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     

CYP2D6、GSTM1遗传多态性与肺癌易感性关系

目的探讨中国汉族广东籍人群中ＣＹＰ２Ｄ６、ＧＳＴＭ１的遗传多态性与肺癌易感性关系。方法采用病例—对照研究方法,用ＰＣＲ检测ＣＹＰ２Ｄ６、ＧＳＴＭ１的基因型,限制性酶切电泳鉴定ＣＹＰ２Ｄ６点突变。结果病例组与对照组间未发现ＣＹＰ２Ｄ６多态性分布差异,而ＧＳＴＭ１多态性存在分布差异,病例组为５８．７％,对照组为３５．７％（Ｐ＜０．０５）,ＯＲ值为２．５６（１．１１－２．４４）。结论ＣＹＰ２Ｄ６Ｇ－Ａ突变与肺癌易感性未见有联系,ＧＳＴＭ１－／－型个体患肺癌易感性增高     

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。     

卵巢癌MDR1基因表达与近期化疗效果

目的　研究卵巢癌ＭＤＲ１ 基因表达对化疗的影响。　方法　应用免疫组织化学（ＡＢＣ） 法及改进的逆转录聚合酶链反应（ＲＴＰＣＲ）分别检测ＰＧＰ和ＭＤＲ１ 基因ｍ ＲＮＡ 的表达水平。　结果　４９ 例卵巢癌中用ＡＢＣ法检测ＰＧＰ表达的阳性率为４２８％ ,其中有化疗史的阳性率为３６０％ ;无化疗史的为５００ ％ （ Ｐ＞ ００５）。ＰＧＰ染色阴性的近期化疗有效率为５３６ ％ ,而染色阳性的为１４３ ％ （Ｐ＜ ００５） 。有３７ 例卵巢癌用改进的ＲＴＰＣＲ 检测ＭＤＲ１ 基因ｍ ＲＮＡ 表达的阳性率为７０３ ％ 。有化疗史的阳性率为９５２％ ;而无化疗史的阳性率为３７５ ％（ Ｐ＜０００１） 。ＭＤＲ１ 基因ｍＲＮＡ表达阴性的近期化疗有效率为８１８ ％ ,而表达阳性的为２３１％ （Ｐ＜ ０００５）。此同样３７ 例卵巢癌免疫组化结果并未见与化疗史相关,但仍发现与近期疗效存在相关性。　结论　ＭＤＲ１ 基因表达与卵巢癌化疗密切相关,ＰＧＰ／ ＭＤＲ１ ｍＲＮＡ 有可能作为预测卵巢癌化疗效果的一项指标。改进ＲＴＰＣＲ 方法适用于临床耐药性检测。     

国外动态

ＣＹＰ１Ａ１基因多态性与上皮性卵巢肿瘤土耳其Ｈａｃｅｔｔｅｐｅ大学医学院遗传学科的ＡｋｔａｓＤ等通过对土耳其患有上皮性卵巢肿瘤病人和配对的人群的ＣＹＰ１Ａ１基因多态性进行联合评估。利用ＰＣＲ技术特异性等位基因ＣＹＰ１Ａ１的多态性 ,在１１７个上皮性卵巢肿瘤病人和２０２个配对的人 ,对基因外显子７进行了分析。证实在患上皮性卵巢肿瘤的病人中ＣＹＰ１Ａ１Ｉｌｅ／Ｖａｌ基因型显著增加（ＯＲ５．７,９５%ＣＩ３．３４～９．７６）。而且在统计学上有显著意义。在良性肿瘤Ｉｌｅ／Ｖａｌ和Ｖａｌ／Ｖａｌ基因型频率（分别…     

