CYP1A1 Ile462Val多态与小细胞肺癌遗传易感性相关

目的探讨细胞色素P450 1A1(CYP1A1)基因Ile462Val单核苷酸多态与小细胞肺癌遗传易感性的相关关系。方法收集275例小细胞肺癌患者和406例正常对照者的外周静脉血标本,采用聚合酶链反应-限制性片断长度多态性分析(PCRRFLP)技术检测CYP1A1基因Ile462Val多态的基因型。采用多变量Logistic回归方法分析不同基因型与小细胞肺癌发病风险的相关关系。结果与CYP1A1 462 Ile/Ile基因型携带者相比,462 Ile/Val和462 Val/Val基因型携带者小细胞肺癌发病风险显著降低,其OR值分别为0.65(95%CI 0.48~0.91)和0.60(95%CI 0.32~0.97)。吸烟分层分析显示,在不吸烟人群中,462 Ile/Val或462 Val/Val基因型携带者小细胞肺癌发病风险的OR值为0.99(95%CI 0.62~1.51)。在吸烟人群中,462Ile/Val或462 Val/Val基因型携带者小细胞肺癌发病风险的OR值为0.42(95%CI0.26~0.65)。此外,在轻度吸烟者和重度吸烟者中462 Ile/Val或462 Val/Val基因型携带者小细胞肺癌发病风险的OR值分别为0.42(95%CI 0.21~0.85)和0.44(95%CI 0.24~0.82)。结论 CYP1A1基因Ile462Val多态与小细胞肺癌遗传易感性相关。     

细胞色素P4501A1基因多态性在胃癌发生中的交互作用

目的：探讨CYP1A1突变基因型与吸烟、饮酒因素对胃癌发生的交互作用及作用方式。方法：以社区为基础的病例对照研究,病例为胃镜及病理确诊的肠型胃癌,共112例,以同期上消化道肿瘤病例的“健康”同胞、配偶和配偶的同胞为对照组,共676例,用多聚酶链反应和限制性片段长度多态性法检测其基因型,多基因logistic回归模型分析与胃癌的相关性。结果：在调整混杂因素的影响后,未见CYP1A1突变基因型与胃癌危险性之间有统计学关联;但CYP1A1基因型与吸烟对胃癌发生有明显交互作用,显增加胃癌的危险性,交互作用系数γ为2．82,OReg值为5．00,为2型交互作用中的超相乘模型,进一步分析剂量反应关系显示;突变基因型与吸烟量,开始吸烟年龄均呈“低暴露－基因效应”方式。即随着暴露剂量的增加,交互作用的强度逐渐降低。CYP1A1突变基因型与饮酒史的交互作用有减弱效应,OReg值为2．22,γ为0．46,但呈“高暴露－基因效应”。结论CYP1A1突变基因型与吸烟、饮酒对胃癌均有交互作用,但交互作用的方式不同。这些结果提示CYP1A1突变基因型的个体应完成戒烟、限制大量饮酒、以预防胃癌的发生。     

二氧化硫对大鼠细胞色素P4501A的抑制作用

目的探讨二氧化硫（sch）对肝、肺微粒体细胞色素P4501A1及1A2的影响。方法采用动式染毒技术给予雄性Wistar大鼠不同浓度SO2，染毒。采用荧光分光光度法和荧光实时定量RT—PCR方法测定各组大鼠肝、肺微粒体CYP1A1和CYP1A2活性及mRNA表达水平。结果随着SO2吸入浓度增加，大鼠肝肺CYP1A1和1A2mRNA表达水平，肝微粒体CYP1A1活性、肺微粒体CYP1A1和1A2活性逐渐降低，且存在明显的剂量一效应关系；肝微粒体CYP1A2活性在56mg／mosch处理组降低显著。结论SO2可降低大鼠肝、肺微粒体CYP1A1和1A2活性和mRNA水平，吸入SO2后肝、肺对外源化合物及药物的代谢可能会受到影响。     

