细胞色素P4501A1,2D6和谷胱甘肽硫转移酶基因多态性与肺癌易感性的研究

目的探讨细胞色素Ｐ４５０１Ａ１（ＣＹＰ１Ａ１），２Ｄ６（ＣＹＰ２Ｄ６）和谷胱甘肽硫转移酶（ＧＳＴＭ１）基因多态性与肺癌易感性的关系。方法用病例对照研究方法及ＰＣＲ┐ＲＦＬＰ等技术检测原发性肺癌和住院对照各５９例，分析ＣＹＰ１Ａ１基因ＭｓｐＩＣ型、ＣＹＰ２Ｄ６Ｃｈ型（Ｔ／Ｔ型）和ＧＳＴＭ１缺陷型〔ＧＳＴＭ１（－）〕三种纯合突变型频率分布及其交互作用。结果突变型在病例和对照组的频率分别为（ＣＹＰ１Ａ１ＭｓｐＩＣ型２５．４％、１５．３％（Ｐ＝０．１７），ＣＹＰ２Ｄ６ＣｈＴ／Ｔ型３５．６％，４７．５％（Ｐ＝０．２６），ＧＳＴＭ１（－）型５７．６％、４９．２％（Ｐ＝０．４６），无显著性差异。协同分析发现在男性中，１１．６％（５／４３）肺癌兼有ＭｓｐＩＣ型和ＧＳＴＭ１（－）型，对照组无１例（０／４３），Ｐ＝０．０３。结论结果提示在男性中ＣＹＰ１Ａ１ＭｓｐＩＣ型和ＧＳＴＭ１（－）型可能协同增加患肺癌的危险性。     

代谢酶基因多态性与胃癌的相关性分析

目的　探讨代谢酶细胞色素Ｐ４５０ ２Ｅ１（ＣＹＰ２Ｅ１）和谷胱甘肽转硫酶Ｍ１（ＧＳＴＭ１） 基因多态性与胃癌的关系。方法　应用聚合酶链反应和限制性片段长度多态性技术对胃癌高发区福建省长乐市原发性胃癌病例９１ 例和正常对照９４ 例进行ＣＹＰ２Ｅ１ 与ＧＳＴＭ１ 基因型检测和分析。结果　胃癌病例与对照的ＣＹＰ２Ｅ１ 等位基因Ｃ１ 和Ｃ２ 频率差异有显著性（χ２ ＝４．９１，Ｐ＜０ ．０５） 。ＧＳＴＭ１ 基因缺失率在胃癌组和对照组分别是６１．５％ 和４５．７％ ，ＧＳＴＭ１基因缺失与胃癌易感性有关（ＯＲ＝１．９０，９５％ 可信限＝ １．０１～３．５６） 。携带ＣＹＰ２Ｅ１ 的Ｃ２／Ｃ２ 基因和ＧＳＴＭ１ 缺失基因型者长期摄入鱼露可增加胃癌发生的危险。结论　代谢ＣＹＰ２Ｅ１ 和ＧＳＴＭ１ 基因多态可能与胃癌的发生有关。     

应用等位基因特异性PCR和多重差别PCR检测肺癌患者CYP1A1和GSTM1的遗传多态性

本文对等位基因特异性ＰＣＲ（Ａｌｅｌｅｓｐｅｃｉｆｉｃ,ＡＳ）和多重差别（Ｍｕｌｔｉｐｌｅｘｄｉｆｅｒｅｎｔｉａｌ,ＭＤ）ＰＣＲ技术进行了优化,并用此法联合检测了１０５例江苏地区健康人群及６８例肺癌患者ＣＹＰ１Ａ１、ＧＳＴＭ１的等位基因型。结果表明：ＡＳＰＣＲ及ＭＤＰＣＲ采用的设立双参照扩增体系,可一次同时检测ＣＹＰ１Ａ１和ＧＳＴＭ１的等位基因型。在肺癌患者组中,ＣＹＰ１Ａ１的突变型Ｖａｌ／Ｖａｌ的频率１２／６８（１７．６％）约为健康组９／１０５（８．５７％）的２０５倍,而ＧＳＴＭ１纯合缺失的频率,肺癌组为３９／６８（５７３％）,与健康对照组４２／１０５（４０％）相比,亦有显著增加（Ｐ＜０．０５）。     

