habalova V, Salagovic J, Kalina I,et al.A pilot study testing the genetic poly-morphism of N-acetyltransferase 2 as a risk factor in lung cancer. Neoplasma, 2005,52 (5):364-368
42 Chiou HL, Wu MF, Chien WP,et al.NAT2 fast acetylator genotype is associated with an increased risk of lung cancer among never-smoking women in Taiwan. Cancer Lett,2005,223 (1):93-101
43 Kiyohara C, Yoshimasu K, Takayama K,et al.EPHX1 polymorphisms and the risk of lung cancer:a HuGE review.Epidemiology,2006,17 (1):89-99
44 Chen D, Tian T, Wang H,et al. Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population.Pharmacogenet Genomics,2009,19 (1):25-34
45 Kohno T, Kunitoh H, Suzuki K,et al.Association of KRAS polymorphisms with risk for lung adenocarcinoma accompanied by atypical adenomatous hyper-plasias.Carcinogenesis,2008,29 (5):957-963
46 Chin LJ, Ratner E, Leng S,et al.A SNP in a let-7 microRNA complementary site in the KRAS 3'untranslated region increases non-small cell lung cancer risk. Cancer Res,2008,68 (20):8535-8540
47 Zhang X, Miao X, Guo Y,et al. Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer.Hum Mutat,2006,27 (1):110-117
48 Mechanic LE, Bowman ED, Welsh JA,et al.Common genetic variation in TP53 is associated with lung cancer risk and prognosis in African Americans and somatic mutations in lung tumors.Cancer Epidemiol Biomarkers Prev,2007,16 (2):214-222
49 Choi YY, Kang HK, Choi JE,et al. Comprehensive assessment of P21 poly-morphisms and lung cancer risk.J Hum Genet,2008,53 (1):87-95
50胡志斌,缪小平,马红霞.肺癌易感性与p73基因多态性关系的研究.中华流行病学杂志,2005,262：106-108
51 Sung JS, Han SG, Whang YM,et al.Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer.Lung Cancer, 2008,61 (3):301-308
52 Chen D, Jin G, Wang Y,et al.Genetic variants in peroxisome proliferator-activated receptor-gamma gene are associated with risk of lung cancer in a Chinese population.Carcinogenesis,2008,29 (2):342-350
53 Kim JS, Yim SV, Koh IS,et al.Single-nucleotide polymorphisms (SNPs) and haplotype analysis in vascular endothelial growth factor (VEGF) gene in the patients with Parkinson disease and lung cancer.Arch Gerontol Geriatr,2009,48 (3):287-290
54 Zhai R, Liu G, Zhou W,et al.Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non-small cell lung cancer.Clin Cancer Res, 2008,14 (2):612-617
55 Jo UH, Han SG, Seo JH,et al.The genetic polymorphisms of HER-2 and the risk of lung cancer in a Korean population.BMC Cancer,2008,8:359
56 Su L, Zhou W, Asomaning K,et al.Genotypes and haplotypes of matrix metalloproteinase 1,3 and 12 genes and the risk of lung cancer. Carcinogenesis, 2006,27 (5):1024-1029
57 Sauter W, Rosenberger A, Beckmann L,et al.Matrix metalloproteinase 1 (MMP1) is associated with early-onset lung cancer.Cancer Epidemiol Biomarkers Prev,2008,17 (5):1127-1135
58 Lee WK, Kim JS, Kang HG,et al.Polymorphisms in the Caspase7 gene and the risk of lung cancer.Lung Cancer,2009,65 (1):19-24
59 Jang JS, Kim KM, Choi JE,et al.Identification of polymorphisms in the Caspase-3 gene and their association with lung cancer risk.Mol Carcinog,2008,47 (5): 383-390
60 Son JW, Kang HK, Chae MH,et al.Polymorphisms in the caspase-8 gene and the risk of lung cancer. Cancer Genet Cytogenet,2006,169 (2):121-127
61 Park JY, Park JM, Jang JS,et al.Caspase 9 promoter polymorphisms and risk of primary lung cancer. Hum Mol Genet,2006,15 (12):1963-1971
62 Shin S, Sung B J, Cho YS,et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7.Biochemistry,2001,40 (4):1117-1123
63 Suzuki A, Ito T, Kawano H,et al.Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene,2000,19 (10):1346-1353
64 Jang JS, Kim KM, Kang KH,et al.Polymorphisms in the survivin gene and the risk of lung cancer.Lung Cancer,2008,60 (1):31-39
65 Hu Z, Wang H, Shao M,et al.Genetic variants in MGMT and risk of lung cancer in Southeastern Chinese:a haplotype-based analysis.Hum Mutat,2007,28 (5): 431-440
66 Yin J, Vogel U, Ma Y,et al.HapMap-based study of the DNA repair gene ERCC2 and lung cancer susceptibility in a Chinese population. Carcinogenesis, 2009,30 (7):1181-1185
67 Cote ML, Yoo W, Wenzlaff AS,et al.Tobacco and estrogen metabolic poly-morphisms and risk of non-small cell lung cancer in women. Carcinogenesis, 2009,30 (4):626-635
68 Ma H, Xu L, Yuan J,et al.Tagging single nucleotide polymorphisms in excision repair cross-complementing group 1 (ERCC1) and risk of primary lung cancer in a Chinese population. Pharmacogenet Genomics,2007,17 (6):417-423
69 Yin J, Vogel U, Ma Y,et al. A haplotype encompassing the variant allele of DNA repair gene polymorphism ERCC2/XPD Lys751Gln but not the variant allele of Asp312Asn is associated with risk of lung cancer in a northeastern Chinese population.Cancer Genet Cytogenet,2007,175 (1):47-51
70 Kiyohara C, Yoshimasu KGenetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk:a meta-analysis.Int J Med Sci,2007,4 (2): 59-71
71 Tseng RC, Hsieh FJ, Shih CM,et al.Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes:a multiple genotype-phenotype study. Cancer,2009,115(13):2939-2948
72 Ma H, Hu Z, Wang H,et al.ERCC6/CSB gene polymorphisms and lung cancer risk.Cancer Lett,2009,273 (1):172-176
73 Chang CH, Hsiao CF, Chang GC,et al.Interactive effect of cigarette smoking with human 8-oxoguanine DNA N-glycosylase 1 (hOGGl) polymorphisms on the risk of lung cancer:a case-control study in Taiwan. Am J Epidemiol,2009, 170 (6):695-702