SAM肝细胞色素P450 3A对衰老的作用

为探讨衰老与细胞色素Ｐ４５０３Ａ（ＣＹＰ３Ａ）活性的关系,用红霉素Ｎ－脱甲酶活性测定法分别检测了ＳＡＭ－Ｒ１、ＳＡＭ－Ｐ１和ＳＡＭ－Ｐ８三组衰老加速鼠（ＳＡＭ）中肝微粒体细胞色素Ｐ４５０３Ａ的活性,每组动物分为７、１３、３６周龄组。结果发现ＳＡＭ随年龄增长ＣＹＰ３Ａ的活性均降低,１３周龄组尤为显著,ＳＡＭ－Ｒ１组ＣＹＰ３Ａ活性下降约７２％（ｔ＝２６１,Ｐ＜００２）;ＳＡＭ－Ｐ１组ＣＹＰ３Ａ活性下降约７３％（ｔ＝２．７４,Ｐ＜００２）;ＳＡＭ－Ｐ８组中ＣＹＰ３Ａ活性降低约８６％（ｔ＝３．１４,ｐ＜０．００５）。ＳＡＭ－Ｐ１组ＣＹＰ３Ａ活性３６周龄比３周龄组下降约３５％,呈缓慢进行;ＳＡＭ－Ｒ１和ＳＡＭ－Ｐ８组中１３至３６周龄组均无明显变化。提示细胞色素Ｐ４５０３Ａ对衰老有重要影响作用。     

硫酸镉对PL／P450 1A1细胞中人肺癌易感基因P450 1A1？…

目的 观察重金属化合物硫酸镉（ＣｄＳＯ４）在体外对人羊膜ＦＬ／Ｐ４５０ １Ａ１细胞内Ｐ４５０ １Ａ１ＤＮＡ序列的改变和，了解镉化合物对肺癌易感基因的影响。方法 利用不同剂量的ＣｄＳＯ４处理ＦＬ／Ｐ４５０ １Ａ１细胞，其半数抑制浓度（ＩＣ５０）为２４．５５ｍｇ／ｍｌ。以１／４ ＩＣ５０终浓度ＣｄＳＯ４处理ＦＬ／Ｐ４５０ １Ａ１细胞４８ｈ后提取细胞ｐＲＥＰ ９／Ｐ４５０ １Ａ１质粒。由于ｐＲＥＰ９缺少     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

目的 利用以核心家系为基础的关联研究探讨细胞色素P450酶系(cytochrome P450,CYP450)CYP1A1基因m1和m2多态性并分析其与鼻咽癌易感性的关联.方法 收集457个广东鼻咽癌核心家系(每个核心家系由患者和父母或同胞构成)共2134名成员作为研究对象,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对CYPlAl基因单核苷酸多态性(SNP)位点m1和m2(其参考编号分别为rs4646903和rs1048943)进行基因分型.挑选PCR产物测序验证.运用家系为基础的相关性检验(family-based association test,FBAT)软件分析这两个多态位点的基因型及其单体型与鼻咽癌易感性的关联.结果 FBAT软件分析结果 显示,位点m1和m2的微效等位基因频率(MAF)分别为0.442(C)和0.339(G).其中无论是否根据EB病毒壳抗原抗体(VCA-IgA)分层,m1位点与鼻咽癌的易感性之间关联均无统计学意义[未分层:X2=2.399,P=0.301;分层后:低滴度组(VCA-IgA<1:80),MAF=0.457(C),X2=1.221,P=0.543;高滴度组(VCA-IgA≥1:80),MAF=0.427(C),X2=2.832,P=0.243];对m2位点来说,末根据VCA-IgA分层时,该位点与鼻咽癌的易感性之间关联无统计学意义(X2=2.694,P=0.260).分层后,在低滴度组,累加和显性模式下,位点m2等位基因G显示了从亲代到子代传递减少[MAF=0.347(G);Z<,累加>=-2.120,P<,累加>=0.034;Z显性=-2.303,P显性=0.021],全局统计也提示了传递的改变(X2=5.394,P=0.067);由这两个位点构建的单体型TG(0.057)可能降低鼻咽癌的发病风险(Z=-2.002,P=0.045),全局统计也提示CYP1A1基因单体型可能与鼻咽癌易感性有关系(X2=7.067,P=0.070).结论 以家系为基础的相关性研究发现CYP1A1基因多态位点m1与鼻咽癌的易感性之间关联无统计学意义,位点m2基因多态性可能与鼻咽癌的发病风险降低有关系.     

