Glulathione-S-transferases Gene Polymorphism in Prediction of Gastric Cancer Risk by Smoking and Helicobacter Pylori Infection Status

Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastriccancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched casecontrolstudy with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 andGSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantlyassociated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95%CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was foundfor GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes withthe risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk ofgastric cancer, and smoking modifies the association.     

GSTM1 and GSTT1 Genetic Polymorphisms and Breast Cancer Risk in Selected Filipino Cases

Background: The association of genetic polymorphisms with cancer development has been shown to be race- andtumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genesare associated with breast cancer among selected Filipinos. Methods: A total of 136 histologically confirmed breastcancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from bloodsamples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results:The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantlydifferent (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that riskfor breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion: This study suggests that variants of GSTM1 and GSTT1may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when thesegenotypes were combined with lifestyle or environmental factors.     

Cigarette smoking,glutathione-s-transferase M1 and t1 genetic polymorphisms,and breast cancer risk (United States)

Objective: It has been suggested that functional polymorphisms in genes encoding tobacco carcinogen-metabolizing enzymes may modify the relationship between tobacco smoking and breast cancer risk. We sought to determine if there is a gene–environment interaction between GSTM1 (GSTM1A and GSTM1B), and GSTT1 genotypes and cigarette smoking in the risk of breast cancer. Methods: Cases and controls were recruited in a case–control study conducted in Connecticut from 1994 to 1998. Cases were histologically confirmed, incident breast cancer patients, and controls were randomly selected from women histologically confirmed to be without breast cancer. A total of 338 cases and 345 controls were genotyped for GSTM1 and GSTT1. Results: None of the GSTM1 genotypes, either alone or in combination with cigarette smoking, was associated with breast cancer risk. There was, however, a significantly increased risk of breast cancer among postmenopausal women with a GSTT1 null genotype (OR = 1.9, 95% CI 1.2–2.9). There were also indications of increased risk of breast cancer associated with cigarette smoking for postmenopausal women with GSTT1-null genotype, especially for those who commenced smoking before age 18 (OR = 2.9, 95% CI 1.0–8.8). Conclusion: Women with a GSTT1-null genotype may have an increased breast cancer risk, especially postmenopausal women who started smoking at younger ages.     

Glutathione S-transferase M1 and T1 genetic polymorphisms,alcohol consumption and breast cancer risk

Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case-control study in the state of Connecticut in the period 1998 and 2001. Cases were histologically confirmed, incident breast cancer patients in New Haven County, CT. Controls were randomly selected from women histologically confirmed to be without breast cancer. The study results show that, while GSTM1 genotypes were not associated with breast cancer risk, GSTT1-null genotype was associated with a significant 90% increased risk for postmenopausal women (OR=1.9, 95% CI 1.2-3.0). Analysis by GST genotypes and alcohol consumption shows that GSTM1A ever-drinking women had a 2.5-fold (OR=2.5, 95% CI 1.1-5.5) increased risk of breast cancer compared to the GSTM1A never-drinkers, and the risk increases with duration and daily amount of alcohol consumption. Postmenopausal women with GSTT1-null genotype, who consumed a lifetime of >250 kg of spirit-equivalents, had an almost seven-fold increased risk (OR=6.8, 95% CI 1.4-33.9), and drinking commencing at younger ages appears to carry a higher risk. An OR of 8.2 (95% CI 1.2-57.4) was observed for those with GSTM1A, and GSTT1-null genotypes who had consumed a lifetime of >250 kg of spirit-equivalents. In conclusion, alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes.     

N-acetyltransferase (NAT1, NAT2) and glutathione S-transferase (GSTM1, GSTT1) polymorphisms in breast cancer