74 Okasaka T, Matsuo K, Suzuki T,et al.hOGG1 Ser326Cys polymorphism and risk oflung cancer by histological type. J Hum Genet,2009,54 (12):739-745
75 Li H, Hao X, Zhang W,et al. The hOGG1 Ser326Cys polymorphism and lung cancer risk:a meta-analysis. Cancer Epidemiol Biomarkers Prev,2008,17 (7): 1739-1745
76 Lee YC, Morgenstern H, Greenland S,et al.A case-control study of the association of the polymorphisms and haplotypes of DNA ligase I with lung and upper-aerodigestive-tract cancers. Int J Cancer,2008,122 (7):1630-1638
77 Danoy P, Michiels S, Dessen P,et al.Variants in DNA double-strand break repair and DNA damage-response genes and susceptibility to lung and head and neck cancers.Int J Cancer,2008,123 (2):457-463
78 Engels EA, Wu X, Gu J,et al. Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer.Cancer Res,2007,67 (13): 6520-6527
79 Gervasini G, Carrillo JA, Garcia M,et al.Adenosine triphosphate-binding cassette Bl (ABCB1) (multidrug resistance 1) G2677T/A gene polymorphism is associated with high risk of lung cancer. Cancer,2006,107 (12):2850-2857
80 Gu J, Gong Y, Huang M,et al.Polymorphisms of STK15 (Aurora-A) gene and lung cancer risk in Caucasians.Carcinogenesis,2007,28 (2):350-355
81 Kim JH, Kim H, Lee KY,et al.Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. Hum Mol Genet,2006,15 (7):1181-1186
82 Wang H, Hao B, Chen X,et al.Beta-2 adrenergic receptor gene (ADRB2) polymorphism and risk for lung adenocarcinoma:a case-control study in a Chinese population.Cancer Lett,2006,240 (2):297-305
83 Kang HG, Chae MH, Park JM,et al.Polymorphisms in TGF-betal gene and the risk of lung cancer.Lung Cancer,2006,52 (1):1-7
84 Lee SJ, Jeon HS, Jang JS,et al.DNMT3B polymorphisms and risk of primary lung cancer.Carcinogenesis,2005,26 (2):403-409
85 俞晓静,陈坤,金明娟.5,10-亚甲基四氢叶酸还原酶基因多态性与结直肠癌易感性关系的Meta分析.中国慢性病预防与控制,2006,14(2)：115-118
86 Liu CS, Tsai CW, Hsia TC,et al.Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients.Cancer Genomics Proteomics,2009,6 (6):325-329
87 Boccia S, Boffetta P, Brennan P,et al.Meta-analyses of the methylenetetra-hydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer.Cancer Lett,2009,273 (1):55-61
88 陈文森,靳光付,邓一枚.IGF1和IGFBP3多态性与乳腺癌易感性的Meta分析.中国肿瘤,2007,16(12)：975-978
89 Nacak M, Nacak I, Sanli M,et al.Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey.Cancer Genet Cytogenet,2010,198 (1):22-26
90 Mita Y, Yasuda Y, Sakai A,et al.Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers. J Cancer Res Clin Oncol,2010,136 (2):249-259
91 Agachan B, Kucukhuseyin O, Aksoy P,et al.Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking. Anticancer Res,2009,29 (6):2417-2420
92 Lo YL, Jou YS, Hsiao CF,et al.A polymorphism in the APE1 gene promoter is associated with lung cancer risk.Cancer Epidemiol Biomarkers Prev,2009,18 (1):223-229
93 Arslan S, Silig Y, Pinarbasi HAn investigation of the relationship between SULT1A1 Arg(213)His polymorphism and lung cancer susceptibility in a Turkish population.Cell Biochem Funct,2009,27 (4):211-215
94 Miao R, Gu H, Liu H,et al.Tagging single nucleotide polymorphisms in MBD4 are associated with risk of lung cancer in a Chinese population.Lung Cancer, 2008,62 (3):281-286
95 Bernig T, Chanock SJChallenges of SNP genotyping and genetic variation:its future role in diagnosis and treatment of cancer.Expert Rev Mol Diagn,2006,6 (3):319-331
96 Wang Y, Armstrong SAGenome-wide SNP analysis in cancer:leukemia shows the way.Cancer Cell,2007,11 (4):308-309
97 Craig DW, Stephan DAApplications of whole-genome high-density SNP genotyping. Expert Rev Mol Diagn,2005,5 (2):159-170
98 Wang Y, Broderick P, Matakidou A,et al.Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers.Carcinogenesis,2010,31 (2):234-238
99 Zienolddiny S, Skaug V, Landvik NE,et al.The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung. Carcinogenesis,2009,30 (8):1368-1371
100 Falvella FS, Galvan A, Frullanti E,et al.Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk.Clin Cancer Res,2009,15 (5):1837-1842
101 Inoue I. SNP database and establishment of personalized medicine..Nippon Yakurigaku Zasshi,2002,120 (1):41-42
102 Iida A, Saito S, Sekine A,et al. SNP collection, pharmacogenomics, and the future of drug therapy.Gan To Kagaku Ryoho,2002,29 (9):1665-1673
103 Sohn JW, Lee SY, Lee SJ,et al. MDR1 polymorphisms predict the response to etoposide-cisplatin combination chemotherapy in small cell lung cancer.Jpn J Clin Oncol,2006,36 (3):137-141
104 Han JY, Lim HS, Shin ES,et al.Influence of the organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphisms on irinotecan-pharmacokinetics and clinical outcome of patients with advanced non-small cell lung cancer.Lung Cancer,2008,59 (1):69-75
105 Liu G, Gurubhagavatula S, Zhou W,et al.Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib.Pharmacogenomics J,2008,8 (2):129-138
106 Heist RS, Zhou W, Wang Z,et al.Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer.J Clin Oncol,2008,26 (34):5596-5602
107 Kim HT, Lee JE, Shin ES,et al.Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy. J Clin Oncol,2008,26 (36):5972-5979
108 Pine SR, Mechanic LE, Ambs S,et al.Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene.J Natl Cancer Inst,2007,99 (18):1401-1409
