Glutathione S transferase mu polymorphism and gastric cancer in the Portuguese population

The glutathione S-transferases appear to form part of a protective mechanism against the development of cancer where environmental chemical carcinogens are involved. In humans one member of the mu class gene family (GSTM1) has been shown to be polymorphic and is only expressed in ~50% of individuals. Previous studies have shown a possible link between the null phenotype and susceptibility to cancer but have been equivocal regarding stomach cancer. To evaluate any association in Portuguese gastric cancer individuals with GSTM1 variability, we performed GST M 1 polymorphism by PCR amplification in 148 gastric cancer patients and in 84 healthy control individuals. We found no statistical differences between the gastric cancer and control populations (wild type phenotype: 52%, 48%; null phenotype: 48%, 52%, respectively). A subset analysis into site of tumour also revealed no significant differences between the groups, although we found a slight increase of the wild type phenotype in the samples of the antrum compared with the control population (57% vs 48%, respectively; 2= 1.18; p 0.28) and a slight increase of the null phenotype in the signet ring cells/mucocellular group (2= 1.05; p 0.3). However, in both cases it did not reach statistical significance. A subset analysis of the histological groups following the WHO criteria revealed a statistically significant difference (2= 3.704; p 0.05) between the moderately differentiated gastric adenocarcinoma and the presence of the wild type phenotype. These results do not support the hypothesis that the GSTM1 null phenotype predisposes to gastric cancer in the Portuguese population and the moderately differentiated gastric adenocarcinoma seems to be associated with the presence of the G STM 1 wild type phenotype.     

Glutathione S-transferase M1, T1 and P1 genetic polymorphisms, cigarette smoking and gastric cancer risk

Glutathione S-transferases (GSTs) belong to a superfamily of detoxification enzymes that provide critical defences against a large variety of chemical carcinogens and environmental toxicants. GSTs are present in most epithelial tissues of the human gastrointestinal tract. We investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1 and GSTP1), the interaction with cigarette smoking and susceptibility to gastric cancer. The GSTM1, GSTT1 and GSTP1 polymorphisms were determined using real-time polymerase chain reaction (PCR) and fluorescence resonance energy transfer with Light Cycler Instrument. The study included 70 patients with gastric cancer and 204 controls. Associations between specific genotypes and the development of gastric cancer were examined by use of logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 homozygous null genotype was associated with an increased risk of developing gastric cancer (OR = 1.73; 95% CI = 1.10-3.04). GSTT1 homozygous null genotype and GSTP1 genotypes were not associated with the risk of gastric cancer. Also there was no difference between cases and controls in the frequency of val-105 and ile-105 alleles (p = 0.07). After grouping according to smoking status, GSTM1 null genotype was associated with an increased gastric cancer risk for smokers (OR = 2.15; 95% CI, 1.02-4.52). There were no significant differences in the distributions of any of the other GST gene combinations. Our findings suggest that the GSTM1 null genotype may be associated with an increased susceptibility to gastric cancer.     

The association between GSTM1 polymorphism and gastric cancer risk: a meta-analysis

Relationship of gastric cancer with the GSTM1 polymorphism was reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between GSTM1 polymorphism and gastric cancer susceptibility. Relevant studies were identified from PubMed and references of retrieved articles. A meta-analysis was performed, which included 38 studies with 6,605 gastric cancer cases and 11,311 controls. The combined result based on all studies showed there was a significant link between GSTM1 null genotype and gastric cancer (OR = 1.20, 95%CI: 1.08–1.34). When stratifying for the race, the phenomenon was found that gastric cancer case had a significantly higher frequency of GSTM1 null genotype than control in Asians (OR = 1.27, 95%CI: 1.10–1.47). However, there was not enough evidence to show there was a significant difference in GSTM1 null genotype distribution between gastric cancer case and control in Caucasians (OR = 1.13, 95%CI: 0.96–1.32). This meta-analysis indicated that GSTM1 null genotype might be associated with increased gastric cancer risk in Asians. However, this meta-analysis did not provide an evidence of confirming association between GSTM1 polymorphism and gastric cancer in Caucasians.     

The GSTM1 Null Genotype Increased Risk of Gastric Cancer: A Meta-Analysis Based on 46 Studies

Background

Glutathione S-transferases M1 (GSTM1) is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk.

Methods

This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren’s classification, and other factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength.

Results

A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, P_{heterogeneity}<0.001). Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, P_{heterogeneity} = 0.002), but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, P_{heterogeneity}=0.065), while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, P_{heterogeneity}=0.168). For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren’s classification did not modify the association.

Conclusions

In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.     