To evaluate the potential association between NAT1/NAT2 polymorphisms and breast cancer, a case-control study was conducted in Korean women (254 cases, 301 controls). NAT1 *4/*10 genotype (42%) was the most common NAT1 genotype in this Korean population. The frequencies of slow, intermediate and rapid NAT2 acetylator genotype were 16, 39 and 44% in cases and 16, 42 and 42% in controls. Neither NAT1 rapid (homozygous or heterozygous NAT1 *10) (OR=1.2, 95% CI=0.8-1.9) nor NAT2 rapid acetylator genotype (OR=1.2, 95% CI=0.8-1.7) showed significant association with breast cancer risk. Although the risk of NAT2 rapid acetylator genotype in postmenopausal women (OR=1.4, 95% CI=0.7-2.8) was higher than that in premenopausal women (OR=1.1, 95% CI=0.7-1.7), those were not statistically significant. However, combinations of NAT1, GSTM1 and GSTT1 genotypes showed a significant linear gene-dosage relationship with breast cancer (p for trend=0.04) and those women with NAT2 rapid acetylator and both GSTM1 and GSTT1 null genotypes were at the elevated risk (OR=3.1, 95% CI=1.0-9.1). These results suggest that genetic polymorphisms of NAT1 and NAT2 have no independent effect on breast cancer risk, but they modulate breast cancer risk in the presence of GSTM1 and GSTT1 null genotypes.     

Glutathione S-transferase T1 and M1 gene defects in ovarian carcinoma

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. The gene defect of GSTT1 has been reported to be associated with an increased risk of myelodysplastic syndromes, astrocytoma and meningioma. A lack of GSTM1 was associated with tobacco smoke-induced lung and bladder cancer. In this study we examined whether the GSTT1 and/or GSTM1 homozygous null genotypes were associated with an increased risk of ovarian cancer using a multiplex polymerase chain reaction protocol. The GSTT1 null genotype was observed in 14% of the control subjects that had never suffered from neoplastic disease (n=115) and in 16% of the patients affected with ovarian cancer (n=103, OR 0.87, 95% CI 0.39–1.92, P=0.73). A lack of GSTM1 was observed in 38% of the control subjects and in 46% of the patients (OR 0.77, 95% CI 0.44–1.32). This difference was not significant (P=0.34). Similarly, no significant differences were obtained if GSTT1 and/or GSTM1 null genotypes were analyzed in subgroups of control subjects and ovarian cancer patients between the ages of 20–40, 41–70 and 71–90 years and in individuals with a positive family history of neoplastic disease. GSTT1 and/or GSTM1 null genotypes were not significantly associated with the histologic type and grade or FIGO (International Federation of Gynecology and Obstetrics) stages of the ovarian carcinomas. In conclusion, GSTT1 and/or GSTM1 null genotypes are not markers for an increased risk of ovarian cancer.     

Meta-analysis of the association between GSTM1 and GSTT1 gene polymorphisms and cervical cancer

Aim: We conducted a meta-analysis to analyze the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer risk, and explore gene-environment interactions. Methods: Identification of relevant studies was carried out through a search of Medline and the EMbase up to Oct. 2011. All case-control studies that investigated the association between GSTM1 and GSTT1 gene polymorphisms and risk of cervical cancer were included. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Results: A total of 21 case-control studies were included in the meta-analysis of GSTM1 (2,378 cases and 2,639 controls) and GSTT1 (1,229 cases and 1,223 controls) genotypes. The overall results showed that the GSTM1 null was related to an increased risk of cervical cancer (OR=1.50, 95% CI=1.21-1.85). Subgroup analysis were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had a moderate increased risk of cervical cancer (OR=1.85, 95% CI=1.07-3.20). For the ethnicity stratification, moderate significantly increased risk of null GSTM1 genotype was found in Chinese (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88), but no increased risk was noted in others. Conclusion: This meta-analysis provided strong evidence that the GSTM1 genotype is associated with the development of cervical cancer, especially in smokers, and Chinese and Indian populations. However, no association was found for GSTT1 null genotype carriers.     

A systematic approach to analysing gene-gene interactions: polymorphisms at the microsomal epoxide hydrolase EPHX and glutathione S-transferase GSTM1, GSTT1, and GSTP1 loci and breast cancer risk.

