Study on the relationship between GSTM1, GSTT1 gene polymorphisms and arsenic methylation level

OBJECTIVE: To investigate the relationship between genetic polymorphisms of GSTT1, GSTM1 and arsenic methylation level. METHODS: 247 residents in an industrial arsenic polluted village were randomly selected as subjects. The genetic polymorphisms of GSTM1 and GSTT1 were detected by multiple PCR method. Urinary inorganic arsenic (iAs), monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) concentrations were determined by ion chromatogram combined with HG-AFS. RESULTS: No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTT1 positive genotype and the individuals with GSTT1 null genotype. No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTM1 positive genotype and the individuals with GSTM1 null genotype. And no significant differences in the relative proportion of urinary iAs, MMA and DMA was observed among the individuals with different GSTM1 and GSTT1 associated genotype. CONCLUSION: The polymorphisms of GSTT1 and GSTM1 were not associated with arsenic metabolism level in the studied population.     

GSTT1和GSTM1基因多态性与人体砷甲基化代谢水平关系探讨

目的探讨GSTT1、GSTM1基因多态性与人体砷甲基化代谢水平之间的关系。方法选择某工业性砷污染区的247名成年常住居民为研究对象。采用多重PCR法检测GSTM1和GSTT1基因多态性。离子色谱氢化物发生原子荧光法(IC-HG-AFS)测定尿中无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)。结果GSTT1缺失基因型人群与GSTT1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。GSTM1缺失基因型人群与GSTM1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。四组不同GSTT1和GSTM1联合基因型人群尿中iAs比例、DMA比例和MMA比例相比较,四组间差异也均无统计学意义(P>0.05)。结论本研究未发现GSTT1、GSTM1基因多态性与砷代谢水平之间存在显著关联。     

GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening

Genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione S-transferases (GSTM1, GSTT1, and GSTP1) superfamily have been associated with an increased risk for breast cancer (BC). Considering the high incidence of BC in the city of Porto Alegre in southern Brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in GSTM1, GSTT1, and GSTP1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. Molecular tests were performed using the multiplex polymerase chain reaction (PCR) for GSTM1 and GSTT1, and quantitative PCR for GSTP1 polymorphisms. Overall, the frequencies of GSTM1 and GSTT1 null genotypes were 45% and 21%, respectively. For GSTP1 polymorphism, genotypic frequencies were 44% for the Ile/Ile genotype, 44% for the Ile/Val genotype, and 12% for Val/Val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. There was a statistically significant association between the combined GSTM1 and GSTT1 null genotypes (M-/T-) and mammographic density in post menopausal women (p = 0.031). When the GSTT1 null (T-) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). These findings suggest an association of GSTM1 and GSTT1 null genotypes with mammographic density.     

GSTM1、GSTT1及GSTP1基因多态性与子宫内膜异位症的相关性研究

目的:探讨唐山地区汉族妇女谷胱甘肽S-转移酶超家族成员GSTM1、GSTT1及GSTP1基因多态性与子宫内膜异位症遗传易感性的关系。方法:采用MD-PCR和RFLP-PCR技术检测94例子宫内膜异位症患者和102例对照妇女的GSTM1、GSTT1及GSTP1的基因型。结果:GSTM1、GSTT1、GSTP1各基因型在病例组和对照组中的分布,差异无统计学意义(P>0.05),携带AG基因型个体患病的风险是携带AA基因型个体的1.74倍,GSTP1各等位基因在各组中的分布无统计学差异。结论:未发现GSTM1、GSTT1、GSTP1基因多态性与子宫内膜异位症有关,尚不能认为GSTM1和GSTT1缺失基因型是子宫内膜异位症的易感基因型。     

长期高砷暴露人群砷甲基化与皮肤损害关系的研究

目的探讨长期高砷暴露人群砷代谢差异与砷致皮肤损害之间的关系。方法随机选取某砷污染村庄常住居民327名,进行问卷调查和体格检查。二乙基二硫代氨基甲酸银比色法检测发总砷含量,离子色谱氢化物发生原子荧光法测定尿中四种砷代谢形态。结果发砷含量总体较高,但不同程度皮肤损害的4组间发砷含量差异无显著性;尿中DMA和MMA浓度随着年龄增加有上升的趋势,且与皮肤损害程度呈显著正相关,而无机砷浓度与皮肤损害未见显著相关;重度组人群尿中MMA相对比例显著高于其它3组,而重度组DMA/MMA比值显著低于对照组和轻度组;MMA比例与皮肤损害程度呈显著正相关,DMA/MMA比值与皮肤损害程度呈显著负相关;男性对砷的蓄积能力高于女性,但对砷的甲基化能力低于女性;40岁以上人群对砷的甲基化能力高于40岁以下成人;吸烟者和饮酒者对砷的甲基化代谢水平分别低于非吸烟者和非饮酒者。结论砷在人体内的甲基化代谢水平受性别、年龄、吸烟和饮酒等多因素影响;砷致皮肤损伤程度与砷在体内的甲基化程度有关。     

