GSTM1 Null Type Research Articles

Phenotypic expression and polymorphism of Glutathione S Transferase gene in materno-fetal dyads with idiopathic fetal growth restriction

IntroductionIncidence of fetal growth restriction (FGR) in India is quite high, and FGR has been found to be associated with various non-infectious diseases including coronary artery disease, diabetes mellitus and metabolic syndrome. Moreover, 40% of FGR is termed idiopathic (IFGR) for which cause is not known. Oxidative stress, which is postulated to have a role in FGR, is modulated by polymorphism of antioxidant genes. This study aims to examine association of GST polymorphism and enzymatic activity with incidence of FGR. Materials and methods150 unrelated live births participated as dyads (mother and neonate). 75 consecutive IFGR materno-fetal dyads (referred subsequently as IFGR mother and IFGR neonate) were recruited as cases. Polymorphic analysis of GSTT1 and GSTM1 were carried out by multiplex PCR. Glutathione-S-transferase activity in serum was measured using 1-chloro-2, 4-dinitrobenzene (CDNB) as substrate. ResultsIncidence of GSTT1 null type is significantly higher in IFGR fetus and their mothers (p < 0.01). Incidence of GSTM1 null type is significantly higher in IFGR fetus (p = 0.001). GST activity levels in mothers giving birth to IFGR babies was about 50% of the values found in the control group (p < 0.001). The GST activity levels in control group was found to be 50% higher than the FGR babies (p = 0.001). ConclusionOur results show that there is definite association between polymorphism of GST genes and incidence of IFGR. Simultaneously, our study also found a correlation between maternal GST activity and fetal weight.

Purple grape juice supplementation in smokers and antioxidant status according to different types of GST polymorphisms.

DNA damages and antioxidant status was assessed after 8 weeks of purple grape juice supplementation in male smokers depending on the glutathione S-transferase polymorphisms. Ninety-five smokers consumed 480 ml of purple grape juice for 8 weeks. The blood samples were collected before and after supplementation to measure lymphocyte DNA damages, plasma antioxidants, conjugated diene, and the erythrocyte antioxidant enzymes. The diastolic pressure, lymphocyte DNA damage, and plasma conjugated diene were significantly decreased but the plasma γ-tocopherol was increased in GSTM1-null genotype, while increased blood glutathione and decreased lymphocyte DNA damage were observed in GSTM1-present genotype. In case of GSTT1 on the other hand, the decrease in diastolic pressure and lymphocyte DNA damage was observed in both null types and present types, but the erythrocyte catalase activity was decreased in GSTT1-null type and the plasma vitamin C level was increased in GSTT1-present type, suggesting that, the antioxidant effect of grape juice was greater in GSTT1-present type compared to GSTT1-null type. The intakes of 8-week purple grape juice affected diastolic blood pressures, DNA damage reductions and antioxidant status in smokers, mainly greater in GSTM1-null type and GSTT1-present type.

Association of GSTM1 and GSTT1 gene polymorphisms and in-vitro fertilisation outcome in a population in northern Iran

Implantation failure is a major limiting step for in-vitro fertilisation (IVF). Embryo implantation is the result of the interaction of the embryo with the endometrium. Oxidative stress (OS) can cause defective embryo development and retardation. Genetic polymorphisms of detoxicating enzymes, such as glutathione S-transferases (GSTs), may play an important role in the outcome of embryo implantation. GSTM1 and GSTT1 are known to be highly polymorphic. The aim of this study was to examine the association of GSTM1 and GSTT1 gene polymorphisms with IVF-ET outcome in a population in northern Iran. Blood samples were collected from 120 infertile women who underwent an IVF cycle, and 108 healthy volunteers. Genomic DNA was prepared from peripheral blood leucocytes. Genotype frequencies were determined in patients and healthy controls using polymerase chain reaction (PCR). It was found that 25.8% of the infertile women and 0% of the controls had the GSTM1 null genotype (odds ratio (OR) = 76.37; 95% CI = 4.6–1,265.7; p = 0.0025). On the other hand, 5% of the cases and 0% of the controls had the GSTT1 null genotype (OR = 12.3, 95% CI = 0.68–221/3, p = 0.088). These results suggest that GSTM1 null type might be associated with IVF outcome in a population in northern Iran.

Role of glutathione S transferase polymorphism in COPD with special reference to peoples living in the vicinity of the open cast coal mine of Assam.