OBJECTIVE: We undertook a case-control study in an Australian Caucasian population-based sample of 1,246 cases and 664 controls to assess the roles of detoxification gene polymorphisms EPHX T>C Tyr(113)His, GSTT1 deletion, GSTM1 deletion, and GSTP1 A>G Ile(105)Val on risk of breast cancer. METHODS: We systematically addressed the main effects and possible gene-gene interactions using unconditional logistic regression to estimate odds ratios (OR) adjusted for potential confounders and using standard model building approaches based on likelihood theory. RESULTS: There was a decreased risk associated with the EPHX CC genotype [OR, 0.60; 95% confidence interval (95% CI), 0.43-0.84; P = 0.003], marginally significant evidence of increased risk with GSTM1 null genotype (OR, 1.21; 95% CI, 1.00-1.47; P = 0.05), but no association with GSTT1 null genotype (OR, 1.12; 95% CI, 0.86-1.45; P = 0.4) or GSTP1 (OR, 0.95; 95% CI, 0.82-1.10; P = 0.5) genotype. The full model with all interactions gave a significantly better fit than a main-effects-only model (P < 0.001), providing evidence for gene-gene interactions. The most parsimonious model included main effects for EPHX, GSTT1, and GSTM1; a two-way interaction between EPHX and GSTM1; and a three-way interaction between EPHX, GSTM1, and GSTT1. Predicted risks were greatest for women carrying deletions of both GSTT1 and GSTM1, with either the EPHX TC genotype (OR, 2.02; 95% CI, 1.19-3.45; P = 0.009) or EPHX CC genotype (OR, 3.54; 95% CI, 1.29-9.72; P = 0.14). CONCLUSION: Detoxification gene polymorphisms may interact with each other to result in small groups of individuals at modestly increased risk. We caution against overinterpretation and suggest that pooling of similarly large studies is needed to clarify the possible role of such complex gene-gene interactions on breast cancer risk. 2007;16(4):769-74).     

Glutathione-S-transferase (GSTM1, GSTT1) Null Phenotypes and Risk of Lung Cancer in a Korean Population

Purpose: The aim of this study was to evaluate any association of GSTM1 and GSTT1 null genotypes withthe risk of lung cancer in a South Korean population. Methods: We conducted a large-scale, population-basedcase-control study including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and GSTT1 weredetermined using real-time polymerase chain reaction. Results: In logistic regression analysis adjusted for age andsmoking, we did not find any association between GSTM1 or GSTT1 and LC risk in women. However, in men,the GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95% CI=0.99-1.41 forGSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1 and GSTT1 null genotypes conferredan increased risk for LC in men (OR=1.39, 95% CI=1.08–1.78). The OR for the GSTT1 null genotype was greaterin subjects aged 55 years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97–1.90for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men; OR=0.86, 95% CI=0.66–1.12 forwomen) in both genders (p for interaction <0.05). Conclusions: In the Korean population, the GSTM1 andGSTT1 null genotypes are risk factors for LC in men; the GSTT1 null genotype has a more prominent effecton LC risk in younger people (age 55 years and under) than in older individuals.     

谷胱甘肽转移酶T1和M1基因多态性及吸烟与结直肠癌关系的对照研究

目的　研究谷胱甘肽转移酶 (GSTs)M1、T1基因多态性与结直肠癌易感性的关系。方法12 6例结直肠癌患者和 343例随机抽样的正常对照者 ,应用多重聚合酶链反应 (PCR)方法检测其GSTM1和GSTT1基因多态性 ,采用非条件Logistic回归模型分析基因型、吸烟情况与结直肠癌患病的关系。结果　GSTM1和GSTT1缺陷型基因型在对照人群中的频率分布为 5 5 .5 %和 2 0 .4 %。在GSTT1缺陷型基因型的人群中 ,GSTM1缺陷型患直肠癌风险是非缺陷型者的 9.74倍 (95 %CI为 1.13～83.85 )。现在吸烟者中 ,GSTM1缺陷型基因型患结肠癌的风险是非缺陷型者的 2 .2 2倍 (P >0 .0 5 ) ;GSTT1缺陷型基因型患结肠癌的风险是非缺陷型者的 4 .5 5倍 (95 %CI为 1.14～ 18.17) ,患直肠癌的风险是非缺陷型者的 4 .6 0倍 (95 %CI为 1.11～ 19.11)。结论　GSTM1和GSTT1缺陷型基因型有可能增加结直肠癌的危险性 ,其危险性主要表现在两者的联合作用上 ;环境暴露因素———吸烟和相关代谢酶多态性也表现出增加结直肠癌危险性的联合作用。     

GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk

Glutathione S-transferases (GSTs) are a family of important enzymes involved in the detoxification of a wide variety of known and suspected carcinogens, including potential mammary carcinogens identified in charred meats and tobacco smoke. A substantial proportion of the Caucasian population has a homozygous deletion (null) of the GSTM1 or GSTT1 gene, which results in lack of production of these isoenzymes. We conducted a case-control study in a cohort of postmenopausal Iowa women who in 1986 completed a mailed questionnaire on lifestyle factors including information on cigarette smoking and breast cancer risk factors. DNA samples and information related to charred meat intake were obtained, in the case-control study, from breast cancer cases diagnosed during 1992–1994, and a random sample of cancer-free cohort members. Included in this study were 202 cases and 481 controls who were genotyped for GSTM1 or GSTT1 gene polymorphisms. Compared to women who had both GSTM1 and GSTT1 genes, a 60% elevated risk (95% CI = 1.0–2.5) was observed among those whose GSTM1 or GSTT1 gene was deleted. When stratified by meat eating habits, the risk of breast cancer associated with null GSTM1 or GSTT1 genotype was observed primarily among women who ate meats consistently well- or very well-done. Women who carried either one of the null genotypes and consumed meat consistently well- or very well-done had a 3.4-fold elevated risk of developing breast cancer (95% CI = 1.6–7.1). Cigarette smoking was not a risk factor for breast cancer among women who had either the GSTM1 or GSTT1 genes. Among those with the null GSTT1 genotype, however, a significantly elevated risk of breast cancer was associated with cigarette smoking (OR = 2.5, 95% CI = 1.1–5.4) and the association was stronger among former (OR = 4.4, 95% CI = 1.5–12.8) than current smokers (OR = 1.3, 95% CI = 0.4–4.1). This study suggests that certain null GST genotypes may be associated with an elevated risk of breast cancer and the association may be modified by charred meat intake and cigarette smoking.     

GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking

The impact of genetic polymorphisms in GSTM1, GSTP1 or GSTT1 on susceptibility to lung cancer has received particular interest since these enzymes play a central role in detoxification of major classes of tobacco carcinogens. In the current German study we investigated the role of GSTM1, GSTT1 and GSTP1 polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes especially in relation to tobacco smoking. The GSTM1, the GSTP1 as well as GSTT1-polymorphism were determined by real time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies of the GSTP1 polymorphism in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients, who carried at least one mutant variant allele of GSTP1 (OR=1.03; 95%-CI: 0.76-1.39) did not show any elevated risks. GSTM1 or GSTT1 null-genotypes were found in 47.3% resp. 18.5% of the controls and in 52.5% resp. 16.8% of the cancer patients. The estimated risk of the GSTM1 null genotype for lung cancer was OR=1.34 (95%-CI: 0.99-1.81) and for the GSTT1 null genotype OR=0.88 (95%-CI: 0.59-1.32). When analyzed by histology no individual subtype of lung cancer was strongly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption confirming the association with smoking-related lung cancer risk. Stratified analysis between tobacco smoking and variant genotypes revealed for heavy smokers (>60 pack-years) increasing risks at the presence for at least one copy of the GSTP1 variant allele OR=50.56 (95%-CI: 15.52-164.79). The corresponding risks for GSTM1 null genotypes were OR=112.08 (95%-CI: 23.02-545.71) and for the GSTT1 null-genotype OR=158.49 (95%-CI: 17.75-1415.06) in smokers >60 pack-years. Analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study polymorphisms of the GSTM1, GSTT1 or GSTP1 had no relevant modifying effect on lung cancer risk and cumulative smoking dose.     

Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis.