109 Yoon SM, Hong YC, Park HJ,et al.The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy.Int J Radiat Oncol Biol Phys,2005,63 (3):885-891
2 张思维,陈万青,雷正龙等.中国肿瘤登记处2004年恶性肿瘤发病资料分析.中国肿瘤,2008,17(11)：909-912
3 朱文,周清华.肺癌的遗传易感性和环境致癌.中国肺癌杂志,2003,6(6)：430-433
4 陈琛,万海粟,周清华.新一代基因测序技术及其在肿瘤研究中的应用.中国肺癌杂志,2010,13(2)：154-160
5 Phillips COnline resources for SNP analysis:a review and route map.Mol Biotechnol,2007,35 (1):65-97
6 Munteanu I, Didilescu C [Chemistry and toxicology of cigarette smoke in the lungs].Pneumologia,2007,56 (1):41,43-4,146
7 West KA, Brognard J, Clark AS,et al.Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells.J Clin Invest,2003,111 (1):81-90
8 Chobanyan NS, Nersesyan AKRe:metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke.J Natl Cancer Inst,2001,93 (20):1575-1577
9 Habdous M, Siest G, Herbeth B,et al.Glutathione S-transferases genetic polymorphisms and human diseases:overview of epidemiological studies.Ann Biol Clin (Paris),2004,62 (1):15-24
10 Timofeeva MN, Kropp S, Sauter W, et al. CYP450 polymorphisms as risk factors for early-onset lung cancer:gender-specific differences.Carcinogenesis, 2009,30 (7):1161-1169
11 李代蓉,周清华.CYP450和GST基因多态性与肿瘤易感性研究进展.中国肺癌杂志,2003,6(2)：158-162
12 Chen D, Tian T, Wang H,et al. Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population.Pharmacogenet Genomics,2009,19 (1):25-34
13王林,吴逸明.GSTP1与肿瘤关系的研究进展.国外医学卫生学分册,2006,33(5)：300-303
14 Constantin D, Mehrotra K, Rahimtula A,et al. Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes.Environ Health Perspect,1994,102 Suppl 4:161-164
15 Gilliland FD, Harms HJ, Crowell RE,et al.Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are associated with aberrant promoter methylation of P16(INK4a) and O(6)-methylguanine-DNA methyltransferase in sputum. Cancer Res,2002,62 (8):2248-2252
16 Perera FP, Mooney LA, Stampfer M,et al. Associations between carcinogen-DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians'Health Cohort Study. Carcinogenesis,2002, 23 (10):1641-1646
17 Cote ML, Chen W, Smith DW,et al.Meta-and pooled analysis of GSTP1 polymorphism and lung cancer:a HuGE-GSEC review.Am J Epidemiol,2009, 169 (7):802-814
18 Knaapen AM, Gungor N, Schins RP,et al. Neutrophils and respiratory tract DNA damage and mutagenesis:a review.Mutagenesis,2006,21 (4):225-236
19 Gungor N, Knaapen AM, Munnia A,et al.Genotoxic effects of neutrophils and hypochlorous acid.Mutagenesis,2009,1-6
20 Gungor N, Godschalk RW, Pachen DM,et al.Activated neutrophils inhibit nucleotide excision repair in human pulmonary epithelial cells:role of myeloperoxidase.FASEB J,2007,21 (10):2359-2367
21 Cascorbi IGenetic basis of toxic reactions to drugs and chemicals.Toxicol Lett, 2006,162 (1):16-28
22 Petruska JM, Mosebrook DR, Jakab GJ,et al.Myeloperoxidase-enhanced formation of (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene-DNA adducts in lung tissue in vitro:a role of pulmonary inflammation in the bioactivation of a procarcinogen. Carcinogenesis,1992,13 (7):1075-1081
23 Chan EC, Lam SY, Fu KH,et al.Polymorphisms of the GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes in Chinese patients with non-small cell lung cancers: relationship with aberrant promoter methylation of the CDKN2A and RARB genes.Cancer Genet Cytogenet,2005,162 (1):10-20
24 Taioli E, Benhamou S, Bouchardy C,et al.Myeloperoxidase G-463A polymorphism and lung cancer:a HuGE genetic susceptibility to environmental carcinogens pooled analysis.Genet Med,2007,9 (2):67-73
25 Feyler A, Voho A, Bouchardy C,et al.Point:myeloperoxidase-463G--> a polymorphism and lung cancer risk.Cancer Epidemiol Biomarkers Prev,2002,11 (12):1550-1554
26 Kiyohara C, Yoshimasu K, Takayama K,et al.NQO1, MPO, and the risk of lung cancer:a HuGE review.Genet Med,2005,7 (7):463-478
27 Zhu LR, Thomas PE, Lu G,et al.CYP2A13 in human respiratory tissues and lung cancers:an immunohistochemical study with a new peptide-specific antibody.Drug Metab Dispos,2006,34 (10):1672-1676
28 Zhang X, D'Agostino J, Wu H,et al.CYP2A13:variable expression and role in human lung microsomal metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.J Pharmacol Exp Ther,2007, 323 (2):570-578
29 Wang H, Tan W, Hao B,et al.Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK.Cancer Res,2003,63 (22):8057-8061
30 Su T, Bao Z, Zhang QY,et al.Human cytochrome P450 CYP2A13:predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen,4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res,2000,60 (18):5074-5079
31 He XY, Tang L, Wang SL,et al.Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract.Int J Cancer,2006,118 (11):2665-2671
32 Cauffiez C, Lo-Guidice JM, Quaranta S,et al.Genetic polymorphism of the human cytochrome CYP2A13 in a French population:implication in lung cancer susceptibility.Biochem Biophys Res Commun,2004,317 (2):662-669
33 D'Agostino J, Zhang X, Wu H,et al.Characterization of CYP2A13*2, a variant cytochrome P450 allele previously found to be associated with decreased incidences of lung adenocarcinoma in smokers.Drug Metab Dispos,2008,36 (11):2316-2323
34 Shah PP, Singh AP, Singh M,et al.Association of functionally important polymorphisms in cytochrome P4501B1 with lung cancer.Mutat Res,2008,643 (1-2):4-10
35石云,周宜开,任恕.生物转化酶类基因多态性与肿瘤易感性.国外医学分子生物学分册,2001,23(5)：267-269