BackgroundCOPD may develop due to variation in the functioning of antioxidants along with smoking and environmental factors in genetically susceptible individuals. Since there are different views about the antioxidants responsible for detoxifying xenobiotic compound in the human body whose functional variation may lead to obstructive disease, this associative study has been taken up between GST gene polymorphism and COPD in populations exposed to coal dusts.MethodsGenotypes of the 70 COPD patients and 85 non COPD patients were determined by PCR based methods followed by multiplex PCR of GSTT1 and GSTM1 genes taking albumin gene as a control. Suspended particulate analyses were determined through the Respirable Dust sampler along with the FTIR analysis of the dust samples from the glass microfiber filters.ResultsDust sampling analysis reveals higher level of respirable suspended particulate matter, non respirable particulate matter, SO2 and NO2 present in air of the study site. FTIR analysis also suggests a higher concentration of organic silicone and aliphatic C-F compounds present in air of the study site and when spirometry was done, low lung function was observed among most of the subjects. GSTM1 null type was significantly associated with low lung function in smoker groups and the presence of at least one active allele (either GSTM1/GSTT1) seemed to have a protective role in the development of COPD.ConclusionsGSTM1 (null genotype) appeared to be a risk factor for lower lung function in smokers living in the vicinity of coal mines. Apart from polluted environment and genetic susceptibility, mixed coal dust exposure rich in organic silicone and aliphatic C-F compounds also appears to be a factor for the low lung function.

Gene-Smoking Interaction on Ischemic Stroke: Case-Control Study of Glutathione S-Transferase Polymorphism

Background: Smoking is a major risk factor of stroke, but not all smokers develop stroke. This individual difference could be explained by the variation of detoxification capacity. We investigated the relationship of smoking with the genetic polymor - phism of a detoxification enzyme (glutathione S-transferase: GST). Methods: This study was conducted as a case-control study. Conventional risk factors for stroke and 3 genetic polymorphisms of GST (GSTM1, GSTT1, and GSTP1) were studied in both 290 acute ischemic stroke patients and 290 age and sex matched controls. Smoking status was determined by urinary cotinine level. The effect of interaction of GST polymorphisms and smoking on stroke risk was investigated. Results: Stroke patients had higher cotinine level compared to that of control (P<0.01). There was little difference between the patient group and control group with regard to the GST polymorphism alone, but significant interaction was noticed between the GST polymorphism and the smoking status. When we stratified the group according to the smoking status by cotinine level, stroke was significantly more frequent in GSTM1 null type and GSTT1, GSTP1 wild type of the high cotinine level group (OR and 95% CI: 2.115, 1.219-3.670; 2.620, 1.480-4.638; 2.212, 1.343-3.644 respectively). Conclusion: GST polymorphisms interact with the smoking and confer an increased risk of ischemic stroke, indicating that genetic polymorphism of GST might reveal smokers who are more susceptible to the ischemic stroke. (Korean J Stroke 2012;14:67-73)

Polymorphisms of Dioxin Receptor Complex Components and Detoxification-Related Genes Jointly Confer Susceptibility to Advanced-Stage Endometriosis in the Taiwanese Han Population

To establish a multilocus model for studying the effect of dioxin receptor complex components and detoxification-related enzymes on advanced endometriosis. Six single-nucleotide polymorphisms (SNPs) and two deletion polymorphisms from eight genes (CYP1A1, CYP1B1, GSTM1, GSTT1, GSTP1, AhR, ARNT, and AhRR) were genotyped. In the single SNP analysis, GSTM1 null type and AhRR variant type were associated with a significantly increased risk of endometriosis [odds ratio (OR)=2.38 and 2.45, respectively]. Using multiple SNPs in the logistic regression for covariates, wild-type AhR and mutant AhRR combination was significantly higher in patients (67.8%) than in controls (48.0%) (OR=2.76). On the other hand, mutant AhRR in combination with GSTM1 null genotype was significantly higher in patients (35.5%) than in controls (19.3%) (OR=6.12). Polymorphisms of dioxin receptor complex components and detoxification-related genes jointly confer susceptibility to advanced-stage endometriosis in the Taiwanese Han population.

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran

We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47-5.64; P=0.005, and OR=3.21, 95% CI: 2.52-5.64; P=0.005, respectively) (Pcorrected=0.0062). The frequency of GSTP1 Val/Val genotype was 14.3% in cases compared with 2.4% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (OR=3.72, 95% CI: 1.67-5.65; P=0.002). The risk associated with the concurrent absence of both of the genes (OR=4.8, 95% CI: 2.34-6.78) was greater than the product of risk in men with either null (OR=1.52, 95% CI: 0.82-2.31) genotype combinations (P=0.001, Pcorrected=0.0045). The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83-16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64-7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31-5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.