GSTM1及GSTT1和GSTP1基因多态性对尿中1-羟基芘水平的影响

目的 研究GSTM1、GSTT1和GSTP1基因多态性对多环芳烃接触工人尿中1-羟基芘(1-OHP)水平的影响.方法 分别选取2个炼焦厂共447名多环芳烃职业接触工人(接触组)和某线材厂220名非职业接触工人(对照组)作为研究对象,采用高效液相色谱法测定尿中1-OHP水平,采用线性回归统计模型分析GSTM1和GSTT1缺失型及GSTP1 I105V位点的多态性对不同人群尿中1-OHP水平的修饰作用.结果 接触组工人尿中1-OHP浓度为4.61 μmol/mol Cr,明显高于对照组(0.34μmol/mol Cr),差异有统计学意义(P＜0.05).接触类别和吸烟分别是影响尿中1-OHP水平的主要因素,在控制各混杂因素的影响后,线性回归分析显示,接触组尿中1-OHP水平和GSTP1 I105V位点多态性有关(单基因分析,P=0.012;多基因分析,P=0.011),对总体样本,单基因模型和多基因模型均显示,尿中1-OHP水平可能和GSTT1缺失型多态有关(P=0.055),多基因交互作用分析显示,GSTT1和GSTP1基因多态对接触组尿中1-OHP水平具有交互作用.结论 谷胱甘肽硫转移酶(GSTs)基因的多态性对接触多环芳烃工人尿中1-OHP水平有影响.

Abstract：

Objective To investigate the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene (1-OHP) excretions in workers under different exposure levels. Methods Four hundred and forty-seven occupationally exposed workers from two coking plants and 220 control workers from a wire rod plant were genotyped to analyze the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-OHP excretions. Results The urinary 1-OHP concentration in exposed group was much higher than that in control group (4.61 vs 0.34 μmol/mol Cr, P＜0.05). Occupational exposure levels and cigarette smoking were of the dominating factors affecting 1-OHP excretions in urine. After controlling potential confounders, decreased excretion of urinary 1-OHP was associated with GSTP1 I105V AG + GG genotype in coke oven workers (single-gene model, P=0.012; multi-gene model, P=0.011 ) and with GSTT1 null type in the analysis including all subjects (P=0.055 in both single-gene and multi-gene models). GSTT1 and GSTP1 were interacted on the urinary concentrations of 1-OHP. Conclusion Urinary 1-OHP concentrations can be modified by GSTM1, GSTT1 and GSTP1 gene polymorphisms, indicating that these genes are involved in the metabolism of polycyclic aromatic hydrocarbons.     

谷胱甘肽-S-转移酶基因多态与原发型肝癌的Meta分析

目的：探索谷胱甘肽-S-转移酶（GSTM1、GSTT1、GSTP1）基因多态与原发型肝癌遗传易患性的关系。方法：采用Meta分析方法对国内外1994--2004年关于谷胱甘肽-S-转移酶基因多态与原发型肝癌易患性的研究文献进行综合定量分析。结果：共收集相关文献18篇，累计病例1407例，对照2044例。GSTM1空白基因型可能与原发性肝癌有关，OR值为1．40（95％CI：1．22-1．62）；GSTM1和GSTT1中至少有一个空白基因型的OR值为2．05（95CI：％1．14-3．67），亦提示可能与原发型肝癌的遗传易患性有关；而GSTT1空白基因型、GSTP1突变基因型未显示与原发型肝癌相关，合并的OR值分别为1．13（95％CI：0．77-1．65）和0．68（95％CI：0．47～0．99）。结论：谷胱甘肽-S-转移酶基因多态与原发性肝癌遗传易患性的关系各有不同，GSTM1单项空白基因和GSTM1、GSTT1混合空白基因与原发性肝癌有统计学联系，可能是原发性肝癌的易患因素；GSTT1空白基因型与原发性肝癌未显示有统计学联系，而GSTP1的突变基因型可能是原发性肝癌的保护因素。     

NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒的遗传易感性

目的探讨NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒遗传易感性之间的关系。方法选择100名慢性苯中毒病例为病例组及90名同期接苯但无苯中毒表现的同工种工人为对照组,应用PCR-RFLP及多重PCR方法判定NQO1、GSTT1和GSTM1基因型。结果携带NQO1C609TT/T基因型(纯合突变型)个体发生苯中毒的危险性是具有C/T基因型(杂合型)和C/C基因型(野生型)个体的2.82倍(95%CI1.42～5.58,P<0.05),是具有C/C基因型(野生型)个体的2.94倍(95%CI1.25～6.90,P<0.05);携带GSTT1缺失(null)基因型个体发生苯中毒的危险性是具GSTT1非缺失(non-null)基因型个体的1.91倍(95%CI1.05～3.45,P<0.05),未发现GSTM1基因型与苯中毒的关系。同时携带NQO1C609TT/T基因型、GSTT1缺失、GSTM1缺失任何两种基因型的个体发生苯中毒的危险性均高于同时携带野生型及非缺失基因型的个体;并且同时携带NQO1C609TT/T基因型、GSTT1缺失与GSTM1缺失个体接苯时发生苯中毒的危险性最高,是NQO1C609TC/T基因型和C/C基因型、GSTT1非缺失型(non-null)与GSTM1非缺失型(non-null)个体的20.41倍(95%CI3.79～111.11,P<0.01)。结论基因之间的交互作用在苯中毒的发生中起重要作用。同时携带NQO1C609TT/T基因型、GSTT1缺失基因型和GSTM1缺失基因型个体发生苯中毒的风险最     

Maternal smoking, genetic variation of glutathione s-transferases, and risk for orofacial clefts

BACKGROUND: Maternal smoking is a known risk factor for orofacial clefts. We investigated whether risk is greater among offspring who lack the genetic capacity to produce glutathione S-transferase enzymes relevant to detoxification of chemicals in cigarette smoke. METHODS: Using a population-based case-control design, we genotyped 423 California infants with an isolated cleft and 294 nonmalformed controls for null variants of the glutathione S-transferases GSTT1 and GSTM1. RESULTS: If a mother smoked during pregnancy and her fetus was homozygous null for GSTT1, the risk of isolated cleft lip with or without cleft palate was tripled (odds ratio = 2.9; 95% confidence interval = 1.2-7.2). For fetuses who were homozygous null for GSTM1 and whose mothers smoked >/=20 cigarettes per day, we found nearly a 7-fold increased risk (6.8; 0.82-57). Combined absence of GSTM1 and GSTT1 enzymes among the offspring of smoking mothers was associated with a nearly 6-fold increased risk for cleft lip (6.3; 1.3-42). A similar increased risk for cleft palate was associated with absence of GSTM1, but not for absence of GSTT1. CONCLUSIONS: Maternal smoking during pregnancy increases risks for clefts among fetuses lacking enzymes involved in the detoxification of tobacco-derived chemicals.     

GSTT1 genotype modifies the association between cruciferous vegetable intake and the risk of myocardial infarction

BACKGROUND: Cruciferous vegetables are a major dietary source of isothiocyanates that may protect against coronary heart disease. Isothiocyanates induce glutathione S-transferases (GSTs), polymorphic genes that code for enzymes that conjugate isothiocyanates, as well as mutagens and reactive oxygen species, to make them more readily excretable. OBJECTIVE: The objective of the study was to determine whether GST genotypes modify the association between cruciferous vegetable intake and the risk of myocardial infarction (MI). DESIGN: Cases (n = 2042) with a first acute nonfatal MI and population-based controls (n = 2042) living in Costa Rica, who were matched for age, sex, and area of residence, were genotyped for a deletion polymorphism in GSTM1 and GSTT1 and an Ile105Val substitution in GSTP1. Cruciferous vegetable intake and smoking status were determined by questionnaire. Odds ratios (ORs) and 95% CIs for MI were estimated by unconditional logistic regression. RESULTS: Compared with the lowest tertile of cruciferous vegetable intake, the highest tertile was associated with a lower risk of MI among persons with the functional GSTT1*1 allele (OR: 0.70; 95% CI: 0.58, 0.84) but not among those with the GSTT1*0*0 genotype (OR: 1.23; 95% CI: 0.83, 1.82) (P = 0.006 for interaction). This protective effect among those with the GSTT1*1 allele was greater for current smokers (OR: 0.54; 95% CI: 0.36, 0.79) than for nonsmokers. GSTP1 and GSTM1 did not modify the association between cruciferous vegetable intake and MI. CONCLUSIONS: Consumption of cruciferous vegetables was associated with a lower risk of MI among those with a functional GSTT1*1 allele, which suggests that compounds that are detoxified by this enzyme contribute to the risk of MI.     