36靳光付,苗瑞芬,路滟等.谷胱甘肽转移酶M1基因多态与胃癌易感性关系的Meta分析.中国肿瘤,2007,16(12)：970-974
37苗瑞芳,邓一枚,陈文森等.细胞色素P4502E1(CYP2E1)基因多态性与胃癌易感性的Meta分析.中国肿瘤,2007,16(12)：966-969
38 Villard PH, Seree E, Lacarelle B,et al.Effect of cigarette smoke on hepatic and pulmonary cytochromes P450 in mouse:evidence for CYP2E1 induction in lung.Biochem Biophys Res Commun,1994,202 (3):1731-1737
39 Ariyoshi N, Miyamoto M, Umetsu Y,et al.Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers.Cancer Epidemiol Biomarkers Prev,2002,11 (9):890-894
40 Shaffi SM, Shah MA, Bhat IA,et al.CYP1A1 polymorphisms and risk of lung cancer in the ethnic Kashmiri population.Asian Pac J Cancer Prev,2009,10 (4): 651-656
41 Crosbie PA, Barber PV, Harrison KL,et al.GSTM1 copy number and lung cancer risk.Mutat Res,2009,664 (1-2):1-5
42 Lam TK, Ruczinski I, Helzlsouer K,et al.Copy number variants of GSTM1 and GSTT1 in relation to lung cancer risk in a prospective cohort study.Ann Epidemiol,2009,19 (8):546-552
43 Kumar M, Agarwal SK, Goel SKLung cancer risk in north Indian population: role of genetic polymorphisms and smoking.Mol Cell Biochem,2009,322 (1-2): 73-79
44 Lee KM, Kang D, Clapper ML,et al.CYP1A1, GSTM1, and GSTT1 polymorphisms, smoking, and lung cancer risk in a pooled analysis among Asian populations.Cancer Epidemiol Biomarkers Prev,2008,17 (5):1120-1126
45 Sobti RC, Kaur P, Kaur S,et al.Combined effect of GSTM1, GSTT1 and GSTP1 polymorphisms on histological subtypes of lung cancer.Biomarkers,2008,13 (3):282-295
46 Sobti RC, Kaur P, Kaur S,et al. Impact of interaction of polymorphic forms of p53 codon 72 and N-acetylation gene (NAT2) on the risk of lung cancer in the North Indian population.DNA Cell Biol,2009,28(9):443-449
47 Lee CN, Yu MC, Bai KJ,et al.NAT2 fast acetylator genotypes are associated with an increased risk for lung cancer with wildtype epidermal growth factor receptors in Taiwan.Lung Cancer,2009,64 (1):9-12
48 McKay JD, Hashibe M, Hung RJ,et al.Sequence variants of NAT1 and NAT2 and other xenometabolic genes and risk of lung and aerodigestive tract cancers in Central Europe.Cancer Epidemiol Biomarkers Prev,2008,17 (1):141-147
49 Kiyohara C, Yoshimasu K, Takayama K, et al. EPHX1 polymorphisms and the risk of lung cancer:a HuGE review. Epidemiology,2006,17 (1):89-99
50 Voho A, Metsola K, Anttila S, et al. EPHX1 gene polymorphisms and individual susceptibility to lung cancer.Cancer Lett,2006,237 (1):102-108
51 Finckh C, Atalla A, Nagel G,et al.Expression and NNK reducing activities of carbonyl reductase and 11beta-hydroxysteroid dehydrogenase type 1 in human lung.Chem Biol Interact,2001,130-132 (1-3):761-773
52 Bear WL, Teel RWEffects of citrus phytochemicals on liver and lung cytochrome P450 activity and on the in vitro metabolism of the tobacco-specific nitrosamine NNK.Anticancer Res,2000,20 (5A):3323-3329
53 Witschi H, Espiritu I, Peake JL, et al. The carcinogenicity of environmental tobacco smoke. Carcinogenesis,1997,18 (3):575-586
54 Jorquera R, Castonguay A, Schuller HM. Effect of tobacco smoke condensate on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by adult and fetal hamster microsomes. Drug Metab Dispos,1993,21 (2):318-324
55 陆宏,李燕.细胞色素P450与肿瘤.生理科学进展,1997,28(2)：178-180
56 von Weymarn LB, Chun JA, Hollenberg PF. Effects of benzyl and phenethyl isothiocyanate on P450s 2A6 and 2A13:potential for chemoprevention in smokers. Carcinogenesis,2006,27 (4):782-790
57 Xin-Yuan Cheng, Guo-Lin Chen, Wei-Xia Zhang, et,al. Arg257Cys polymorphism of CYP2A13 in a Chinese population.Clinica Chimica Acta,2004, 34(3):213-216
58 Zhang X, Chen Y, Liu Y, et al.Single nucleotide polymorphisms of the human cyp2al3 gene:evidence for a null allele.Drug Metab Dispos,2003,31 (9): 1081-1085
59 Cauffiez C, Pottier N, Tournel G, et al. CYP2A13 genetic polymorphism in French Caucasian, Gabonese and Tunisian populations.Xenobiotica,2005,35 (7):661-669
60 Paschke T, Riefler M, Schuler-Metz A, et al.Comparison of cytochrome P450 2A6 polymorphism frequencies in Caucasians and African-Americans using a new one-step PCR-RFLP genotyping method.Toxicology,2001,168 (3): 259-268
61 Smith BD, Sanders JL, Porubsky PR, et al. Structure of the human lung cytochrome P450 2A13. J Biol Chem,2007,282 (23):17306-17313
62王瑾,许峰,周清华.肺癌流行病学研究进展.中国肺癌杂志,2005,8(5)：395-399
63 Spivack SD, Hurteau GJ, Fasco MJ,et al.Phase Ⅰ and Ⅱ carcinogen metabolism gene expression in human lung tissue and tumors.Clin Cancer Res,2003,9(16 Pt1):6002-6011
64 Kiyohara C, Ohno Y.Role of metabolic polymorphisms in lung carcinogenesis.Nippon Koshu Eisei Zasshi,1999,46 (4):241-249
65 Sundberg K, Johansson AS, Stenberg G,et al.Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons. Carcinogenesis, 1998,19 (3):433-6
66 Wiencke JKDNA adduct burden and tobacco carcinogenesis.Oncogene,2002,21 (48):7376-91
67 Ryberg D, Skaug V, Hewer A,et al.Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis,1997,18 (7):1285-1289
68 Ritchie KJ, Henderson CJ, Wang XJ,et al.Glutathione transferase pi plays a critical role in the development of lung carcinogenesis following exposure to tobacco-related carcinogens and urethane.Cancer Res,2007,67 (19):9248-9257
69 Schoket B, Papp G, Levay K,et al.Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure.Mutat Res,2001,482 (1-2):57-69