The influence of Glutathione‐S‐transferase(GSTs) polymorphisms on the level of oxidative DNA damage, antioxidant status and lipid profiles in healthy Korean adults

Human glutathione‐S‐transferases (GSTs) are known as phase □ enzymes involved in the detoxification to protect oxidative stress. This study compares the contribution of GSTT and GSTM genetic polymorphism on the susceptibility to oxidative damage or to antioxidant status on healthy subjects depending on their smoking status. The degree of DNA damage in smokers (n=48) were not significantly different than that of non‐smokers(n=197). Similarly, the levels of total radical trapping antioxidative potential(TRAP), erythrocyte SOD, GST‐Px and catalase showed slight increase in the GSTT1, GSTM1 null type, but, was not significantly different. Plasma HDL‐Chol was significantly higher in the GSTM1 null type(p&lt;0.05), while the other parameters were not different. In non‐smokers, GSTT1 null genotype had significantly higher DNA damage than the wild type(p&lt;0.05). Plasma TRAP and the levels of antioxidant enzymes did not show any significant difference depending on the genotype. When all these effect was adjusted with smoking status, GSTM1 wildtypes and GSTT1 null types showed lower overall oxidative stress. (This study was supported grant, 2009‐0069893, from the National Research Foundation of Korea)

Glutathione S-Transferase M1 and T1 Polymorphisms and Susceptibility to Oxidative Damage in Healthy Korean Smokers

Aims: The relationship between glutathione S-transferase (GST) polymorphisms and susceptibility to smoking-induced oxidative damage was investigated in healthy Korean smokers. Methods: Forty-nine healthy male smokers (20–59 years) participated in the study. GSTT1 and GSTM1 genotypes were determined, and lymphocyte DNA damage was assessed by the Comet assay. Results: Out of the 49 smokers, 20 individuals were GSTT1 positive and 29 were GSTT1 null. For GSTM1, 45 smokers were GSTM1 positive and 4 were GSTM1 null. HDL cholesterol levels (p = 0.011) and the atherogenic index of plasma (p = 0.01) were significantly reduced, and concentrations of conjugated dienes were increased (p = 0.01) in the GSTT1-null individuals but not in the GSTT1-positive individuals. The GSTT1-null individuals were more susceptible to DNA damage than the GSTT1-positive individuals. For all parameters, the GSTM1 genotypes were excluded from statistical analyses due to the small number of subjects with the GSTM1-null type. Conclusions: Our findings suggest that subjects with the GSTT1-null genotype were more susceptible to oxidative damage than the GSTT1-positive subjects. Therefore, the GSTT1-null genotype may confer an increased risk of smoking-related cardiovascular disease.

Oxidative stress-related gene interactions with preterm delivery in Korean women

We hypothesized that the cytochrome P450IA1 (CYP1A1), glutathione S-transferases mu 1 (GSTM1), and theta 1 (GSTT1) polymorphisms are associated with the risk for preterm delivery. This study was undertaken to identify gene-gene interactions and haplotypes that increase the risk of preterm delivery. This case-control study was performed in Korea on 145 women with preterm birth and 120 normal controls. Logistic regression and multifactor dimensionality reduction analysis were used to explore single genes and gene-gene interactions, which have an impact on the risk of preterm delivery, respectively. The GSTM1 null genotype and the interaction between the CYP1A1-I462V and GSTM1 null type conferred a risk of preterm birth. The association between preterm delivery and the CYP1A1-T6235C/I462V haplotype plus GSTM1 null type was verified. The interaction between the CYP1A1-I462V and GSTM1 null genotype were found to increase the risk for preterm birth in Korean women. This finding provides evidence of a gene-gene interaction, which has an impact on preterm delivery.