Investigation of glutathione S-transferase M1 and T1 deletions in lung cancer

Glutathione S-transferases (GSTs) M1 and T1 are known to be polymorphic in humans. Both polymorphisms are due to gene deletions which are responsible for the existence of null genotypes. Previous studies have suggested that GST genotypes may play a role in determining susceptibility to a number of unrelated cancers, including lung cancer. The GSTM1 and GSTT1 polymorphisms were determined by PCR-based analysis in 75 lung cancer patients and 55 controls. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. The frequencies of GSTM1 and GSTT1 null genotypes were 37.3 and 22.7% in lung cancer patients and 27.3 and 16.4% in controls, respectively. When analyzed by histology the GSTM1 null genotype was more prevalent in squamous-cell carcinoma and adenocarcinoma patients. Whereas, GSTT1 null genotype frequency was lower in small-cell lung cancer patients than controls. But these differences were not statistically significant. According to smoking status, null genotype for both gene are associated with an increase in risk for lung cancer. Our results suggest that GSTM1 and GSTT1 polymorphisms may play a role in the development of lung cancer for some histological subtypes and modifies the risk of smoking-related lung cancer.     

Glutathione S-transferase M1, T1, and P1 genotypes and breast cancer risk: a study in a Portuguese population

Glutathione S-transferases are a superfamily of multifunctional enzymes that play a key role in Phase II metabolism, detoxifying therapeutic drugs, and various carcinogens by conjugation with glutathione. We undertook a case-control study in Central-Eastern Portuguese population to evaluate the association of null genotype in GSTM1 and GSTT1 along with the polymorphism in GSTP1 (A/G) and susceptibility to breast cancer. The population sample consisted of 85 patients with histological diagnosis of breast cancer and 102 healthy women. Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR-based methods. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. We found a increased breast cancer risk associated with GSTM1 null genotype (OR = 3.597; 95% CI = 1.849-6.999; P = 0.0001) and GSTT1 (OR = 2.592; 95% CI = 1.432-4.690; P = 0.002), but the presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The two-way combination of GSTM1 and GTTT1 null genotypes resulted in 8-fold increase for breast cancer risk (OR = 8.287; 95% CI = 3.124-21.980; P = 0.0001) and the three-way combination of GSTP1 105AA/AG and null genotypes for both GSTM1 and GSTT1 resulted in 5-fold increase for breast cancer risk (OR = 5.040; 95% CI = 1.392-18.248; P = 0.016). Our results suggest that GSTM1 and GSTT1 null genotype alone, both combined or combined with GSTP1 valine alleles, are associated with higher susceptibility to breast cancer development.     

Relation of glutathione S-transferase T1, M1 and P1 genotypes and breast cancer risk

The aim of this study was to investigate associations between genetic variability in specific Glutathione S-transferases (GST) genes (GSTM1, GSTT1 and GSTP1) and susceptibility to breast cancer. Genotypes of blood specimen DNA were determined for 65 women with incident cases of breast cancer and 108 control subjects. Associations between specific genotypes and the development of breast cancer were examined by the use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Neither GSTT1 nor GSTM1 homozygous null genotype was associated with a significant increased risk of developing breast cancer. The presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The risk of breast cancer associated with a combined GSTT1 and GSTM1 null genotype was 3.37 (95% CI = 0.76-2.95, p = 0.115). The only significant association between increased risk of breast cancer development and GSTs polymorphisms was found when GSTT1 null, GSTM1 null and the presence of valine in GSTP1 in codon 105 were combined (p < 0.048, OR = 3.75, 95% CI = 1.01-13.90). Our findings suggest that combined genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.     

Glutathione-S-transferase M1 and T1 genes and gastric cancer: a case control study in North Indian population

Background

Difference in the capacity of xenobiotic metabolising enzymes might be an important factor in genetic susceptibility to cancer.

Methods

A case control study involving forty one gastric cancer patients and one hundred and thirty controls was carried out to determine the frequency of GSTM1 and GSTT1 null genotypes. The frequency of GSTM1 and GSTT1 null genotype was observed by carrying out multiplex PCR.

Results

There was no difference in the frequencies of the GSTM1 and GSTT1 null and the combined GSTM1 and GSTT1 null genotype between patients and control.

Conclusions

Our data suggest that GSTM1 and GSTT1 status may not influence the risk of developing gastric cancer.     

Interaction between smoking, GSTM1 deletion and colorectal cancer: results from the GSEC study.

Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-mu (GST-mu). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-mu enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (chi2=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype     

Influence of p53 expression on sensitivity of cancer cells to bleomycin

In this study, we determined whether p53 expression affected the sensitivity of non–small cell lung cancer (NSCLC) and colon cancer cells to bleomycin (BLM). Two human NSCLC cell lines (A549 expressing wild‐type p53 and p53‐null H1299) and two colon cancer cell lines (HCT116 p53+/+ and its p53 deficient subline HCT116 p53?/?) were subjected to treatment with BLM. Cells were treated with various concentrations of BLM, and cellular viability was assessed by formazan assay. To investigate the role of p53 in BLM sensitivity, we transduced cells with adenovirus with wild‐type p53, dominant‐negative p53, and GFP control, and analyzed the effect on cellular viability. Cells expressing wild‐type p53 were more sensitive to BLM than p53‐null cells in both NSCLC and colon cancer cells. Sensitivity to BLM of the cells with wild‐type p53 was reduced by overexpression of dominant‐negative p53, while BLM sensitivity of p53‐null cells was increased by wild‐type p53 in both NSCLC cells and colon cancer cells. In conclusion, our data show that p53 sensitizes all four cancer cells lines tested to BLM toxicity and overexpression of p53 confers sensitivity to the cytotoxic activity of the anticancer agent in p53‐null cells. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:260–269, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20334     

GST genotypes and lung cancer susceptibility in Asian populations with indoor air pollution exposures: a meta-analysis

About half of the world's population is exposed to smoke from heating or cooking with coal, wood, or biomass. These exposures, and fumes from cooking oil use, have been associated with increased lung cancer risk. Glutathione S-transferases play an important role in the detoxification of a wide range of human carcinogens in these exposures. Functional polymorphisms have been identified in the GSTM1, GSTT1, and GSTP1 genes, which may alter the risk of lung cancer among individuals exposed to coal, wood, and biomass smoke, and cooking oil fumes. We performed a meta-analysis of 6 published studies (912 cases; 1063 controls) from regions in Asia where indoor air pollution makes a substantial contribution to lung cancer risk, and evaluated the association between the GSTM1 null, GSTT1 null, and GSTP1 105Val polymorphisms and lung cancer risk. Using a random effects model, we found that carriers of the GSTM1 null genotype had a borderline significant increased lung cancer risk (odds ratio (OR), 1.31; 95% confidence interval (CI), 0.95-1.79; p=0.10), which was particularly evident in the summary risk estimate for the four studies carried out in regions of Asia that use coal for heating and cooking (OR, 1.64; 95% CI, 1.25-2.14; p=0.0003). The GSTT1 null genotype was also associated with an increased lung cancer risk (OR, 1.49; 95% CI, 1.17-1.89; p=0.001), but no association was observed for the GSTP1 105Val allele. Previous meta- and pooled-analyses suggest at most a small association between the GSTM1 null genotype and lung cancer risk in populations where the vast majority of lung cancer is attributed to tobacco, and where indoor air pollution from domestic heating and cooking is much less than in developing Asian countries. Our results suggest that the GSTM1 null genotype may be associated with a more substantial risk of lung cancer in populations with coal exposure.     

Polymorphisms of DNA repair and xenobiotic genes predispose to CpG island methylation in non-neoplastic gastric mucosa

Background: Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non‐neoplastic gastric mucosa. Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP‐kinase and CDH1) loci, assessed by Methylation‐Specific‐Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated. Results: Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP‐kinase (adjusted OR = 0.30, 95%CI = 0.13–0.71, p = .0055) and CIHM high (OR = 0.42, 95%CI = 0.19–0.97, p = .04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes (p = .02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50 years and older generations (OR = 1.63, 95%CI = 1.01–2.62, p = .045). Conclusion: XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP‐kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM‐related gastric carcinogenesis.     

Assessment of the association between GSTM1 null genotype and risk of type 2 diabetes

Many studies have investigated the association between Glutathione S-Transferase M1 (GSTM1) null genotype and risk of diabetes mellitus, but the impact of GSTM1 null genotype on diabetes mellitus is unclear owing to the obvious inconsistence among those studies. This study aimed to quantify the strength of association between GSTM1 null genotype and risk of diabetes mellitus. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTM1 null genotype and risk of diabetes mellitus. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by type of diabetes and ethnicity. 10 case–control studies with 7, 054 subjects were included into this meta-analysis. Meta-analysis of total 10 studies showed GSTM1 null genotype was associated increased risk of diabetes mellitus (OR = 1.59, 95 % CI 1.14–2.22, P = 0.007). Subgroup analyses by type of diabetes mellitus suggested GSTM1 null genotype was associated increased risk of type 2 diabetes (OR = 1.90, 95 % CI 1.37–2.64, P < 0.001), but was not associated with risk of type 1 diabetes (OR = 0.84, 95 % CI 0.66–1.07, P = 0.153). Subgroup analysis by ethnicity further identified the obvious association between GSTM1 null genotype and increased risk of type 2 diabetes. The cumulative meta-analyses showed a trend of obvious association between GSTM1 null genotype and risk of type 2 diabetes as information accumulated. No evidence of publication bias was observed. Thus, evidence from current meta-analysis suggests an association between GSTM1 null genotype and risk of type 2 diabetes.     