The role of polymorphisms of glutathione S-transferases GSTM1, M3, P1, T1 and A1 in susceptibility to alcoholic liver disease

AIMS AND METHODS: Oxidant stress is proposed to be an important pathogenic factor in liver damage related to alcohol. The glutathione S-transferases (GSTs) are a group of polymorphic enzymes that are important in protection against oxidant stress. As there is evidence for genetic susceptibility to alcohol-related liver disease we have compared the frequency of polymorphisms of GSTM1, M3, P1, T1 and A1 by polymerase chain reaction (PCR) on leucocyte DNA in patients from North Staffordshire, Birmingham and Liverpool with alcohol-related chronic liver disease heavy drinking and normal local controls. RESULTS: There were no significant differences in GSTM1, GSTM3 or GSTP1 genotype frequencies among patients, drinking and non-drinking controls from the three centres. There was a significant increase in the GSTT1 null Liverpool alcoholic liver disease (ALD) patients compared with corresponding non-drinking controls (26.3 and 14.6%, respectively; P = 0.044, odds ratio (OR) = 2.1, 95% CI = 1.1-4.7) though this was not repeated in the Birmingham and North Staffordshire cohorts. For GSTA1, the -69 CC genotype was associated with increased risk of ALD in the Liverpool group, but a reduced risk in the North Staffordshire group. CONCLUSIONS: We have failed to demonstrate within the limitation of a case-control study a reproducible significant association of GST polymorphisms with susceptibility to ALD but there are suggestions that GSTA1 and GSTT1 warrant further study.     

高砷暴露致皮肤损伤人群尿砷代谢产物分析

目的 探讨高砷暴露致皮肤损伤人群尿砷代谢的特点.方法 应用氢化物发生.冷阱捕获.原子吸收分光光度法测定高砷暴露地Ⅸ(水砷浓度分别为0.21、0.24、0.36 mg/L)皮肤损伤组人群(77人)和未见皮肤损伤对照组人群(77人,性别、年龄1:1配比)尿中无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量.以iAs、MMA及DMA的总和表示总砷(tAs)水平;以iAs/tAs、MMMtAs和DMA/tAs分别计算iAs%、MMA%、DMA%;以(MMA+DMA)/tAs及DMM(MMA+DMA)分别计算一甲基化率(FMR)和二甲基化率(SMR)水平.结果 皮肤损伤组人群与对照组人群相比尿中各形态砷化合物及总砷含量差异无统计学意义(JD>0.05),而皮肤损伤组尿iAs%水平高于对照组,DMA%、FMR和SMR水平低于对照组差异均有统计学意义(P<0.05).皮肤损伤组人群中男性SMR水平显著低于女性,且尿中MMA%显著高于女性(P<0.05).结论 高砷暴露情况下,出现皮肤损伤症状的人群对砷的甲基化能力较低.

Abstract：

Objective To explore the characteristics of urine arsenic metabolism of people with skin lesion. Methods The levels of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) in urine were detected with hydride generation-cold trap-atomic absorption spectroscopy among population exposed to higher levels of arsenide (0.24 ,0.36,0.21 mg/L), which consisted of skin lesion group(n=77) and non-skin lesion group (n=77,control group) in Apr.,2009 . Total arsenic (tAs) , iAs %, MMA%, DMA%, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were calculated as iAs + MMA+ DMA , iAs/tAs, MMA/tAs, DMA/tAs, (MMA + DMA)/ tAs and DMA/(MMA + DMA), respectively. Results No significant difference was observed in urinary concentrations of arsenic species and tAs between two groups (P>0.05), iAs% was much higher and the levels of FMR, SMR and DMA% were significantly lower in skin lesion group compared with the control (P<0.05). There were statistically significant differences in iAs% and SMR between males and females of the skin lesion group(P<0.05). Conclusion The arsenic methylation capacity of the persons with skin lesions is lower at high arsenic exposure.     