Glutathione S-transferase polymorphism of neonatal hyperbilirubinemia in Korean neonates

Purpose : Glutathione S-transferase (GST) is a polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous diseases. Several allelic variants of GSTs show impaired enzyme activity and are suspected to increase the susceptibility to diseases. Bilirubin is bound efficiently by GST members. The most commonly expressed gene in the liver is GSTM1, and GSTT1 is expressed predominantly in the liver and kidneys. To ascertain the relationship between GST and neonatal hyperbilirubinemia, the distribution of the polymorphisms of GSTT1 and GSTM1 were investigated in this study. Methods : Genomic DNA was isolated from 88 patients and 186 healthy controls. The genotypes were analyzed by polymerase chain reaction (PCR). Results : The overall frequency of the GSTM1 null was lower in patients compared to controls (P=0.0187, Odds ratio (OR) =0.52, 95% confidence interval (CI), 0.31-0.88). Also, the GSTT1 null was lower in patients compared to controls (P=0.0014, OR=0.41, 95% CI=0.24-0.70). Moreover, the frequency of the null type of both, in the combination of GSTM1 and GSTT1, was significantly reduced in jaundiced patients (P=0.0008, OR=0.31, 95% CI=0.17-0.61). Conclusion : We hypothesized that GSTM1 and GSTT1 might be associated with neonatal hyperbilirubinemia. However, the GSTT1 and GSTM1 null type was reduced in patients. Therefore the null GSTT1, null GSTM1, and null type of both in the combination of GSTM1 and GSTT1 may be not a risk factor of neonatal jaundice.

Association of glutathione S-transferase gene polymorphisms ( GSTM1 and GSTT1) of vitiligo in Korean population

Vitiligo is an acquired pigmentary disorder of the skin involving melanocyte dysfunction. It has been reported that melanocyte impairment could be related to increased oxidative stress. The glutathione S-transferases ( GSTs) are group of polymorphic enzymes that are important in protection against oxidative stress. To find the relationship between GSTM1 and GSTT1 polymorphisms with vitiligo susceptibility, GSTM1 and GSTT1 (homozygous deletion vs. non-deleted) polymorphisms between vitiligo patients ( n = 310) and healthy controls ( n = 549) were analyzed. We observed significant association in null alleles of the GSTM1 ( P < 0.001, OR = 2.048, 95% CI = 1.529–2.743). GSTM1 null type was also statistically different between two vitiligo subtypes and controls (Focal P < 0.001, OR = 2.224, 95% CI = 1.499–3.298; Generalized P = 0.001, OR = 1.974, 95% CI = 1.342–2.904). However, no significant association in GSTT1 ( P = 0.869, OR = 1.024, 95% CI = 0.775–1.353) was observed with vitiligo. In combined analysis of GSTM1 and GSTT1, both null type and GSTM1/ GSTT1 (null/present) group showed significant differences between controls and vitiligo patients. These results suggest that GSTM1 null type might be associated with vitiligo susceptibility in Korean population.

Phase I/II enzyme gene polymorphisms and esophageal cancer risk: A meta-analysis of the literature

Phase I/II enzymes metabolize environmental carcin-ogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations. Eligible studies were case-control or cohort studies published until September 2004 that were written in any language. From PubMed and a manual review of reference lists in relevant review articles, we obtained 16 studies related to the CYP1A1 Ile-Val substitution in exon 7, CYP1A1 MspI polymorphisms, CYP2E1 RsaI polymorphisms, GSTM1 null type, GSTT1 null type and GSTP1 Ile104Val. All were of case-control design. Summary statistics were odds ratios (ORs) comparing heterozygous-, homozygous-non-wild type or these two in combination with the homozygous wild type, or the null type with the non-null type for GSTM1 and GSTT1. A random effect model was used to estimate the summary ORs. A meta-regression analysis was applied to explore sources of heterogeneity. Individuals with the Ile-Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs (95%CI) compared with Ile/Ile of 1.37 (1.09-1.71), 2.52 (1.62-3.91) and 1.44 (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant association was found between esophageal cancer risk and the other genetic parameters. A significant association exists between the CYP1A1 Ile-Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the internal exposure to activated carcinogens may increase the risk of esophageal cancer.

THE INTERACTIVE EFFECT OF AIR POLLUTION AND GST POLYMORPHISMS ON BIRTH OUTCOMES

ISEE-100 Abstract: Prenatal air pollution exposure has been associated with adverse pregnancy outcome such as low birth weight and preterm birth. Glutathione-S-transferase (GST) is one of the multigene family of phase II metabolic enzyme that detoxify the exogenous chemicals. This study was designed to evaluate the association between prenatal exposure to air pollutants and adverse birth outcome, and the interaction with the GST polymorphisms. We investigated 237 pregnant women who visited a university hospital in Seoul, South Korea. We obtained their address and personal data by questionnaire. The last menstrual period and ultrasound assessment were used to estimate gestational age. Each woman was estimated for air pollution exposure considering the individual address and the monitoring site. For each trimester, we estimated the means of concentration of air pollutants such as aerodynamic diameter less than 10 mm (PM10), nitrogen dioxide (NO2) and carbon monoxide (CO). GSTT1 and GSTM1 genotypes were determined for each pregnant woman. Classified by the GSTT1 and GSTM1 polymorphisms, we analyzed the relationship between birth outcomes and air pollutants (lower than median concentration vs. above), controlling for maternal age and gestational age. We found that neonatal birth weight decreased as air pollutant levels increased in the women with GSTT1 null type. We observed similar results for birth length and gestational age. For the women with GSTM1 null type, higher CO exposure was associated with reduced gestational age (p=0.022).