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。     

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     

晚期非小细胞肺癌ＧＳＴＰ１、ＸＲＣＣ１基因多态性与铂类药物疗效的关系

目的　探讨谷胱甘肽Ｓ转移酶Ｐ１（ＧＳＴＰ１）和Ｘ线修复交叉互补基因１（ＸＲＣＣ１）基因多态性与晚期非小细胞肺癌（ＮＳＣＬＣ）患者化疗疗效的关系。方法　经病理学确诊的晚期ＮＳＣＬＣ患者９４例,化疗前取静脉血采用ＤＮＡ测序法检测ＧＳＴＰ１和ＸＲＣＣ１基因多态性,给予铂类为主方案化疗（顺铂７５ｍｇ／ｍ２,ｄ１）,２～３周期后评价疗效,记录疾病进展时间（ＴＴＰ）,分析ＧＳＴＰ１和ＸＲＣＣ１基因多态性与化疗疗效的关系。结果　在９４例晚期ＮＳＣＬＣ患者中,携带ＧＳＴＰ１Ａ／Ａ基因４９例,Ｇ／Ａ基因３４例,Ｇ／Ｇ基因１１例;携带ＸＲＣＣ１Ｇ／Ｇ基因５２例,Ｇ／Ａ基因３５例,Ａ／Ａ基因７例,均符合Ｈａｒｄｙ Ｗｅｉｎｂｅｒｇ遗传平衡规律。携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ基因型的有效率为４４.４４％,显著高于Ａ／Ａ基因型的２０.４１％（Ｐ＜０.０５）;携带ＸＲＣＣ１Ｇ／Ｇ基因型与Ｇ／Ａ＋Ａ／Ａ基因型的有效率差异无统计学意义（Ｐ＞０.０５）;两基因多态性的联合分析显示,同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型的有效率最高,为６６.６７％,但未见统计学意义（Ｐ＞０.０５）。９４例患者中有５例失访,８９例患者的中位ＴＴＰ为６.５个月,携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ基因型的中位ＴＴＰ为８.０个月,Ａ／Ａ基因型为６.０个月,两者差异有统计学意义（Ｐ＜０.０１）;携带ＸＲＣＣ１Ｇ／Ｇ基因型的中位ＴＴＰ为７.０个月,Ｇ／Ａ＋Ａ／Ａ基因型为６.５个月,两者差异无统计学意义（Ｐ＞０.０５）;联合分析显示同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型的中位ＴＴＰ最长,为９.５个月,各组间差异有统计学意义（Ｐ＜０.０１）。结论　ＧＳＴＰ１基因多态性与晚期ＮＳＣＬＣ患者接受铂类为主化疗方案的疗效及预后有关,同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型患者的化疗有效率高,预后好,但因样本量较小,需要扩大样本进一步验证。     

非吸烟女性肺癌患者细胞色素P4501A1和GSTM1的基因型

目的分析非吸烟肺癌女性与健康女性的细胞色素Ｐ４５０１Ａ１和ＧＳＴＭ１的基因型。方法比较上海和哈尔滨二地的非吸烟肺癌女性各１００例和８２例，以及年龄配对的健康女性各９５和８９例。用酚┐氯仿法提取白细胞中的ＤＮＡ，分析细胞色素Ｐ４５０１Ａ１和ＧＳＴＭ１的基因型。结果两组基因型在病例和对照间以及两地间无差异。结论虽然在上海人群中ＣＹＰ１Ａ１突变型纯合子合并ＧＳＴＭ１缺失的ＯＲ值可达６．５９，但未达统计学显著性     

Susceptibility of Lung Cancer with Polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 Genotypes in the Population of Inner Mongolia Region