应用等位基因特异性PCR和多重差别检测肺癌患者CYP1A1和GSTM1 …

本文对等位基因特异性ＰＣＲ和多重差别ＰＣＲ技术进行了优化,并用此法联合检测了１０５例江苏地区健康人群及６８例肺癌患者ＣＹＰ１Ａ１、ＧＳＴＭ１的等位基因型。结果表明,ＡＳ－ＰＣＲ及ＭＤ－ＰＣＲ采用的设立双参照扩增体系,可一次同时检测ＣＹＰ１Ａ１和ＧＳＴＭ１的等位基因型。在肺癌患者组中,ＣＹＰ１Ａ１的突变型Ｖａｌ／Ｖａｌ的频率１２／６８约为健康组９／１０５（８．５７％）的２．０５倍,而ＧＳＴＭ１纯合缺     

ＧＳＴＭ１基因多态性与川北地区肺癌易感性关系的研究

目的　探讨谷胱苷肽硫转移酶Ｍ１（ＧＳＴＭ１）基因多态性与川北地区汉族人群肺癌易感性的关系。方法　采用病例对照研究和聚合酶链式反应（ＰＣＲ）技术检测川北地区１２５例肺癌患者（肺癌组）和１２５例非肿瘤患者（对照组）ＧＳＴＭ１基因缺失型的频率,评价其与肺癌易感性的关系。结果　ＧＳＴＭ１缺失基因型［ＧＳＴＭ１（－）］频率在肺癌组和对照组分别为５８.４％和５６.８％,差异无统计学意义（Ｐ＝０.８２２）;ＧＳＴＭ１（－）基因型与肺鳞癌（ＯＲ＝０.９７,９５％ＣＩ：０.５２～１.８３,Ｐ＝０.９３４）和腺癌（ＯＲ＝０.９４,９５％ＣＩ：０.４２～２.０４,Ｐ＝０.８４４）风险亦无明确关系。结论　ＧＳＴＭ１各基因型与肺癌风险无明确关系。     

华人GSTM1,CYP1A1与2E1和APOE等等位基因的基因型

目的探讨华人ＧＳＴＭ１、ＣＹＰ１Ａ１与２Ｅ１，和ＡｐｏＥ等等位基因的基因型，将有助于研究肿瘤病因，环境有害物和机体的相互作用，以及药物代谢。方法收集９５例上海和８９例哈尔滨正常女性的血液，提取ＤＮＡ，作ＣＹＰ１Ａ１、２Ｅ１，ＧＳＴＭ１和ＡｐｏＥ等基因型的分析。结果ＧＳＴＭ１缺失占５２％。ＣＹＰ１Ａ１第７外显子Ａ┐Ｇ突变型纯合子（ｍｍ）占３．９％，突变型等位基因占２２．３％。ＣＹＰ２Ｅ１５′端调控区Ｃ┐Ｔｍｍ占１．６％，突变型等位基因占２３．６％；第六内含子Ｔ┐Ａｍｍ占５．１％，突变型等位基因占２６．４％。ＡｐｏＥ的ε２占８．４％，ε４占９．０％。２５０例ＣＹＰ２Ｄ６中仅１例为２Ｄ６Ａ杂合子，其余都是野生型纯合子。结论这些基因型的频率和等位基因分布在上海和哈尔滨人群中无差异，符合Ｈａｒｄｙ┐Ｗｅｉｎｂｅｒｇ遗传平衡法则     