Decreased lung function associated with occupational exposure to epichlorohydrin and the modification effects of glutathione s-transferase polymorphisms.

Epichlorohydrin (1-chloro-2,3,-epoxypropane; ECH) is a strong irritant of the eyes, respiratory tract, and skin. Because the toxic effect of various chemicals can be modified by metabolic traits, in this study, we also investigated the influence of the glutathione S-transferase (GSTM1) and (GSTT1) genes on the toxic effect of ECH. In the GSTM1 null genotype workers, there is a dose-response of lung function tests (FEV1, FEV1/FVC, MMEF) for ECH exposure, but not in the GSTM1 non-null genotype workers. The ECH exposure was found to be significantly associated with a decreased FEV1 value (P = 0.09) and a decreased MMEF value (P = 0.053) after adjusting for other factors. The GSTM1 null genotype was found to be significantly associated with a decreased FEV1 value (P = 0.038), decreased FEV1/FVC value (P = 0.056), and decreased MMEF value (P = 0.012) after adjusting for other factors. This study indicates that obstructive lung abnormalities and small airway lung damage are associated with ECH exposure, and ECH workers with GSTM1 null-type are also associated with increased respiratory damage.

Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations.

This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p<.001) and in smokers (p<.01), and with the 2-naphthol level in non-smokers (p<.01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

Genetic polymorphisms in cytochrome P450 (CYP) 1A1, CYP1A2, CYP2E1, glutathione S-transferase (GST) M1 and GSTT1 and susceptibility to prostate cancer in the Japanese population

Associations between genetic polymorphisms of CYP1A1, CYP1A2, CYP2E1, GSTM1 and GSTT1 and prostate cancer (PCa) were analyzed in a case-control study of 315 individuals. The frequency of valine (Val)/valine (Val) genotypes for CYP1A1 was 11.3% in cases compared with 5.5% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (odds ratio=2.4, 95% confidence interval (CI)=1.01–5.57). No links were detected between PCa and polymorphisms in other enzymes. However, the combination of CYP1A1 (Ile/Val and/or Val/Val) polymorphisms with the GSTM1 null type resulted in an OR of 2.2 (CI=1.10–4.57, 1.12–4.20, respectively). This study suggests that the CYP1A1 polymorphism and its combination with GSTM1 may be associated with PCa susceptibility in the Japanese population.

Association of genetic polymorphism of glutathione S-transferase M1, T1 and N-acetyltransferase 1 with lung cancer

Background : Smoking and high-risk occupation have been known to be the risk factors of lung cancer. The carcinogen-metabolizing enzymes in human body such as glutathione S-transferase M1, T1 and N-acetyltransferase 1 have also been regarded as risk factors in many cancers, because the activities of those enzymes play a role in metabolizing the carcinogen. A case-control study was conducted to evaluate the genetic polymorphism of GSTM1, T1 and NAT1 in lung carcinogenesis in Korean men. Methods : The histologically proven lung cancer cases were recruited from Seoul National University Hospital. The patients of more than 40-year-old with the nonmalignant urinary tract diseases were recruited as controls from the same hospitals. The informations of demographical characteristics and smoking were obtained by interview or chart review and the genetic polymorphisms of GSTM1, T1 and NAT1 were determined by PCR-based assay. The statistical analyses were performed by linear logistic regression. Results : The number of case-control was 118 and 150, respectively. The smoking history was significantly higher in the lung cancer patients than the controls. The prevalence of GSTM1 null-type was statistically higher(OR=2.25 ; 95% CI=1.12-4.51) in squamous cell carcinoma than other genotypes, but other histologic types were not The prevalence of GSTT1 null-type were not statistically higher than other genotypes in all histologic types. The fast acetylator of NAT1 was more prevalent than normal(OR=2.13 ; 95% CI=1.04-4.40) in all lung cancer patients. Conclusion : The null-type of GSTM1 and fast acetylator of NAT1 are associated with development of lung cancer in Korean men.