Cigarette smoking and colorectal cancer: APC mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms

The contribution of cigarette smoking to sporadic colorectal cancer may differ according to molecular aspects of the tumor or according to glutathione S-transferase M1 (GSTM1) or glutathione S-transferase T1 (GSTT1) genotype. In the prospective Netherlands Cohort Study on Diet and Cancer, adjusted incidence rate ratios for 1986-1993 were computed for overall colorectal cancer, tumors with and without adenomatous polyposis coli (APC) mutations, and tumors with and without human mut-L homologue 1 (hMLH1) expression, according to cigarette smoking characteristics (661 cases, 2,948 subcohort members). Case-only analyses were performed to estimate odds ratios for interaction between cigarette smoking and GSTM1 and GSTT1 genotypes. In comparison with never smokers, a high smoking frequency increased the risk of colorectal cancer (for a five-cigarette/day increment, incidence rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.03, 1.12), and this association was stronger in 371 tumors without a truncating APC mutation (IRR = 1.11, 95% CI: 1.05, 1.17). Long-term smoking was associated with lack of hMLH1 expression in 56 tumors (for a 10-year increment, IRR = 1.17, 95% CI: 1.00, 1.37). No statistically significant interactions between smoking and GSTM1 or GSTT1 genotype were observed. These results indicate that cigarette smoking is associated with risk of colorectal cancer, and this association may depend on molecular characteristics of the tumor as defined by APC mutation and hMLH1 expression status.     

A pathway-based analysis of urinary arsenic metabolites and skin lesions

Inorganic arsenic is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Limited evidence suggests that the ability to fully metabolize arsenic into DMA influences susceptibility to disease. To determine whether percentage of MMA was predictive of disease, the authors used data from a case-control study conducted in Bangladesh (2001-2003). Persons who were diagnosed with keratosis, melanosis, Bowen's disease, or squamous cell carcinoma were matched on age, sex, and village to persons without these conditions. This analysis was restricted to persons who had no missing data on covariates (859 cases, 868 controls). A path analysis was used to evaluate simultaneously the association between the percentage of all urinary arsenic metabolites and the odds of skin lesions using PROC CALIS in SAS, version 9.1 (SAS Institute, Inc., Cary, North Carolina) and Mplus, version 6.1 (Muthén & Muthén, Los Angeles, California). The odds of skin lesions were significantly associated with log(10) percentage of MMA (adjusted odds ratio (OR(adj)) = 1.56, 95% confidence interval (CI): 1.15, 2.12) but not log(10) percentage of inorganic arsenic (OR(adj) = 1.06, 95% CI: 0.75, 1.50) or log(10) percentage of DMA (OR(adj) = 1.07, 95% CI: 0.33, 3.46). This novel analysis confirmed that persons who excrete a higher proportion of MMA have a greater risk of skin lesions after data are adequately controlled for urinary arsenic metabolites, current arsenic exposure, and other risk factors.     

中国汉族人口三种谷胱甘肽S-转移酶基因多态性分析

目的：分析中国汉族人口谷胱甘肽S－转移酶（GSTs)基因多态性分布。方法：样本为450名中国汉族人口,采用多重等位基因特异聚合酶链反应（PCR）方法分析GSTM1和GSTT1基因多态性,采用PCR－限制性片段长度多态性方法分析GSTP1＋313核苷酸位点的基因多态性。结果：GSTM1缺失型和GSTT1缺失型基因型频率分别为57％和45％,同时具有GSTM1缺失型和GSTT1缺失型基因型的人个体频率为28．92％;而GSTP1＋313位点G等位基因频率为18．7％,并发现该人群中同时具有3种危险基因型（GSTM1缺失型、GSTT1缺失型和GSTP1＋313A／A）的个体频率为18．04％。GSTs基因型分布不受性别和年龄的影响。结论：中国汉族人口GSTM1、GSTT1和GSTP1基因呈多态性分布,其等位基因和基因型频率不同于其他种族。     

Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis

OBJECTIVE: In a nested case-control study, the authors investigated whether the deletion polymorphism of glutathione S-transferases GSTM1 and GSTT1 represents a risk factor for the development of asbestosis. METHODS: In total, 262 cases with asbestosis and 265 controls, selected from a cohort of 2080 workers occupationally exposed to asbestos, were genotyped for GSTM1 and GSTT1-null alleles. Cumulative exposure for each subject was available. RESULTS: Asbestosis was associated with cumulative exposure (odds ratio [OR]=3.21, confidence interval [CI] 2.43-4.23) and GSTT1-null genotype (OR=0.61, CI 0.40-0.94), but not with GSTM1-null genotype (OR=1.01, CI 0.71-1.43). The risk of GSTM1-null and GSTT1-null genotype for asbestosis did not change after adjustment by cumulative exposure, smoking, gender, and age. CONCLUSIONS: An important finding of this study is that GSTT1 gene deletion might have a protective effect on the development of asbestosis.     