GSTM1基因多态现象与原发性肝癌遗传易感性的关系研究

目的探讨谷胱甘肽Ｓ转移酶Ｍ１（ＧＳＴＭ１）基因多态现象与原发性肝癌遗传易感性的关系。方法应用多重ＰＣＲ方法检测５４例肝癌患者（病例组）和１３６例健康人（对照组）的ＧＳＴＭ１空白基因型。结果病例组ＧＳＴＭ１空白基因型频率为７０．３７％，对照组则为４５．５９％，两者非常显著性差异（Ｐ〈０．０１），但２组均不存在性别，年龄差异（Ｐ均〉０．０５）；ＯＲ值为２．８３（９５％ＣＩ值为１．４３－５．４２），ＥＦ     

细胞色素P450 2E1和谷胱甘肽转硫酶P1基因与食管癌易患性

目的研究与致癌物亚硝胺代谢激活有关的细胞色素Ｐ４５０２Ｅ１基因（ＣＹＰ２Ｅ１）,和与致癌物代谢解毒有关的谷胱甘肽转硫酶Ｐ１基因（ＧＳＴＰ１）多型性与食管癌易患性的关系。方法采用病例－对照分子流行病学方法。以ＰＣＲ－ＲＦＬＰ方法分析食管癌、食管上皮重度增生病例,和与其年龄性别配对的正常对照者（各４５例）ＣＹＰ２Ｅ１和ＧＳＴＰ１的基因型。结果ＧＳＴＰ１基因型在病例和对照者中的分布无显著差别,但ＲｓａＩ识别的ＣＹＰ２Ｅ１基因型,在食管癌、食管上皮重度增生病例及其正常对照者中的分布差别显著。ＣＹＰ２Ｅ１突变型基因频率在正常对照组中为５５．６％,显著高于食管上皮重度增生病例（１７．８％）和食管癌病例（２０．０％;χ２＝２０．８,Ｐ＜０．００１）;携带野生型ＣＹＰ２Ｅ１的个体,发生食管上皮重度增生和食管癌的危险性,比携带变异型ＣＹＰ２Ｅ１的个体各高５倍。结论ＣＹＰ２Ｅ１基因是涉及食管癌变早期过程的遗传易患性因素。     

细胞色素P4502E1基因与鼻咽癌易感性分析

目的：为了探讨鼻咽癌的病因发病机理,进一步揭示鼻咽癌的易感因素,本文进行了细胞色素Ｐ４５０２Ｅ１（ＣＹＰ２Ｅ１） 基因多态性与鼻咽癌易感性关系的研究。方法：采用病例－ 对照分子流行病学方法分析１０５ 例鼻咽癌患者和９３ 例正常人体细胞ＣＹＰ２Ｅ１ 基因型。结果： 发现ＲｓａＩ和ＰｓｔＩ识别的ＣＹＰ２Ｅ１ 基因纯合子突变型（Ｃ２／Ｃ２） 在鼻咽癌人群为５－７ ％ ,显著高于正常人群（１－１％ ） 分布（χ２ ＝ ４－８６ ,Ｐ＜ ０－０５） ;携带Ｃ２／Ｃ２ 基因型个体发生鼻咽癌的危险性比携带其它基因型个体高５ 倍左右。结论：ＣＹＰ２Ｅ１ 基因的多态性可能是鼻咽癌易感的因素之一。     

细胞色素p450 2C19基因多态性与胃癌易感性的关系

研究细胞色素ｐ４５０ ２Ｃ１９基历多态性与胃癌易感性的关系。方法：用ＰＣＲ－ＲＦＬＰ法对１００例健康对照者和５０例胃癌患者进行ＣＹＰ２Ｃ１９等位基因多态性分组分析。结果：胃癌患者中ＣＹＰ２Ｃ１９ＰＭ发生率为２８．０％，较正常对照组的１４．０％高，经统计，两组间有显著性差异（χ＾２＝４．３０，Ｐ〈０．０５）。结论：ＣＹＰ２Ｃ１９ＰＭ增加了胃癌发生的危险性，实验结果提示ＣＹＰ２Ｃ１９参与了胃癌致癌物的     