PURPOSE: We studied the relation of breast cancer to common deletion mutations in GSTM1 and GSTT1 and the functional Ile(105)Val polymorphism in GSTP1 in a large, population-based case-control study conducted in China and performed a meta-analysis to summarize the literature. EXPERIMENTAL DESIGN: In the case-control study, a total of 1144 breast cancer cases and 1221 community controls were genotyped for GSTM1, GSTP1, and GSTT1 using PCR-based methods. Associations of genotypes and breast cancer were evaluated in logistic regression models. Meta-analysis odds ratios (ORs) were estimated using a fixed effects model. RESULTS: In the case-control study, associations were null for GSTM1 [age-adjusted OR 0.97, 95% confidence interval (CI): 0.82-1.14] and GSTT1 (OR 0.97, 95% CI: 0.83-1.15). A significant increase in risk was observed among homozygotes for the variant Ile(105)Val polymorphism (OR 1.92, 95% CI: 1.21-3.04). No combined effects of GSTM1, GSTP1, and GSTT1 genotypes or interactions with potential effect modifiers were detected. All results were similar in pre- and postmenopausal women and for early versus advanced stage breast cancer. The meta-analysis, based predominantly on Caucasian women, supported null results for the homozygous deletion variant in GSTM1 (summary OR 1.05; combining 19 studies) and GSTT1 (summary OR 1.11; 15 studies). Meta-analysis results for the homozygous GSTP1 variant indicated no overall association (summary OR 1.04; 10 studies), although results varied significantly across studies (P = 0.009). CONCLUSIONS: This large case-control study provides strong support for earlier studies showing no overall association of the GSTM1 and GSTT1 deletion polymorphisms with breast cancer risk. The GSTP1 variant may be relevant to breast cancer risk in Asian populations.     

Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore

We have previously found marine n-3 fatty acids to be inversely related to post-menopausal breast cancer in Chinese women from Singapore. Post-menopausal women with high [quartiles 2-4 (Q2-Q4)] versus low [quartile 1 (Q1)] intake exhibited a statistically significant reduction in risk of breast cancer after adjustment for potential confounders [relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.50, 0.87]. Experimental studies have demonstrated a direct role for the peroxidation products of marine n-3 fatty acids in breast cancer protection. There is a suggestion that the glutathione S-transferases (GSTs) may be major catalysts in the elimination of these beneficial by-products. Therefore, we hypothesized that individuals possessing the low activity genotypes of GSTM1, GSTT1 and/or GSTP1 (i.e. the GSTM1 null, GSTT1 null and GSTP1 AB/BB genotypes, respectively) may exhibit a stronger marine n-3 fatty acid-breast cancer association than their high activity counterparts. The Singapore Chinese Health Study is a prospective investigation involving 35,298 middle-aged and older women, who were enrolled between April 1993 and December 1998. In this case-control analysis, nested within the Singapore Chinese Health Study, we compared 258 incident breast cancer cases with 670 cohort controls. Overall, breast cancer risk was unrelated to GSTM1 and GSTP1 genotypes. However, the GSTT1 null genotype was associated with a 30% reduced risk of breast cancer [odds ratio (OR) = 0.71, 95% CI = 0.52, 0.96]. Among women with high activity GST genotypes (i.e. GSTM1 positive, GSTT1 positive and GSTP1 AA), no marine n-3 fatty acid-breast cancer relationships were observed in either pre-menopausal or post-menopausal women at baseline. However, post-menopausal women possessing the combined GSTM1 null and GSTP1 AB/BB genotypes showed a statistically significant reduction in risk after adjustment for potential confounders (Q2-Q4 versus Q1, OR = 0.36, 95% CI = 0.14, 0.94). A similar relationship was observed among women with the combined GSTT1 null and GSTP1 AB/BB genotypes (OR = 0.26, 95% CI = 0.08, 0.78).     

Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk

Isothiocyanates are anticarcinogenic phytochemicals found in cruciferous vegetables that both induce and are substrates for the gluthatione S-transferases (GSTs). The GSTs are phase II metabolizing enzymes involved in metabolism of various bioactive compounds. Functional polymorphisms in GST genes have been identified and may interact with cruciferous vegetable intake to affect cancer risk. We examined this hypothesis using data from the Long Island Breast Cancer Study Project, a population-based case-control study conducted in Long Island, NY, from 1996 to 1997. Cruciferous vegetable intake in the previous year was assessed via modified Block food frequency questionnaire. DNA was extracted from blood samples (n = 1052 cases and n = 1098 controls) and genotyped for GSTM1 deletion, GSTT1 deletion and GSTP1 Ile105Val using multiplex polymerase chain reaction and Taqman assays. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). We found an 86% increase in the OR for breast cancer among carriers of the GSTM1 null, GSTT1 null and GSTP 105Ile/Ile genotypes (OR = 1.86, 95% CI = 1.12, 3.08) and a 36% decrease in the OR among carriers of GSTM1 present, GSTT1 null and GSTP1 105Ile/Val + Val/Val genotypes (OR = 0.64, 95% CI = 0.42, 0.97) compared with GSTM1 present, GSTT1 present and GSTP1 105Ile/Ile carriers. We found no joint effects among GST polymorphisms and cruciferous vegetable intake and breast cancer risk. In conclusion, we found associations between specific combinations of three GST gene polymorphisms and breast cancer risk but these did not modify the association between cruciferous vegetable intake and breast cancer. Additional studies are needed to confirm the associations observed.     