Background: To study the relationship of susceptibility to lung cancer with the gene polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1, GSTP1 and smoking status in Han and Mongolian populations of Inner Mongolia, an autonomous region of China. Materials and Methods: PCR-RFLP, allele-specific and multiplexPCR were employed to identify the genotypes of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 in a case-control study of 322 lung cancer patients diagnosed by bronchoscopy and 456 controls free of malignancy. Results: There is a significant difference in genotypic frequency of GSTT1 of healthy Mongolian and Han subjects. A statistically prominent association was found between CYP1A1 Msp1 (vt/vt) (OR=4.055, 95%CI:2.107-7.578, p=0.000), GSTM1 (-) (OR=2.290, 95%CI:1.467-3.573, p=0.000) and lung cancer in Mongolians. Similarly, in the Han population, CYP1A1 Msp1 (vt/vt) (OR=3.194, 95%CI:1.893-5.390, p=0.000) and GSTM1 (-) (OR=1.884, 95%CI:1.284-2.762, p=0.001) carriers also had an elevated risk of lung cancer. The smokers were more susceptibleto lung cancer 2.144 fold and 1.631 fold than non-smokers in Mongolian and Han populations, respectively. The mokers who carried with CYP1A1 Msp1 (wt/vt+vt/vt), exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB),and GSTT1 (-) respectively were found all to have a high risk of lung cancer. Conclusions: CYP1A1 Msp1 (vt/vt) and GSTM1 (-) are risk factors of lung cancer in Han and Mongolian population in the Inner Mongolia egion. The smokers with CYP1A1 Msp1 (wt/vt+vt/vt), CYP1A1 exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3(AB+BB), and GSTT1 (-) genotypes, respectively, are at elevated risk of lung cancer.     

58. Susceptibility to lung cancer is associated with genetic polymorphisms of CYP1A1、GSTM1

Objective: To investigate the association of lung cancer susceptibility with genetic Polymorphism of CYP1A1 and GSTM1. Methods: The study was conducted on 65 lung cancer cases and 60 no-cancer controls. The genetic polymorphism both CYP1A1 and GSTM1 were performed in cancer tissues of all patients and peripheral blood leukocytes of no-cancer controls. First by RFLP-PCR, then after incubating with restriction enzyme Ncol and Hinfl. Results: ①There were no significant differences in the frequency distribution of CYP1A1 polymorphisms between lung cancer patients and controls, but the frequency of CYP1A1(Val/Val) was significant higher than that controls (P<0.05). ②If OR for CYP1A1 (Ile/Ile) genotype was 1.0, the OR of CYP1A1 (Ile/VaL)、CYP1A1 (Val/Val) was 1.68 (95%CI, 0.79～3.59) and 3.2 (95%CI, 1.06～10.26), respectively. ③The significant difference were observed that GSTM1(-) became markedly expressed (63.1%, 41/65) in elung cancer patients than in the corresponding controls (45%, 27/60) (P<0.05), OR was 2.09 (95%CI, 1.02～4.26); ④When analysis combined CYP1A1 and GSTM1 genotype, we found that individual who take along CYP1A1 (Ile/Ile)/GSTM1 (-) or CYP1A1 (Ile/Val+Val/Val)/GSTM1 (+) genotype had higher odds ratio than CYP1A1 (Ile/Ile)/GSTM1 (+) genotype, the OR was 3.82 (95%CI, 1.27～11.45) and 3.5 (95%CI 1.18～10.41), respectively, but the CYP1A1 (Val/Val) / GSTM1 (-) genotype was the hightest odds ratio, the OR was 10.5 (95%CI, 1.70～64.73). ⑤We observed that the individual who carry CYP1A1(Val/Val) genotype can increased risk of squamous cell carcinoma of lung (P<0.05), OR was 2.75 (95%CI, 1.24～6.17), there was no significant associated of pathologic with GSTM1 genotype. ⑥Stratified analysis suggested an interaction between cigarettes smoking and CYP1A1 (Ile/Val+Val/Val)、GSTM1 (-) genotype. Conclusion: ①The individuals who carried genotype of CYP1A1 (Val/Val) and GSTM1 (-) were susceptible to lung cancer. ②the individuals who carried CYP1A1 (Ile/Ile) /GSTM1 (-) or CYP1A1 (Ile/Val+Val/Val) /GSTM1 (+) genotype with higher risk of developing lung cancer than that CYP1A1 (Ile/Ile)/GSTM1 (+) genotype. ③There were interaction between smoking and CYP1A1 (Ile/Val+Val/Val)、GSTM1 (-)     

p53 mutations of lung cancer are not significantly affected by CYP1A1 or GSTM1 polymorphisms