GSTT1基因、GSTM1基因多态性与乳腺癌易感性的病例-对照研究

目的探讨女性乳腺癌人群中,雌激素代谢酶GSTT1基因、GSTM1基因多态性与乳腺癌易感性的关系。方法采用聚合酶链反应(PCR)对天津市105例正常对照者和100例乳腺癌患者的GSTT1基因、GSTM1基因多态性进行检测,Logistic回归分析评估单个、联合基因以及雌激素暴露相关因素对罹患乳腺癌的危险度。结果GSTT1基因缺失型在两组间分布频率的差别有统计学意义(χ2=13.766,P=0.000),GSTM1基因在两组间分布频率的差别有统计学意义(χ2=13.135,P=0.000);联合基因型分析显示,随着GSTT1或GSTM1基因型缺失情况的出现,个体罹患乳腺癌的危险性增加(趋势性检验,χ2=27.011,P=0.000);GSTM1基因和GSTT1基因同时缺失的人群OR(95%CI)为12.338(3.621～22.042);多因素非条件Logistic回归分析结果显示:GSTT1基因和GSTM1基因缺失与乳腺癌的发生相关。结论雌激素代谢酶相关基因多态性与乳腺癌发生相关。     

三氯乙烯药疹样皮炎代谢酶基因多态性的病例对照研究

目的 筛选三氯乙烯药疹样皮炎的易感基因。方法 比较43例病人和47例健康三氯乙烯接触工人细胞色素P450酶（CYP1A1）、谷胱甘肽S-转移酶（GSTM1、GSTP1、GSTT1）和N-乙酰基转移酶（NAT2）的基因多态性分布，并计算相对危险度，结果 NAT2基因Kpnl位点的变异可显著增加三氯乙烯皮炎的危险性；具有NAT2慢代谢基因型的个体患皮炎危险性显著高于快代谢基因型个体，未发现其它代谢酶基因多态性与三氯乙烯皮炎易感性的相关关系。结论 NAT2基因的变异可能是导致三氯乙烯皮炎个体易感性差异的原因之一。     

谷胱甘肽转硫酶M1和T1基因型与食管癌危险性:病例-对照研究

为探讨参与致癌物代谢的谷胱甘肽转硫酶（ＧＳＴ）Ｍ１和Ｔ１基因多型性与食管癌危险性的关系，以病例－对照分子流行病学方法，分析食管癌高发区河南林县的食管癌、食管上皮重度增生病例和性别、年龄配对的正常对照者（各４５例）的ＧＳＴＭ１和ＧＳＴＴ１基因型分布的差异。基因组ＤＮＡ来自研究对象的食管外科手术标本或细胞学检查获得的食管上皮细胞，以多重聚合酶链反应方法进行基因分型。结果：食管癌、食管上皮重度增生病例和     

Genetic Variation in GSTM1 Is Associated With Susceptibility to Noise-Induced Hearing Loss in a Chinese Population

OBJECTIVES:: To investigate whether glutathione S-transferases (GST) genetic polymorphisms (GSTT1 rs1049055, GSTM1 rs10712361, and GSTP1 rs1695) are associated with susceptibility to noise-induced hearing loss (NIHL). METHODS:: These polymorphisms were analyzed in 444 NIHL and 445 normal hearing workers. In addition, total plasma GST activity was measured in all subjects. RESULTS:: Individuals with the GSTM1 null genotype had a statistically significantly increased risk of NIHL (odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.26 to 2.13) compared with those carrying a wild-type GSTM1 genotype. This effect was more pronounced among the workers exposed to 86 to 91 dB(A) (OR = 3.35, 95% CI = 1.54 to 7.31). Glutathione S-transferase activity of the NIHL workers was also lower than that of normal hearing workers (14.5 ± 5.1 U/ml vs 15.9 ± 6.3 U/ml, P = 0.010). CONCLUSION:: Our results suggest that GSTM1 polymorphism is associated with susceptibility to NIHL.