细胞色素P450 1A1-Wt和Asn461、Vla462真核表达载体的构建及人胚肺成纤维细胞转染

目的构建能够高效表达细胞色素P450 1A1（CYP 1A1）蛋白的细胞株，分析不同基因型蛋白表达的差异。方法首先将已经建立的T载体中CYP1A1-Wt和Asn^461、Val^462的CYP1A1片断重组至pBABE-neo载体上，转染入人胚肺成纤维细胞（HLF），G418筛选获得阳性细胞，Western-Blot检测CYP1A1蛋白的表达，观察细胞形态，生长曲线，恶变性等生物学特性的改变。结果CYP1A1野生型、变异型转染的HLF细胞均能高效表达CYP1A1蛋白，其生物学特性与正常细胞无显著差异，也不属于恶性细胞。结论通过细胞转染和筛选获得了表达CYP1A1蛋白的细胞株。     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

硫酸镉对FL/P450 1A1细胞中人肺癌易感基因P450 1A1的影响

目的　观察重金属化合物硫酸镉 (CdSO4 )在体外对人羊膜FL/P45 0 1A1细胞内P45 01A1DNA序列的改变作用 ,了解镉化合物对肺癌易感基因的影响。方法　利用不同剂量的CdSO4 处理FL/P45 0 1A1细胞 ,其半数抑制浓度 (IC50 )为 2 4.5 5mg/ml。以 1/ 4IC50 终浓度CdSO4 处理FL/P45 0 1A1细胞 48h后提取细胞pREP 9/P45 0 1A1质粒。由于 pREP 9缺少通用序列 ,BamHI酶切 ,低熔点琼脂糖电泳分离P45 0 1A1cDNA片段。BamHI酶切 pGEM～ 3Zf( ) ,CIP处理 ,并与 2倍摩尔P45 0 1A1cDNA片段混合 ,乙醇沉淀 ,沉淀物加入 18μlTE ,加 2 μl 10倍连接酶缓冲液 ,混匀 ,加10UT4DNA连接酶 ,混匀 ,12℃保温 16～ 2 0h。凝胶电泳分析连接结果。鉴定合格连接物转化DH5α菌 ,X gal喷洒对重组子进行蓝 /白颜色筛选。选择含重组子的宿主菌进行P45 0 1A1cDNA测序。结果　在体外 ,CdSO4 未引起FL/P45 0 1A1cDNA序列改变。结论　CdSO4 对FL/P45 0 1A1细胞中肺癌易感基因P45 0 1A1cDNA没有影响     

CYP1A1及GSTP1基因多态性与肺癌易感性关系

目的 探讨细胞色素P4501A1(CYP1A1)Exon7和谷胱甘肽硫转移酶P1(GSTP1)Ile¹⁰⁵Val基因多态性与内蒙古地区汉族人群肺癌易感性关系。方法 采用等位基因特异性扩增法分析216例汉族对照人群和116例肺癌患者CYP1A1 Exon7和GSTP1 Ile¹⁰⁵Val基因多态性。结果 携带CYP1A1 Exon7突变杂合型和纯合型的个体患肺癌的危险均升高(OR值分别为1.460和1.593),而携带GSTP1 Ile¹⁰⁵Val突变杂合型和纯合型的个体患肺癌的风险均降低(OR值分别为0.970和0.602);CYP1A1 Exon7和GSTP1 Ile¹⁰⁵Val基因在肺癌易感性方面无协同作用;CYP1A1 Exon7与吸烟有协同作用(OR=2.637,95%CI=1.056~6.530,P=0.032),GSTP1 Ile¹⁰⁵Val与吸烟无协同作用。结论 CYP1A1 Exon7突变基因型为肺癌的可疑易感因素,CYP1A1 Exon7突变基因型和吸烟对肺癌易感有协同作用,GSTP1 Ile¹⁰⁵Val突变基因型可降低肺癌易感性。     