70 Hu X, Ji X, Srivastava SK,et al.Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene.Arch Biochem Biophys,1997,345 (1):32-38
71 Aldrich MC, Selvin S, Hansen HM,et al.CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification.Cancer Res,2009,69 (6):2340-8
72 Gallagher CJ, Ahn K, Knipe AL,et al. Association between haplotypes of manganese superoxide dismutase (SOD2), smoking, and lung cancer risk.Free Radic Biol Med,2009,46 (1):20-24
73 Yin J, Vogel U, Ma Y,et al.Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population.Mutat Res,2008,641 (1-2):12-18
74黄萌,蔡琳.Haploview与PHASE在单体型研究中的应用.福建医科大学学报,2009,43(4)：310-313
75 Ye Z, Song H, Higgins JP,et al.Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls:meta-analysis of 130 studies.PLoS Med,2006,3 (4):e91
76 Knaapen AM, Schins RP, Polat D,et al.Mechanisms of neutrophil-induced DNA damage in respiratory tract epithelial cells.Mol Cell Biochem,2002,234-235 (1-2):143-51
77 Arlt VM, Schmeiser HH, Osborne MR,et al.Identification of three major DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in rat lung at the C8 and N2 position of guanine and at the N6 position of adenine.Int J Cancer,2006,118 (9):2139-2146
78 Austin GE, Lam L, Zaki SR,et al.Sequence comparison of putative regulatory DNA of the 5'flanking region of the myeloperoxidase gene in normal and leukemic bone marrow cells.Leukemia,1993,7 (9):1445-50
79 London SJ, Lehman TA, Taylor JAMyeloperoxidase genetic polymorphism and lung cancer risk.Cancer Res,1997,57 (22):5001-5013
80吴晓明,周宜开,任恕.髓过氧化物酶基因多态性与肺癌遗传易感性的研究.癌症,2003,22(9)：912-915
81 吕文富,齐军,邢德印.髓过氧化物酶基因G-463A多态与中国人肺癌遗传易感性.中华肿瘤杂志,2002,24(3)：250-253
82张体艳,洪锡田,吴拥军.河南汉族肺癌患者髓过氧化物酶基因多态性分析.郑州大学学报,2007,42(3)：448-449
83 Hoy A, Leininger-Muller B, Kutter D,et al.Growing significance of myeloperoxidase in non-infectious diseases.Clin Chem Lab Med,2002,40 (1): 2-8
84 Dabrowska M, Prokopowicz J, Pietruczuk M,et al.The activity of neutrophil myeloperoxidase in patients with lung carcinoma.Folia Haematol Int Mag Klin Morphol Blutforsch,1988,115 (5):613-9
85 Gresner P, Gromadzinska J, Wasowicz WPolymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer.Lung Cancer,2007,57 (1):1-25
86 Mihi Yang, Yunhee Choi, Bin HwangboCombined effects of genetic polymorphisms in six selected genes on lung cancer susceptibility, lung cancer,2007,5(7):135-142
87 Park JH, Park JM, Kim EJ,et al.Myeloperoxidase-463G>A polymorphism and risk of primary lung cancer in a Korean population.Cancer Detect Prev,2006,30 (3):257-61
88 Loc Le Marchand,Ann Seifried, Annette LumAssociation of the Myeloperoxidase-463G-A Polymorphism with lung cancer risk.Cancer Epidemiology, Biomarkers & Prevention,2000,9:181-184
89 Cascorbi I, Henning S, Brockmoller J,et al.Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant--463A of the myeloperoxidase gene.Cancer Res,2000,60 (3)-:644-649
90 Li-Lian Xu, Geoffrey Liu,David P. Miller, Wei ZhouCounterpoint The MyeloperoxidaseA Polymorphism Does Not.Cancer Epidemiology, Biomarkers & Prevention,2002,11:1555-1559
91 Dally H, Gassner K, Jager B,et al.Myeloperoxidase (MPO) genotype and lung cancer histologic types:the MPO-463 A allele is associated with reduced risk for small cell lung cancer in smokers.Int J Cancer,2002,102 (5):530-535
92 ORHUN H. KANTARCI, TIMOTHY G. LESNICK,PING YANG.. Myeloperoxidase Polymorphism Associated.Mayo Clin Proc,2002,77:17-22
93 Jill Everland Larsen,Maree Louise Colosimo,Ian Anthony YangCYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung.Carcinogenesis,2006,27 (3):525-532
94 Schabath MB, Spitz MR, Hong WK,et al.A myeloperoxidase polymorphism associated with reduced risk of lung cancer.Lung Cancer,2002,37 (1):35-40
95 Nohelia Cajas-Salazar, Carlos H. Sierra-Torres, Salama ACombined effect of MPO GSTM1 and GSTT1 polymorphisms on chromosome aberrations and lung cancer risk.international journal of hygene and enviromental health,2003,20 (6):473-483
96 Liu G, Zhou W, Wang LI,et al.MPO and SOD2 polymorphisms, gender, and the risk of non-small cell lung carcinoma.Cancer Lett,2004,214 (1):69-79
97 Chevrier I, Stucker I, Houllier AM,et al.Myeloperoxidase:new polymorphisms and relation with lung cancer risk.Pharmacogenetics,2003,13 (12):729-39
98 Misra RR, Tangrea JA, Virtamo J,et al.Variation in the promoter region of the myeloperoxidase gene is not directly related to lung cancer risk among male smokers in Finland.Cancer Lett,2001,164 (2):161-167
99 Zienolddiny S, Campa D, Lind H,et al.A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers.Carcinogenesis,2008,29 (6):1164-1169
100 Yoon KA, Kim JH, Gil HJ,et al.CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women.Lung Cancer,2008,60 (1):40-6
101 Van Schooten FJ, Boots AW, Knaapen AM,et al.Myeloperoxidase (MPO)-463G->A reduces MPO activity and DNA adduct levels in bronchoalveolar lavages of smokers.Cancer Epidemiol Biomarkers Prev,2004,13 (5):828-833
102 Kantarci OH, Lesnick TG, Yang P,et al.Myeloperoxidase-463 (G-->A) polymorphism associated with lower risk of lung cancer.Mayo Clin Proc,2002,77 (1):17-22
1 Jemal A, Siegel R, Ward E,et al.Cancer statistics,2009.CA Cancer J Clin,2009, 59 (4):225-249
2 张思维,陈万青,雷正龙等.中国肿瘤登记处2004年恶性肿瘤发病资料分析.中国肿瘤,2008,17(11)：909-912
3 Ferlay J, Autier P, Boniol M,et al.Estimates of the cancer incidence and mortality in Europe in 2006.Ann Oncol,2007,18 (3):581-592