CYP2D6遗传多态性与肺癌易感性关系的研究

目的探讨CYP2D6Ch基因多态性的频率分布,以及与肺癌的遗传易感性关系.方法应用病例-对照研究及PCR-RFLP等技术,检测肺癌及正常对照各50例的CYP2D6Ch基因型,并应用Logistic回归分析基因多态性与肺癌易感性的关系.结果(1)CYP2D6Ch T/T型(突变型)频率在病例组中为36.0%,在对照组中为50.0%;非T/T型(即C/C合并C/T基因型)与肺癌风险临界升高相关(OR=3.06;95%CI=0.94～9.92).(2)对病例组进行相关变量的分层分析后发现,在肺鳞癌,或轻度吸烟组中,CYP2D6Ch非T/T型与肺癌风险升高显著相关(分别为:OR=3.20,CI=1.04～9.85;OR=7.07,CI=1.16～42.85).结论本文提示CYP2D6Ch基因型分布规律与欧美人群差异较大,且T/T型在肺鳞癌或轻度吸烟者中可作为保护因素而降低肺癌的易感性.     

代谢酶CYP2D6基因多态性与肺癌易感性的病例对照研究

背景与目的外源性化合物代谢酶参与环境致癌物在体内的代谢，代谢酶基因多态性被认为与肺癌的易感性相关。本研究的目的是探讨代谢酶细胞色素2D6酶(CYP2D6)基因多态性在四川汉族正常人群和肺癌患者中的分布，以及CYP2D6基因多态性与肺癌易感性的关系。方法应用PCR-RFLP技术检测152例正常人和150例原发性肺癌患者的外周血CYP2D6ch基因型；应用病例对照研究分析CYP2D6ch基因多态性与肺癌易感性的关系。结果(1)CYP2D6ch基因的C和T等位基因在正常人群中分布频率分别为39．5％和60．5％，而肺癌患者中分布频率分别为46．3％和53．7％；两组间C和T等位基因频率比较无显著性差异(P=0．089)。(2)CYP2D6ch等位基因型C／C、C／T、T／T在正常人群中分布频率分别为18．4％、42．1％和39．5％，而在肺癌患者中分布频率分别为22．7％、47．3％和30．0％，两组间比较无显著性差异(P=0．215)。(3)携带CYP2D6ch非T／T等位基因型的个体患肺鳞癌风险是携带T／T等位基因型的2．084倍(95％CI 1．024～4．244，P=0．043)。(4)携带CYP2D6ch非T／T等位基因型的轻度吸烟者患肺癌风险是携带CYP2D6ch T／T等位基因型轻度吸烟者的2．92倍(95％CI1．087～7．828，P=0．033)。结论CYP2D6ch非T／T等位基因型与肺鳞癌风险升高相关，在轻度吸烟人群中，非T／T等位基凶型与肺癌风险升高相关。     

CYP1A1 GSTM1基因多态性和吸烟与肺癌易感性关系的病例对照研究

目的:探讨天津市居民致癌物代谢酶CYP1A1和GSTM1基因多态性对肺癌易感性的影响。方法:利用限制性片断长度多态性-聚合酶链反应(RFLP-PCR)方法检测原发性肺癌患者和健康对照者细胞色素P450酶基因CYP1A1Msp位点和谷胱甘肽硫转移酶基因GSTM1的多态性情况。结果:肺癌组与对照组之间CYP1A1和GSTM1基因型分布差异均存在统计学显著意义(P<0.05)。携带CYP1A1变异基因型或GSTM1阴性基因型的个体患肺癌的危险性增高,比值比(OR)分别达到2.44(1.04～5.81)和1.84(1.03～3.29)。多因素分析结果显示具有CYP1A1变异基因型、GSTM1阴性基因型的吸烟个体患肺癌的风险较大。结论:CYP1A1Msp位点变异基因型和GSTM1阴性基因型可能是肺癌的易感因素,吸烟与肺癌易感基因之间具有协同作用。     

Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung

This study aimed to identify new genetic characteristics contributing to individual susceptibility to smoke-induced lung cancer. Despite functional evidence of a possible role of cytochrome P450 1A2 (CYP1A2) in lung cancer susceptibility, no studies have evaluated the influence of CYP1A2 genotypes on lung cancer risk. We investigated the interaction between CYP1A2-T2467delT (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male smokers) separately for the histological types squamous cell carcinoma (SCC) (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a case-only study design. A significant interaction between CYP1A2-T/delT or delT/delT genotypes and tobacco consumption (pack-years) adjusted for age was evident (OR (95% CI) 7.78 (1.52-42.8)) in the SCC cases who smoked relatively less (< or =33 pack-years, I quartile value), but not in adenocarcinoma and controls. Our results suggest that CYP1A2-T2467delT polymorphism has an important role in lung carcinogenesis, especially SCC, among smokers.     

Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population. METHODS: Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS (and other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke. RESULTS: When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P =. 02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year = ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure. CONCLUSIONS: A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele).     

Genetic polymorphism of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients

Polymorphic changes in the GSTM1, CYP2E1 and the CYP2D6 geneshave been reported to be individually associated with increasedsusceptibility to certain cancers. In the present study, therelationship between genetic polymorphism for these genes anddevelopment of urinary bladder cancer among Egyptian patientswas investigated. Our results indicate that the frequency ofbladder cancer patients with the GSTM1 null genotype is significantlyhigher than that of the normal controls (86.3 and 47.6%, respectively)with an odds ratio (OR) of 6.97 (95% CL = 1.59–30.57,Fisher's exact P = 0.008). In contrast, our investigation failedto demonstrate any difference in the distribution of CYP2E1polymorphism between bladder cancer patients and controls asdetected by PstI restriction fragment length polymorphism (RFLP)analysis. RFLP analysis of the CYP2D6 gene revealed a non-significantincrease in the number of extensive metabolizers (EM) amongthe patients compared to the controls (68 versus 48%). However,the EM genotypes enhances the risk further for individuals harboringthe GSTM1 null genotype as individuals harboring both the EMand the GSTM1 null genotypes have an odds ratio of 14.0 (95%CL = 1.3–151.4, Fisher's exact P = 0.02) compared to individualsharboring the EM and the GSTM1+/+ genotypes. In conclusion,our results indicate that genetic polymorphism, especially inGSTM1 and CYP2D6 could play an important role as host risk factorsfor development of urinary bladder cancer among Egyptians.     

Ethnic susceptibility to lung cancer: differences in CYP2E1, CYP1A1 and GSTM1 genetic polymorphisms between French Caucasian and Chilean populations.

Many investigators have reported an association between genetic polymorphisms of cytochromes P-450 CYP2E1, CYP1A1 or glutathione S-transferase Mu (GSTM1) and susceptibility to lung cancer. However, pronounced interethnic variations have been described in the frequencies of these polymorphisms, especially between Asians and Caucasians. The present study was set up to establish CYP2E1 (c1, c2 and C, D), CYP1A1 (m1, m2 and Ile, Val) and GSTM1 (null) allelic frequencies in Chileans (n = 96) who are an admixture of Native Americans and Caucasians (Spaniards). The rare allele frequencies were found to be 0.15 (c2), 0.21 (C), 0.23 (m2), 0.32 (Val) and 0.21 ('null' genotype). These values are significantly higher than those of Caucasians except for the GSTM1 'null' genotype and suggest differences in susceptibility to lung cancer between both populations.     

GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms in lung cancer patients from an environmentally polluted region of Poland: correlation with lung DNA adduct levels.