苯并[a]芘诱导内皮细胞细胞色素P4501A1表达的研究

目的：探讨苯并[a]芘(BaP)诱导猪主动脉内皮细胞细胞色素P4501A1(CYP1A1)表达及活性的影响。方法：离体培养猪主动脉内皮细胞，不同浓度BaP(0、0．5、1．0、5．0、10．0μmol／L)染毒24h，分别以Western-blot法和免疫组化方法检测不同浓度BaP诱导内皮细胞合成CYP1A1的影响，同时还探讨了乙氧基异吩噁唑-o-去乙氧基酶(EROD)活力的变化规律。结果：Western-blot法未能检测出对照组CYP1A1的表达，而各染毒组均检出了CYP1A1的表达；免疫组化结果显示染毒组仅在部分内皮细胞呈阳性反应；EROD活力诱导高峰的BaP浓度为0．5～1.0μmol／L。结论：BaP可诱导部分猪主动脉内皮细胞合成CYP1A1；EROD活力诱导高峰的BaP浓度为0．5～1．0μmol／L。     

GSTT1及CYP1A1基因多态性与肺癌易感性关系

目的 探讨细胞色素P4501A1(CYP1A1)和谷胱甘肽硫转移酶T1(GSTT1)基因多态性与肺癌易感性的关系.方法 用等位特异性PCR(AS-PCR)及多重PCR技术分析106例肺癌患者和250名健康人的CYP1A1、GSTT1基因多态性、基因型分布频率和交互作用.结果 携带CYP1A1(Val/Val)/GSTT1(-)基因型的人患肺癌的风险明显增加(P=0.025);吸烟与肺癌易感性有关(P=0.037),吸烟者患肺癌的风险明显增加(OR=1.628.95%CI=1.028～2.577);携带CYP1A1(Val/Val)基因的吸烟者较携带CYP1A1(Ile/Ile)基因型的不吸烟者易患肺癌(P=0.033);携带GSTT1(-)的吸烟者患肺癌的风险明显增加(P=0.045).结论 CYP1A1突变型和GSTT1(-)基因型是肺癌的可疑易患因素,二者对肺癌的发生有协同作用,但单独携带CYP1A1突变型或GSTT1(-)基因型肺癌易感性差异无统计学意义,吸烟与肺癌易感性有关;CYP1A1突变型、GSTT1(-)基因型与吸烟在肺癌的发生上有相互促进作用.     

CYP1A1基因多态性及血清锌水平与非小细胞肺癌的关系

[目的]探讨细胞色素P450(A)(CYP1A1)的基因多态性、血清锌水平单独作用以及联合作用与非小细胞肺癌发生危险的关系.[方法]采用病例对照研究方法,病例78例,对照78例.用限制性片断长度多态性PCR技术(PCR-RFLP)检测CYP1A1的MspI多态性,用电感耦合等离定子体发射光谱法(ICP-AES)测血清锌水平.[结果]CYP1A1的MspI多态性单独作用时与肺癌危险性关系差异无统计学意义(P>0.05);病例组血清锌水平显著低于对照组(P<0.01);以血清锌≥117.0mg/dL且CYP1A1野生型基因携带者为参照组(OR=1.00),则血清锌<117.0mg/dL且携带CYP1A1突变型或杂合型或野生型基因者的OR分别为5.50(P<0.05)、10.63(P<0.01)、10.08(P<0.01).[结论]CYP1A1基因多态性单独作用时NSCLC发生无显著相关;血清锌水平与NSCLC发生呈负相关;CYP1A1基因多态性与血清锌联合作用时明显提高NSCLC发生的危险性,在NSCLC发生中存在协同作用.     