4 Taylor JG, Choi EH, Foster CB,et al.Using genetic variation to study human disease.Trends Mol Med,2001,7 (11):507-512
5 The International HapMap ConsortiumThe International HapMap Project. NATURE,2003,42(6):789-796
6 Gu HF. Single nucleotide polymorphisms(SNPs)and SNP databases. Zhonghua YiXue Yi Chuan Xue Za Zhi,2001,18 (6):479-481
7 Phillips COnline resources for SNP analysis:a review and route map.Mol Biotechnol,2007,35 (1):65-97
8 Dogan I, Onen HI, Yurdakul AS,et al. Polymorphisms in the vitamin D receptor gene and risk of lung cancer.Med Sci Monit,2009,15 (8):BR232-242
9 Rotunno M, Yu K, Lubin JH,et al. Phase I metabolic genes and risk of lung cancer:multiple polymorphisms and mRNA expression. PLoS One,2009,4(5): e5652
10 Landvik NE, Hart K, Skaug V,et al.A specific interleukin-1B haplotype correlates with high levels of IL1B mRNA in the lung and increased risk of non-small cell lung cancer.Carcinogenesis,2009,30 (7):1186-1192
11 Wu W, Zhang W, Qiao R,et al.Association of XPD polymorphisms with severe toxicity in non-small cell lung cancer patients in a Chinese population.Clin Cancer Res,2009,15 (11):3889-3895
12 Yoon KA, Kim JH, Gil HJ,et al.CYPlBl, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women.Lung Cancer,2008,60 (1):40-46
13 Mihi Yang, Yunhee Choi, Bin HwangboCombined effects of genetic polymor-phisms in six selected genes on lung cancer susceptibility.lung cancer,2007,5 (7):135-142
14 Jill Everland Larsen,Maree Louise Colosimo,Ian Anthony YangCYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung. Carcinogenesis,2006,27 (3):525-532
15陈琛,万海粟,周清华.新一代基因测序技术及其在肿瘤研究中的应用.中国肺癌杂志,2010,13(2)：154-160
16 Liu Y, Liu P, Wen W,et al.Haplotype and cell proliferation analyses of candidate lung cancer susceptibility genes on chromosome 15q24-25.1.Cancer Res,2009,69 (19):7844-7850
17 Sun T, Gao Y, Tan W,et al.Haplotypes in matrix metalloproteinase gene cluster on chromosome 11q22 contribute to the risk of lung cancer development and progression.Clin Cancer Res,2006,12 (23):7009-7017
18 Yin J, Vogel U, Ma Y,et al.Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population.Mutat Res,2008,641 (1-2):12-18
19 Amos CI, Wu X, Broderick P,et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.Nat Genet,2008,40 (5):616-622
20 You M, Wang D, Liu P,et al.Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene.Clin Cancer Res,2009,15 (8):2666-2674
21 朱文,周清华.肺癌的遗传易感性和环境致癌.中国肺癌杂志,2003,6(6)：430-433
22谷俊东,滑峰,周清华等.肺癌家族聚集性的系统评价.中国肺癌杂志,2010,13(3)： 224-229
23 Constantin D, Mehrotra K, Rahimtula A,et al. Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes.Environ Health Perspect,1994,102 Suppl 4:161-164
24 Hu X, Ji X, Srivastava SK,et al.Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene.Arch Biochem Biophys,1997,345 (1):32-38
25 Petruska JM, Mosebrook DR, Jakab GJ,et al.Myeloperoxidase-enhanced formation of (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene-DNA adducts in lung tissue in vitro:a role of pulmonary inflammation in the bioactivation of a procarcinogen.Carcinogenesis,1992,13 (7):1075-1081
26 Bear WL, Teel RWEffects of citrus phytochemicals on liver and lung cyto-chrome P450 activity and on the in vitro metabolism of the tobacco-specific nitrosamine NNK.Anticancer Res,2000,20 (5A):3323-3329
27 Hirvonen A, Husgafvel-Pursiainen K, Anttila S,et al.Metabolic cytochrome P450 genotypes and assessment of individual susceptibility to lung cancer. Phar-macogenetics,1992,2 (6):259-263
28陆宏,李燕.细胞色素P450与肿瘤.生理科学进展,1997,28(2)：178-180
29 Shah PP, Singh AP, Singh M,et al.Association of functionally important poly-morphisms in cytochrome P4501B1 with lung cancer. Mutat Res,2008,643 (1-2):4-10
30石云,周宜开,任恕.生物转化酶类基因多态性与肿瘤易感性.国外医学分子生物学分册,2001,235：267-269
31 靳光付,苗瑞芬,路滟等.谷胱甘肽转移酶M1基因多态与胃癌易感性关系的Meta分析.中国肿瘤,2007,16(12)：970-974
32苗瑞芳,邓一枚,陈文森等.细胞色素P450 2E1(CYP2E1)基因多态性与胃癌易感性的Meta分析.中国肿瘤,2007,16(12)：966-969
33 Wang H, Tan W, Hao B,et al.Substantial reduction in risk of lung adeno-carcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK.Cancer Res,2003,63 (22):8057-8061
34 Cauffiez C, Lo-Guidice JM, Quaranta S,et al.Genetic polymorphism of the human cytochrome CYP2A13 in a French population:implication in lung cancer susceptibility.Biochem Biophys Res Commun,2004,317 (2):662-669
35 D'Agostino J, Zhang X, Wu H,et al.Characterization of CYP2A13*2, a variant cytochrome P450 allele previously found to be associated with decreased incidences of lung adenocarcinoma in smokers. Drug Metab Dispos,2008,36 (11):2316-2323
36夏英,张翠兰.CYP450和GST基因多态性与肿瘤易感性研究进展.中华放射医学与防护杂志,2003,235：385-386
37 Lewis SJ, Cherry NM, Niven RM,et al.GSTMl, GSTT1 and GSTP1 poly-morphisms and lung cancer risk.Cancer Lett,2002,180 (2):165-171
38 Cote ML, Chen W, Smith DW,et al.Meta-and pooled analysis of GSTP1 polymorphism and lung cancer:a HuGE-GSEC review.Am J Epidemiol,2009, 169 (7):802-814
39张徐军,闵捷.谷胱甘肽S-转移酶M1、T1基因多态性与儿童急性白血病遗传易感性的Meta分析.环境与健康杂志,2006,23(5)：424-426
40 Habdous M, Siest G, Herbeth B,et al.Glutathione S-transferases genetic polymorphisms and human diseases:overview of epidemiological studies.Ann Biol Clin (Paris),2004,62 (1):15-24
41 Habalova V, Salagovic J, Kalina I,et al.A pilot study testing the genetic poly-morphism of N-acetyltransferase 2 as a risk factor in lung cancer. Neoplasma, 2005,52 (5):364-368