Glutathione S-transferase gene polymorphisms and risk of gastric cancer in a Chinese population

Aim: The potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in risk of gastric cancer in Chinese was studied. Methods: We collected 194 gastric cancers by pathologic examination and 412 controls from southern China during January 2007 to January 2011. Genotyping was based upon duplex polymerase-chain-reaction withthe PCR-CTPP method. Results: Individuals carrying null GSTM1 and GSTT1 had 1.49 and 1.96 fold risk sof gastric cancer when compared with respective non-null genotypes. We also found a non-significant 37% excess risk of gastric cancer among carriers of GSTP1 1b/1b genotype when compared with 1a/1a genotype (OR=1.37, 95% CI=0.81-2.25). The combination of null/null GSTM1 and GSTT1 genotypes showed higher increased risk of gastric cancer (OR=3.17, 95% CI=1.68-4.21). Moreover, cancers in ever smokers and ever drinkers were observed to be strongly associated with null GSTM1 and GSTT1, and a significant cancer risk was observed in positive H.pylori infection individuals with null GSTT1. Conclusion: Our study provided evidence that genetic deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to gastric cancer in our Chinese population, while the GSTP1a/b polymorphism may not.     

GSTT1, GSTM1 and GSTP1 genetic polymorphisms and interaction with tobacco, alcohol and occupational exposure in esophageal cancer patients from North India

Glutathione S-transferases(GSTs) are detoxification enzymes that provide critical defense against carcinogens. Our hypothesis was that altered frequencies of GST genotypes and environmental exposures might be associated with increased susceptibility for the development of esophageal cancer. A total of 100 esophageal cancer patients and 137 age and gender matched healthy controls were analyzed for GST polymorphisms. Frequencies of GSTT1 null, GSTM1 null and GSTP1 genotypes did not differ between patients and controls. However, a two-fold risk was observed for GSTM1 null genotype in adenocarcinoma (OR(odds ratio) 2.1; 95% CI(confidence intervals)=0.53-8.6). Further, we used a case only design to study gene-environment interactions in esophageal cancer. In patients with smoking habits, GSTM1 null and GSTP1 ile/ile genotype were at higher risk for esophageal cancer (OR 1.5; 95% CI=0.50-4.4 and OR 1.3; 95% CI=0.40-3.5), respectively. A moderate risk for cancer was observed from alcohol usage along with GSTM1 null(OR 1.3; 95% CI=0.50-3.6) and GSTP1 val/val genotypes(OR 1.2; 95% CI=0.20-5.7). Interaction of GST genotypes with occupational exposure did not affect risk for esophageal cancer. These findings suggest that genetic polymorphisms of GSTT1, GSTM1, and GSTP1 are not associated with higher risk of esophageal cancer. However, interaction of smoking or alcohol with GSTM1 null or GSTP1 ile/ile moderately increases the risk for esophageal cancer in North Indian population.     