The CYP and GST genetic polymorphisms, controlling metabolism of xenobiotics, are considered to influence an individual's susceptibility to environmental and occupational carcinogens and predisposition to cancer. In the study, the effect of the GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms was investigated in relation to PAH-DNA adduct levels in non-tumourous lung tissue from non-small cell lung cancer (NSCLC) patients living in the industrialized region of Upper Silesia, Poland. The level of adducts among smokers was significantly elevated when compared to non-smokers (P = 0.0005). Adduct levels correlated inversely with age of patients (P = 0.00001). The GSTP1 and CYP2D6 polymorphisms had no influence on DNA adduct levels. There was a significant relationship between high adduct levels and the combined GSTM1 (null)/CYP1A1-Ile/Val genotype in the squamous cell carcinoma group (P = 0.028). An elevated number of adducts was found in patients with the GSTM1 (null)/CYP1Al-Ile/Val genotype compared to the GSTM1 (null)/CYP1A1-Ile/Ile carriers (P = 0.043). A higher frequency of the CYP1A1-Ile/Val and GSTM1 (null)/CYP1A1-Ile/Val genotypes was observed in patients with high adduct levels (P = 0.05 and P = 0.009, respectively). A significant prevalence of the GSTM1(null)/CYP1A1-Ile/Val carriers in the adenocarcinoma group was found (P = 0.003). Thus, our findings imply that the GSTMI and CYP1A1 exon 7 polymorphisms may influence PAH-DNA adduct levels in target tissue from NSCLC patients, especially in the squamous cell carcinoma group. Moreover, individuals carrying the GSTM1(null)/CYP1A1-Ile/Val genotype might exhibit a greater predisposition to a peripheral type of lung cancer.     

Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer patients

Polymorphisms in xenobiotic metabolizing enzymes have been implicated in inter-individual and inter-ethnic differences in cancer susceptibilty. Several studies have indicated an association between variant alleles of the human CYP1A1, CYP2E1 and GSTM1 genes and lung cancer. Activity of microsomal epoxide hydrolase (HYL1) has also been associated with lung cancer, and 2 variant alleles causing amino acid substitutions have been described. We have investigated genetic polymorphisms of the CYP1A1, CYP2E1, GSTM1 and HYL1 genes in 76 Chinese lung cancer patients and 122 healthy Chinese subjects. The allele frequency of the CYP1A1*2B allele was 0.21 among lung cancer patients and 0.20 in the reference group, whereas the corresponding values for the CYP1A1*2A allele were 0.34 and 0.36. The CYP2E1*5B and CYP2E1*6 alleles were less frequent among the cancer patients (0.20 and 0.22) compared with healthy subjects (0.25 and 0.26). The frequency distribution of the HYL1*2 allele was 0.49 among lung cancer patients and 0.42 in the reference group, and the corresponding frequencies for the HYL1*3 allele were 0.13 and 0.10. The homozygous GSTM1*0 genotype was found in 64% of lung cancer patients and in 66% of healthy subjects. Among heavy smokers, the frequency was 73%. The differences in the distribution of variant CYP1A1, CYP2E1 and GSTM1 alleles in lung cancer patients and healthy controls were not statistically significant. Our results indicate that the polymorphisms investigated are of minor importance as genetic susceptibility markers for lung cancer in this population. An increased risk for lung cancer in subjects carrying the HYL*3 allele was observed and suggests that polymorphism in this gene might possibly be a susceptibility factor in the Chinese population.     

Interactive effect of genetic polymorphism of glutathione S-transferase M1 and smoking on squamous cell lung cancer risk in Korea

To evaluate the role of the genetic polymorphisms of CYP2E1, GSTM1 and GSTT1, and their interaction with smoking in lung cancer development in Korean males, a hospital-based case-control study was conducted. Histologically confirmed male lung cancer patients (n=171) and male patients with no present or previous history of systemic illness who visited the urology department (n=196) were recruited from Seoul National University Hospital, Korea (1998-1999). CYP2E1 genotypes were determined by PCR-RFLP using RsaI digestion and GSTM1 and T1 genotypes were determined by multiplex PCR. Risks were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) using a logistic regression model adjusting for age and pack-year. Smoking was a significant risk factor for lung cancer (P<0.001). Although genetic polymorphisms of CYP2E1, GSTM1 and T1 were not associated with the overall risk of lung cancer, the GSTM1 null genotype significantly increased the risk of squamous cell lung cancer (OR=1.9, 95% CI=1.04-3.60). An interactive effect between the GSTM1 null genotype and smoking was observed (P=0.04). These results suggest that the GSTM1 null genotype is associated with squamous cell lung cancer and modifies the effect of smoking on squamous cell lung cancer development in Korean males.