42 Chiou HL, Wu MF, Chien WP,et al.NAT2 fast acetylator genotype is associated with an increased risk of lung cancer among never-smoking women in Taiwan. Cancer Lett,2005,223 (1):93-101
43 Kiyohara C, Yoshimasu K, Takayama K,et al.EPHX1 polymorphisms and the risk of lung cancer:a HuGE review.Epidemiology,2006,17 (1):89-99
44 Chen D, Tian T, Wang H,et al. Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population.Pharmacogenet Genomics,2009,19 (1):25-34
45 Kohno T, Kunitoh H, Suzuki K,et al.Association of KRAS polymorphisms with risk for lung adenocarcinoma accompanied by atypical adenomatous hyper-plasias.Carcinogenesis,2008,29 (5):957-963
46 Chin LJ, Ratner E, Leng S,et al.A SNP in a let-7 microRNA complementary site in the KRAS 3'untranslated region increases non-small cell lung cancer risk. Cancer Res,2008,68 (20):8535-8540
47 Zhang X, Miao X, Guo Y,et al. Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer.Hum Mutat,2006,27 (1):110-117
48 Mechanic LE, Bowman ED, Welsh JA,et al.Common genetic variation in TP53 is associated with lung cancer risk and prognosis in African Americans and somatic mutations in lung tumors.Cancer Epidemiol Biomarkers Prev,2007,16 (2):214-222
49 Choi YY, Kang HK, Choi JE,et al. Comprehensive assessment of P21 poly-morphisms and lung cancer risk.J Hum Genet,2008,53 (1):87-95
50胡志斌,缪小平,马红霞.肺癌易感性与p73基因多态性关系的研究.中华流行病学杂志,2005,262：106-108
51 Sung JS, Han SG, Whang YM,et al.Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer.Lung Cancer, 2008,61 (3):301-308
52 Chen D, Jin G, Wang Y,et al.Genetic variants in peroxisome proliferator-activated receptor-gamma gene are associated with risk of lung cancer in a Chinese population.Carcinogenesis,2008,29 (2):342-350
53 Kim JS, Yim SV, Koh IS,et al.Single-nucleotide polymorphisms (SNPs) and haplotype analysis in vascular endothelial growth factor (VEGF) gene in the patients with Parkinson disease and lung cancer.Arch Gerontol Geriatr,2009,48 (3):287-290
54 Zhai R, Liu G, Zhou W,et al.Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non-small cell lung cancer.Clin Cancer Res, 2008,14 (2):612-617
55 Jo UH, Han SG, Seo JH,et al.The genetic polymorphisms of HER-2 and the risk of lung cancer in a Korean population.BMC Cancer,2008,8:359
56 Su L, Zhou W, Asomaning K,et al.Genotypes and haplotypes of matrix metalloproteinase 1,3 and 12 genes and the risk of lung cancer. Carcinogenesis, 2006,27 (5):1024-1029
57 Sauter W, Rosenberger A, Beckmann L,et al.Matrix metalloproteinase 1 (MMP1) is associated with early-onset lung cancer.Cancer Epidemiol Biomarkers Prev,2008,17 (5):1127-1135
58 Lee WK, Kim JS, Kang HG,et al.Polymorphisms in the Caspase7 gene and the risk of lung cancer.Lung Cancer,2009,65 (1):19-24
59 Jang JS, Kim KM, Choi JE,et al.Identification of polymorphisms in the Caspase-3 gene and their association with lung cancer risk.Mol Carcinog,2008,47 (5): 383-390
60 Son JW, Kang HK, Chae MH,et al.Polymorphisms in the caspase-8 gene and the risk of lung cancer. Cancer Genet Cytogenet,2006,169 (2):121-127
61 Park JY, Park JM, Jang JS,et al.Caspase 9 promoter polymorphisms and risk of primary lung cancer. Hum Mol Genet,2006,15 (12):1963-1971
62 Shin S, Sung B J, Cho YS,et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7.Biochemistry,2001,40 (4):1117-1123
63 Suzuki A, Ito T, Kawano H,et al.Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene,2000,19 (10):1346-1353
64 Jang JS, Kim KM, Kang KH,et al.Polymorphisms in the survivin gene and the risk of lung cancer.Lung Cancer,2008,60 (1):31-39
65 Hu Z, Wang H, Shao M,et al.Genetic variants in MGMT and risk of lung cancer in Southeastern Chinese:a haplotype-based analysis.Hum Mutat,2007,28 (5): 431-440
66 Yin J, Vogel U, Ma Y,et al.HapMap-based study of the DNA repair gene ERCC2 and lung cancer susceptibility in a Chinese population. Carcinogenesis, 2009,30 (7):1181-1185
67 Cote ML, Yoo W, Wenzlaff AS,et al.Tobacco and estrogen metabolic poly-morphisms and risk of non-small cell lung cancer in women. Carcinogenesis, 2009,30 (4):626-635
68 Ma H, Xu L, Yuan J,et al.Tagging single nucleotide polymorphisms in excision repair cross-complementing group 1 (ERCC1) and risk of primary lung cancer in a Chinese population. Pharmacogenet Genomics,2007,17 (6):417-423
69 Yin J, Vogel U, Ma Y,et al. A haplotype encompassing the variant allele of DNA repair gene polymorphism ERCC2/XPD Lys751Gln but not the variant allele of Asp312Asn is associated with risk of lung cancer in a northeastern Chinese population.Cancer Genet Cytogenet,2007,175 (1):47-51
70 Kiyohara C, Yoshimasu KGenetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk:a meta-analysis.Int J Med Sci,2007,4 (2): 59-71
71 Tseng RC, Hsieh FJ, Shih CM,et al.Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes:a multiple genotype-phenotype study. Cancer,2009,115(13):2939-2948
72 Ma H, Hu Z, Wang H,et al.ERCC6/CSB gene polymorphisms and lung cancer risk.Cancer Lett,2009,273 (1):172-176
73 Chang CH, Hsiao CF, Chang GC,et al.Interactive effect of cigarette smoking with human 8-oxoguanine DNA N-glycosylase 1 (hOGGl) polymorphisms on the risk of lung cancer:a case-control study in Taiwan. Am J Epidemiol,2009, 170 (6):695-702
74 Okasaka T, Matsuo K, Suzuki T,et al.hOGG1 Ser326Cys polymorphism and risk oflung cancer by histological type. J Hum Genet,2009,54 (12):739-745