Cytochrome p4501A1 gene (CYP1A1) and glutathione S-transferase mu gene (GSTM1) are involved in the metabolic activation or detoxification of environmental carcinogens including benzo[a]pyrene in tobacco smoke. Individuals with both Val/Val and C type of CYP1A1 (CYP1A1; Val/Val and CYP1A1; C) or homozygous null (-/-) genotype of GSTM1 gene (GSTM1; -/-) show increased susceptibility to lung cancer. The incidence of p53 gene mutations are related to the smoking index of the lung cancer patients. Therefore we determined genotypes of these enzymes and screened p53 gene mutations in 123 non-small cell lung cancer (NSCLC) patients. p53 gene mutations were found in 35% (43/123) of the patients. The incidence of p53 gene mutation CYP1A1; Val/Val (60.0%), CYP1A1; C (50.0%) tended to be higher than those of CYPIAI; Ile/Ile and Ile/Val (40.4%) or CYP1A1; A and B (40.5%). We conclude that the incidence of the p53 mutations does not seem to be significantly affected by only CYP1A1 or GSTM1 polymorphisms in lung cancer patients.     

Lung cancer susceptibility and polymorphisms of glutathione-S-transferase genes in Hong Kong

OBJECTIVE: To study the potential role of genetic polymorphisms of glutathione-S-transferases GSTM1, GSTT1 and GSTP1 in susceptibility to lung cancer in Hong Kong Chinese. METHODS: 229 consecutive incident patients with a histological diagnosis of lung cancer from a regional hospital and 197 healthy population-based controls were recruited for this study between July 1999 and June 2001. Genetic polymorphisms of GSTT1 and GSTM1 were determined using PCR-based technique. RESULTS: The frequencies of GSTT1 and GSTM1 null genotypes were 51.8 and 59.4% in healthy controls and 63 and 54.7%, respectively, in lung cancer patients. GSTP1 Val105/Val105 genotype was found in only 1% of healthy controls. The risk for lung cancer with GSTT1 null genotype was significantly higher, adjusted odds ratio (OR) 1.69, 95% confidence interval (CI) 1.12-2.56, compared with those with the GSTT1 genotype; the increase in risk was found only in non-smokers. GSTM1 null genotype, combined GSTT1 and GSTM1 null genotype and GSTP1 Val105/Val105 genotype did not confer any increase risk for lung cancer. CONCLUSION: GSTT1 null genotype is associated with an increased risk for lung cancer in non-smoking Chinese in Hong Kong.     

CYP1A1与GSTM1的多态性与原发性肝癌遗传易感性的关系研究

目的 :探讨细胞色素P4 5 0 1A1(cytochromeP4 5 0 1A1,CYP1A1)与谷胱苷肽S -转移酶M1(glu tathioneS transferaseM 1,GSTM 1)的多态性与原发性肝癌遗传易感性的关系。方法 :应用等位特异PCR和多重PCR技术对 5 2例原发性肝癌患者和 10 0名健康对照的CYP1A1和GSTM 1多态性进行分析。结果 :肝癌患者CYP1A1第 7外显子 4 62Val的等位变异频率为 0 .4 6,显著高于正常对照的变异频率(0 .2 2 ) ,病例组GSTM1的纯合型缺失频率 (0 .65 )也显著高于对照组 (0 .4 1) ,携带有CYP1A1Val/Val纯合变异和GSTM1纯合缺失基因型的人患肝癌的风险大大增加 ,前者的比值比 (oddsratio ,OR)及 95 %可信区间 (confidenceinterval,95 %CI)为 4 .13(1.2 8～ 13.35 ) ,后者的OR值及 95 %CI为 2 .72 (1.35～5 .4 6) ,二者联合OR值及 95 %CI为 8.5 0 (1.74～ 4 1.5 0 )。结论 :CYP1A1和GSTM 1的多态是原发性肝癌的遗传易感因素 ,二者的等位变异增加了患肝癌的风险     