Polymorphisms in detoxification genes CYP1A1, CYP2E1, GSTT1 and GSTM1 in gastric cancer susceptibility

Cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes are involved in activation and detoxification of many potential carcinogens. Genetic polymorphisms in those enzymes have been found to influence the interindividual susceptibility to cancer. Some polymorphisms of those enzymes have been associated specifically with susceptibility to gastric cancer. We conducted a study in a Costa Rican population, where gastric cancer incidence and mortality rates are among the highest in the world. We investigated whether such variations affected the risk of developing gastric cancer. Subjects included 31 with gastric cancer, 58 controls with gastric injures others than cancer and 51 normal controls confirmed by X-rays (double-contrast) or endoscopic diagnostic. DNA from peripheral white blood cell was obtained from all subjects. Deletion of GSTT1 and GSTM1 was assessed by multiplex PCR and genotyping of CYP2E1 was performed using a PCR-based restriction fragment length polymorphism assay with the restriction enzyme PstI and the gene CYP1A1 using the restriction enzyme MspI The prevalence of CYP1A1 Msp1 polymorphism, GSTT1 and GSTM1 null genotype was similar in the three groups of individuals (p = 0.73, p = 0.88 y p = 0.89 respectively). Our findings suggest that the polymorphism CYP2E1 PstI could be associated with a reduced risk of having gastric cancer (OR = 0.09, IC95%:0.01 - 0.83).     

Polymorphisms of cytochrome P450 1A1, glutathione s-transferases M1 and T1 genes in Ouangolodougou (Northern Ivory Coast)

In this study, the frequencies of CYP1A1, GSTM1, and GSTT1 gene polymorphisms were determined in 133 healthy individuals from Ouangolodougou, a small rural town situated in the north of the Ivory Coast. As appeared in several published studies, ethnic differences in these frequencies have been found to play an important role in the metabolism of a relevant number of human carcinogens. In the studied sample, the frequencies of Ile/Ile (wild type), Ile/Val (heterozygous variant), and Val/Val (homozygous variant) CYP1A1 genotypes were 0.271, 0.692, and 0.037, respectively. Frequencies of GSTM1 and GSTT1 null genotypes were 0.361 and 0.331, respectively. No significant differences were noted between men and women. In contrast to published data for Africans, CYP1A1 *Val Allele frequency (0.383) was significantly high (p < 0.001) in this specific population. For the GSTT1 null genotype, no differences were found between the studied and other African populations, the contrary to what occurred for the GSTM1 null genotype in relation to Gambia and Egypt.     

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.     

The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population

The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM.     

Polymorphisms of the GSTM1 and CYP2D6 genes associated with susceptibility to lung cancer in Chinese.

The case-control study was conducted to examine the association between GSTM1 null and CYP2D6Ch (T(188)/T) genotypes and lung cancer risk among Chinese of Han nationality living in Guangdong. All 191 subjects were investigated with unitary questionnaire and their DNAs were isolated from peripheral lymphocytes by standard procedures with proteinase K digestion and phenol/chloroform extraction. GSTM1(-) was detected with polymerase chain reaction (PCR) in all 191 subjects, involving 59 lung cancer cases, 59 hospital controls and 73 healthy controls. The frequencies of GSTM1(-) were not significantly different between the cases and the two controls overall. However, among adenocarcinoma of lung, the frequency of GSTM1(-) (76.9%) appeared to be higher than that in controls (49.2%), and the odd radios were 3.42-3.45. The results suggested an elevated risk for adenocarcinoma of lung would be shown by GSTM1(-). Using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) to detect CYP2D6 T(188)/T genotype in 59 lung cancer patients and 59 hospital controls, it showed no significant difference between the two groups. However, non-smokers with non-T(188)/T (C(188)/C or C(188)/T) genotype showed 3.78-folds increased risk of lung cancer compared with those with T(188)/T genotype (P=0.036). The data did not suggest a substantial interaction effect between GSTM1 and CYP2D6 polymorphisms and the risk of lung cancer. Additionally, among Chinese (Han) of Guangdong, the frequency of CYP2D6 T(188) allele appeared to be 57.2%, and GSTM1(-) to be 51.8%.