75 Li H, Hao X, Zhang W,et al. The hOGG1 Ser326Cys polymorphism and lung cancer risk:a meta-analysis. Cancer Epidemiol Biomarkers Prev,2008,17 (7): 1739-1745
76 Lee YC, Morgenstern H, Greenland S,et al.A case-control study of the association of the polymorphisms and haplotypes of DNA ligase I with lung and upper-aerodigestive-tract cancers. Int J Cancer,2008,122 (7):1630-1638
77 Danoy P, Michiels S, Dessen P,et al.Variants in DNA double-strand break repair and DNA damage-response genes and susceptibility to lung and head and neck cancers.Int J Cancer,2008,123 (2):457-463
78 Engels EA, Wu X, Gu J,et al. Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer.Cancer Res,2007,67 (13): 6520-6527
79 Gervasini G, Carrillo JA, Garcia M,et al.Adenosine triphosphate-binding cassette Bl (ABCB1) (multidrug resistance 1) G2677T/A gene polymorphism is associated with high risk of lung cancer. Cancer,2006,107 (12):2850-2857
80 Gu J, Gong Y, Huang M,et al.Polymorphisms of STK15 (Aurora-A) gene and lung cancer risk in Caucasians.Carcinogenesis,2007,28 (2):350-355
81 Kim JH, Kim H, Lee KY,et al.Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. Hum Mol Genet,2006,15 (7):1181-1186
82 Wang H, Hao B, Chen X,et al.Beta-2 adrenergic receptor gene (ADRB2) polymorphism and risk for lung adenocarcinoma:a case-control study in a Chinese population.Cancer Lett,2006,240 (2):297-305
83 Kang HG, Chae MH, Park JM,et al.Polymorphisms in TGF-betal gene and the risk of lung cancer.Lung Cancer,2006,52 (1):1-7
84 Lee SJ, Jeon HS, Jang JS,et al.DNMT3B polymorphisms and risk of primary lung cancer.Carcinogenesis,2005,26 (2):403-409
85 俞晓静,陈坤,金明娟.5,10-亚甲基四氢叶酸还原酶基因多态性与结直肠癌易感性关系的Meta分析.中国慢性病预防与控制,2006,14(2)：115-118
86 Liu CS, Tsai CW, Hsia TC,et al.Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients.Cancer Genomics Proteomics,2009,6 (6):325-329
87 Boccia S, Boffetta P, Brennan P,et al.Meta-analyses of the methylenetetra-hydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer.Cancer Lett,2009,273 (1):55-61
88 陈文森,靳光付,邓一枚.IGF1和IGFBP3多态性与乳腺癌易感性的Meta分析.中国肿瘤,2007,16(12)：975-978
89 Nacak M, Nacak I, Sanli M,et al.Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey.Cancer Genet Cytogenet,2010,198 (1):22-26
90 Mita Y, Yasuda Y, Sakai A,et al.Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers. J Cancer Res Clin Oncol,2010,136 (2):249-259
91 Agachan B, Kucukhuseyin O, Aksoy P,et al.Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking. Anticancer Res,2009,29 (6):2417-2420
92 Lo YL, Jou YS, Hsiao CF,et al.A polymorphism in the APE1 gene promoter is associated with lung cancer risk.Cancer Epidemiol Biomarkers Prev,2009,18 (1):223-229
93 Arslan S, Silig Y, Pinarbasi HAn investigation of the relationship between SULT1A1 Arg(213)His polymorphism and lung cancer susceptibility in a Turkish population.Cell Biochem Funct,2009,27 (4):211-215
94 Miao R, Gu H, Liu H,et al.Tagging single nucleotide polymorphisms in MBD4 are associated with risk of lung cancer in a Chinese population.Lung Cancer, 2008,62 (3):281-286
95 Bernig T, Chanock SJChallenges of SNP genotyping and genetic variation:its future role in diagnosis and treatment of cancer.Expert Rev Mol Diagn,2006,6 (3):319-331
96 Wang Y, Armstrong SAGenome-wide SNP analysis in cancer:leukemia shows the way.Cancer Cell,2007,11 (4):308-309
97 Craig DW, Stephan DAApplications of whole-genome high-density SNP genotyping. Expert Rev Mol Diagn,2005,5 (2):159-170
98 Wang Y, Broderick P, Matakidou A,et al.Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers.Carcinogenesis,2010,31 (2):234-238
99 Zienolddiny S, Skaug V, Landvik NE,et al.The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung. Carcinogenesis,2009,30 (8):1368-1371
100 Falvella FS, Galvan A, Frullanti E,et al.Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk.Clin Cancer Res,2009,15 (5):1837-1842
101 Inoue I. SNP database and establishment of personalized medicine..Nippon Yakurigaku Zasshi,2002,120 (1):41-42
102 Iida A, Saito S, Sekine A,et al. SNP collection, pharmacogenomics, and the future of drug therapy.Gan To Kagaku Ryoho,2002,29 (9):1665-1673
103 Sohn JW, Lee SY, Lee SJ,et al. MDR1 polymorphisms predict the response to etoposide-cisplatin combination chemotherapy in small cell lung cancer.Jpn J Clin Oncol,2006,36 (3):137-141
104 Han JY, Lim HS, Shin ES,et al.Influence of the organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphisms on irinotecan-pharmacokinetics and clinical outcome of patients with advanced non-small cell lung cancer.Lung Cancer,2008,59 (1):69-75
105 Liu G, Gurubhagavatula S, Zhou W,et al.Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib.Pharmacogenomics J,2008,8 (2):129-138
106 Heist RS, Zhou W, Wang Z,et al.Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer.J Clin Oncol,2008,26 (34):5596-5602
107 Kim HT, Lee JE, Shin ES,et al.Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy. J Clin Oncol,2008,26 (36):5972-5979
108 Pine SR, Mechanic LE, Ambs S,et al.Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene.J Natl Cancer Inst,2007,99 (18):1401-1409
109 Yoon SM, Hong YC, Park HJ,et al.The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy.Int J Radiat Oncol Biol Phys,2005,63 (3):885-891