GSTM1和CYP1A1基因多态性与宫颈癌发生及发展的相关性

目的:探讨谷胱苷肽硫转移酶M1（GSTM1）和CYP1A1 Exon7基因多态性与宫颈癌发生发展的关系。方法:选取2013年5月至2015年5月我院收治的宫颈癌患者184例为宫颈癌组,203例进行体检的健康人群为参照组。用限制性片段长度多态性-聚合酶链反应（RFLP-PCR）检测所有受试者GSTM1和CYP1A1 Exon7基因型;记录无进展生存期（PFS）,并随访观察生存和死亡情况。结果:GSTM1分为野生型（wt）和突变缺失型（null）,CYP1A1 Exon7野生型为Ⅱe/Ⅱe,突变型包括突变纯合型（Val/Val）、突变杂合型（Ⅱe/Val）。宫颈癌组携带GSTM1突变型基因型比例与参照组间比较,差异无统计学意义（P＞0.05）;宫颈癌组携带CYP1A1 Exon7突变型基因型比例显著高于参照组（P＜0.05）,且携带突变型基因型个体患宫颈癌的风险是携带野生型基因型个体的2.333倍。GSTM1、CYP1A1 Exon7基因型与宫颈癌患者年龄、病理分期、肿瘤分化程度、肿瘤直径及淋巴结转移均无关（P＞0.05）,与患者病理类型有关（P＜0.05）。GSTM1、CYP1A1 Exon7突变型宫颈癌患者PFS中位数与野生型患者比较,差异均无统计学意义（P＞0.05）。GSTM1、CYP1A1 Exon7突变型宫颈癌患者基因型与宫颈癌患者预后无关（P＞0.05）。结论:GSTM1及CYP1A1 Exon7基因多态性是宫颈癌发生发展的危险因素,尤其是CYP1A1 Exon7突变型,为预防宫颈癌提供依据。     

CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women

Polymorphisms in metabolic genes encoding phase I and phase II enzymes are thought to modulate the risk of lung cancer via changes in enzymatic activity. Recently, the effect of these metabolic enzymes and their interaction with environmental factors has been studied in both smokers and also never-smokers, since never-smokers are a good model in which to study genetic susceptibility at low-dose carcinogen exposure. Here, we investigated the association of CYP1A1 Ile462Val, CYP1B1 Leu432Val, GSTP1 Ile105Val, MPO G-463A polymorphisms and lung cancer risk in never-smoking Korean women. In this case-control study of 213 lung cancer patients and 213 age-matched healthy controls, we found that carrying one variant allele of the CYP1A1 Ile462Val polymorphism was associated with a significantly decreased risk of lung adenocarcinoma (adjusted odds ratio (OR)=0.63; 95% confidence interval (CI), 0.41-0.99). Furthermore, the combination of risk genotypes of CYP1B1 Leu432Val with CYP1A1 Ile462Val was associated with the risk of lung adenocarcinoma (adjusted OR=2.16; 95% CI, 1.02-4.57) as well as overall lung cancer (adjusted OR=2.23; 95% CI 1.01-4.89). The polymorphisms of GSTP1 Ile105Val and MPO G-463A showed no significant association with lung cancer. Theses results suggest that the CYP1A1 Ile462Val polymorphism is associated with a reduced risk of lung adenocarcinoma in never-smoking Korean women, whereas specific combinations of variant genotypes for metabolic enzymes increase lung cancer risk considerably.     

Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer.