Prognostic potential of glutathione S-transferase M1 and T1 null genotypes for gastric cancer progression

To improve understanding of glutathione S-transferase (GST) behavior in terms of a development and prognostic factor for gastric adenocarcinoma, we investigated the association between the GSTM1 and GSTT1 null genotypes and gastric cancer risk or the prognostic value of the GSTM1 and GSTT1 null genotypes was evaluated. Using a polymerase chain reaction-based method, the frequencies of GSTM1 and GSTT1 genotypes and prognostic factors, such as staging, differentiation, and histologic type (intestinal vs. diffuse), were evaluated in 80 patients with curatively resected primary gastric adenocarcinoma. The frequencies of GSTM1 and GSTT1 null individuals were higher in the gastric cancer group, but the differences were not statistically significant (for GSTM1 null odds ratio (OR)=0.86; 95% confidence interval (CI)=0.49-1.51 and for GSTT1, OR=0.97; 95% CI=0.55-1.71). Since the GSTM1 and GSTT1 null genotypes are potential indicators of gastric adenocarcinoma, we examined the relationship between the GSTM1 and GSTT1 genotypes and prognostic factors. In terms of the histologically diffuse type of cancer, GSTM1 indicated an approximately 3.24-fold increase (OR=3.24; 95% CI=1.05-10.17). With respect to gastric cancer differentiation, the frequency of the GSTM1 null genotype was linked with a statistically significant increase in risk (3.42-fold) for the high-grade type (OR=3.42; CI=1.02-13.24). Our results indicate that there is no obvious relationship between GSTM1 and GSTT1 polymorphisms and the development of gastric cancer. However, in Korean gastric adenocarcinoma patients the GSTM1 null genotype appears to be associated with a poorer prognosis.     

Genetic Deletions of GSTM1 and GSTT1 in Head and Neck Cancer: Review of the Literature from 2000 to 2012

Head and neck cancer is one of the leading causes of deaths worldwide. Two genes GSTM1 and GSTT1 involvedin phase II of carcinogen detoxification have been frequently studied in the literature. Their null genotypes arethought to be associated with increased head and neck cancer risk. However, the published reviews are not upto date and many important papers have been skipped. The current literature review was restricted to the nullgenotypes of the GSTM1 and GSTT1 genes with special emphasis on the genotypic status. We found that thesize of study sample varied greatly and the oral cavity cancer was more influenced by GSTM1 and GSTT1 genedeletions. With respect to ethnicity Asians are more prone to head and neck cancers with these null genotypes ascompared to Europeans and Americans. The current review showed significant associations (OR=9.0, 95%CI;1.4-9.5; OR=3.7, 95%CI; 1.4-9.5) of GSTM1 and GSTT1 null genotypes with head and neck cancers. Reviewconfirms the data of previous reviews that GSTM1 and GSTT1 gene polymorphisms may be risk factors forcancer initiation.     

GSTM1、GSTT1基因多态性和吸烟与膀胱癌关系的病例对照研究

目的:应用全人群为基础的病例对照研究探讨GSTM1、GSTT1基因多态性和吸烟与膀胱癌危险性的关系。方法:采用多重PCR方法对404例正常对照和414例膀胱癌病例的基因组DNA进行GSTM1和GSTT1基因分型,应用非条件logistic回归分析方法进行统计分析。结果:与携带GSTM1( )基因型者比,GSTM1(-)基因型的男、女性患膀胱癌危险性分别为1.66(95%CI:1.18～2.33)和1.08(95%CI:0.59～1.98)。同样携带GSTM1(-)基因型,吸烟者比不吸烟者患膀胱癌的危险性更加明显。与不吸烟且携带GSTM1( )基因型男性比,GSTM1(-)基因型的目前吸烟者的OR值为2.99(95%CI:1.56～5.74),而携带GSTM1(-)基因型同时吸烟年限≥40年者OR为4.33(95%CI:2.14～8.73)。尽管女性吸烟例数较少,但携带GSTM1(-)基因型的吸烟女性患膀胱癌危险性显著高于不吸烟的GSTM1( )基因型者,OR值为6.72(95%CI:1.69～26.80)。与不吸烟且携带GSTT1( )基因型男性相比,携带GSTT1(-)基因型的吸烟者患男性膀胱癌危险的OR值为1.38(95%CI:0.79～2.42)。携带GSTT1(-)基因型的吸烟女性患膀胱癌危险性是不吸烟的GSTT1( )基因型者的3.04倍(95%CI:0.77～12.01)。结论:GSTM1(-)基因型能显著增加男性患膀胱癌的风险,该基因型与吸烟可能有一定的联合作用。GSTT1基因型可能与上海市区男、女性膀胱癌无关。