中国居民细胞色素P450 2E1基因多态性与食管癌易感性关系的Meta分析

[目的]探讨中国居民CYP2E1基因多态性与食管癌易感性的关系。[方法]检索中国生物医学文献数据库（CBM）和PubMed,并收集相关文献进行Meta分析。以病例组和对照组CYP2E1基因型分布的比值比（OR）为效应指标,对文献进行评价筛选、异质性检验,应用Meta分析软件RevMan5对各研究原始数据进行统计。[结果]最终纳入系统评价进行Meta分析的共有8个病例对照研究,其中食管癌患者879例,对照1155例。Meta分析结果合并OR=2．07,95％CI=1．18～3．64。[结论]对目前相关研究结果的Meta分析显示中国居民CYP2E1基因多态性与食管癌易感性之间有关联,CYP2E1基因纯合子野生型C1／C1是食管癌的易感性基因。     

Evidence-based prevention (EBP): A review of cytochrome P450 expression in the bronchial epithelium and new approach to lung cancer prevention

The number of fatalities in Japan attributable to lung cancer exceeded 50000 in 2001. It is socially desirable that various markers, which can be utilized for the prevention of lung cancer, be established. We believe that smoking or exposure to carcinogens in air induces mutations in bronchial and alveolar epithelia, leading to the development of lung cancer. It would be useful to have markers of individual differences in susceptibility to chemical carcinogen-induced lung cancer 1) to identify genetic polymorphisms of enzymes metabolizing chemical carcinogens and 2) to investigate the expression of enzymes metabolizing chemical carcinogens. In this paper, we review CYP expression in the bronchial epithelium. CYP1, CYP2 and CYP3 are expressed in the bronchial epithelium. We also show the relationship between the genetic polymorphisms of cytochrome P450 (CYP) and a person’s susceptibility to chemical carcinogen-induced lung cancer. We demonstrate the relationship between cigarette consumption and the CYP expression profile in the bronchial epithelium. To maintain and promote public health, we must apply evidence, such as CYP polymorphisms and CYP profiles to disease prevention and also to aggressively advance evidence-based prevention (EBP) of lung cancer. This article is based upon the research that was given Encouragement Award at the 75th Annual Meeting of the Japanese Society for Hygiene held in Niigata, Japan on March 27–30, 2005.     

脂氧酶12 -183G＞A变异影响非小细胞肺癌发病风险

摘要:目的　探讨位于脂氧酶12（LOX12）基因启动子区-183G＞A单核苷酸多态与非小细胞肺癌发病风险之间的关系。方法　选取非小细胞肺癌患者956例及健康对照994例,利用PCR-限制性片段长度多态性方法进行基因分型,以多变量Logistic回归分析比值比（OR）及其95%可信区间（95%CI）。结果　LOX12 -183GG、GA、AA各基因型频率在病例组分别是20.8%、53.6%、25.6%,在正常对照组分别为26.8%、52.2%、21.0%。与-183GG基因型相比,AA基因型明显增加非小细胞肺癌的发病风险,其OR（95%CI）为1.53（1.17～2.00）;而GA基因型并不增加非小细胞肺癌发病风险,其OR（95%CI）值为1.23（0.98～1.55）。吸烟分层分析显示,以携带-183GG基因型的不吸烟者为参照,携带-183AA基因型的重度吸烟者发生非小细胞肺癌的风险为9.12（95% CI:5.07～16.41,P＜0.001）,大于不吸烟但携带-183AA 基因型者的OR值（OR＝2.03,95% CI:1.34～3.09,P＝0.001）与重度吸烟但携带-183GG基因型OR值（OR＝6.84,95%CI:3.81～12.31,P＜0.001）之和。结论　LOX12 基因启动子区-183G＞A单核苷酸多态可与吸烟交互作用共同增加非小细胞肺癌发病风险。