Sequence variation in the GSTM1, GSTT1, GSTP1, and CYP1A1 genes may potentially alter susceptibility to head and neck cancers, although evidence from previous studies has not been consistent. To explore these associations, we conducted a meta-analysis of 31 published case-control studies (4635 cases and 5770 controls) and a pooled analysis of original data from nine published and two unpublished case-control studies (2334 cases and 2766 controls). In the meta-analysis, the summary odds ratios (ORs) for head and neck cancer were 1.23 [95% confidence interval (95% CI), 1.06-1.42] for the GSTM1 null genotype, 1.17 (95% CI, 0.98-1.40) for the GSTT1 null genotype, 1.10 (95% CI, 0.92-1.31) for carrying the GSTP1 Val105 allele, and 1.35 (95% CI, 0.95-1.82) for carrying the CYP1A1 Val462 allele. The pooled analysis ORs were 1.32 (95% CI, 1.07-1.62) for the GSTM1 null genotype, 1.25 (95% CI, 1.00-1.57) for the GSTT1 null genotype, 1.15 (95% CI, 0.86-1.53) for carrying the GSTP1 Val105 allele, and 0.98 (95% CI, 0.75-1.29) for carrying the CYP1A1 Val462 allele. Increasing risk of head and neck cancer was observed with inheritance of increasing numbers of modest risk genotypes at the three GST loci (P for trend = 0.04), with the combination of carrying the GSTM1 null, GSTT1 null, and GSTP1 Val105 alleles conferring an OR of 2.06 (95% CI, 1.11-3.81). In conclusion, both the meta- and pooled analysis support modest associations of GSTM1 and GSTT1 genotypes with head and neck cancer risk, and our pooled analysis supports the notion of greater risk when genotypes at multiple GST loci are considered in a multigenic model.     

Gluthatione-S-transferase T1-null Genotype Predisposes Adults to Acute Promyelocytic Leukemia; a Case-Control Study

Polymorphisms of glutathione S-transferase (GST) proteins are correlated with elevated risk of many cancersincluding hematologic malignancies. Particularly concerning acute promyelocytic leukemia (APL), the studies onassociation between GSTM1, GSTT1 and GSTP1 and the disease predisposition are scarce and contradictory. Theaim of this study was to examine whether polymorphic variations in GST confer susceptibility to APL. GSTM1and GSTT1 null and GSTP1 Ile105Val alleles were determined using polymerase chain reaction (PCR) andPCR-RFLP, respectively, in 114 APL patients and 99 healthy controls. Frequency of GSTT1 null and GSTM1null genotypes were higher in APL group which it was statistically significant for GSTT1 null (p< 0.01). TheGSTM1 null and GSTT1 null conferred a 1.36-fold (OR= 1.36, 95% CI = 0.79-2.33, p= 0.18) and 2.14-fold (OR=2.14; 95% CI: 1.18-3.92, p= 0.013) increase in risk of APL, respectively, relative to the presence of the GSTM1 orGSTT1 genes. GSTP1 Ile105/Val105 and Val105/Val105 genotypes showed no increase in the risk of APL (OR=0.94; 95% CI: 0.52-1.67 and OR= 1.12; 95% CI: 0.48-2.60, respectively). Our results suggest that GSTT1 nullgenotype may be associated with increased risk of APL.     

CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis

Genetic polymorphisms of cytochrome p450 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes are thought to have significant effects on the metabolism of environmental carcinogens and thus on cancer risk, but the reported results are not always consistent. In this meta-analysis, we assessed reported studies of associations between polymorphisms of these two genes and risk of lung cancer in Chinese populations. Through a systematic literature search for publications between 1989 and 2006, we summarized the data from 46 studies on polymorphisms of MspI and exon7-Val of CYP1A1 and GSTM1 and lung cancer risk in Chinese populations, and found that compared with the wild-type homozygous genotype (type A), lung cancer risk for the combined variant genotypes (types B and C) was 1.34-fold (95% confidence interval [CI]=1.08-1.67) (Z=2.64, P=0.008); the risk for the combined variant genotypes (Ile/Val and Val/Val) of CYP1A1 exon7 was 1.61-fold (95% CI=1.24-2.08) (Z=3.62, P<0.001), compared with the Ile/Ile genotype; and that the risk for the GSTM1 null genotype was 1.54-fold (95% CI=1.31-1.80) (Z=5.32, P<0.001), compared with the GSTM1 present genotype. Therefore, in 46 published studies in Chinese populations, we found evidence of an association between the CYP1A1 variant and GSTM1 null genotypes and increased risk of lung cancer.