Polymorphisms in GSTM1, GSTTI and GSTP1 and nasopharyngeal cancer in the east of China: a case-control study

Aim: The study was performed to assess the potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in the risk of nasopharyngeal cancer in Chinese population. Method: We collected 182 cases undergoing pathologic examination and 366 controls from the affiliated hospital of Medical College of Qingdao University from April 2006 to July 2010. Genotyping was based upon duplex polymerase-chain-reactions with the PCR-CTPP method. Results: More smokers were found in NPC patients than controls, and a higher IgA/VCA+ . Individuals carrying null GSTM1 and GSTT1 had 1.76 and 2.01 fold risk of NPC when compared with non-null genotypes, respectively. A non-significant increase risk of NPC was found in individuals with 1b/1b genotype when compared with 1a/1a genotype (OR=1.32, 95%CI=0.60-2.94). When compared with non-null GSTM1 and GSTT1 genotypes, the combination of null/null GSTM1 and GSTT1 genotypes showed moderate increased risk of NPC (OR=3.03, 95% CI=1.74-5.08). Conclusion: Our study provides evidence that genetic deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to NPC in Chinese population, while GSTP1 may not. Our findings provide information relevant to the prevention of NPC.     

Glutathione S-transferase gene polymorphisms and risk and survival of pancreatic cancer

BACKGROUND.

Pancreatic cancer is a multifactorial disease with metastasis‐prone and therapy‐resistant nature. The authors hypothesized that genetic variants of glutathione S‐transferase (GST) affect detoxification of carcinogens and anticancer agents in the human pancreas and, thus, the risk and survival of pancreatic cancer.

METHODS.

Genotypes of GSTM1, GSTT1, and GSTP1 were determined in 352 patients with pancreatic ductal adenocarcinoma and in a control group of 315 healthy, non‐Hispanic whites (frequency‐matched by age and sex). Survival analysis was performed in a subset of 290 patients. Epidemiological and clinical information was obtained. A multiple unconditional logistic regression model, a Cox proportional hazards model, and log‐rank tests were used for statistical analysis.

RESULTS.

No significant main effects of any of 3 GST genes on the risk of pancreatic cancer were observed. Subgroup analysis showed that older individuals (aged ≥62 years) who carried the GSTP1*C (¹⁰⁵Val‐¹¹⁴Val) containing genotype tended to have a reduced risk compared with younger individuals who carried the non‐*C genotype (for sex and pack‐years of smoking, the adjusted odd ratio was 0.54; 95% confidence interval [95% CI], 0.29–1.02). In a survival analysis of 138 patients who received 5‐flurorouracil, patients who carried the GSTP1*C containing genotype had a significantly longer survival than patients who carried the non‐*C genotype (multivariate hazard ratio, 0.45; 95% CI, 0.22–0.94).

CONCLUSIONS.

The GSTP1*C variant conferred a possible protective effect against pancreatic cancer in older individuals and a significant survival advantage in patients who received 5‐florouracil. The current findings must be confirmed before further inferences can be made. Cancer 2007 © 2007 American Cancer Society.     

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk

Objectives: The human GSTTP1 gene is polymorphic with an A G transition in exon 5 causing a replacement 105 IleVal in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.     

Glutathione S-transferase T1 null-genotype is associated with an increased risk of lung cancer

Glutathione S-transferases (GSTs) are involved in detoxification of carcinogens, e.g., from tobacco smoke. Therefore, polymorphisms in the GST genes have been considered as potential modifiers of individual cancer risk. In a population-based case-cohort study where cases and the subcohort sample were matched on duration of smoking, we investigated the occurrence of lung cancer and histological subtypes of lung cancer in relation to deletion polymorphism in both GSTM1 and GSTT1, single nucleotide polymorphisms (SNPs) in GSTP1 (Ile105Val and Ala114Val) and a 3 base pair deletion polymorphism in GSTM3. We further investigated the effects of the GST polymorphisms on lung cancer risk within subgroups of subjects defined by gender and age. The results showed a 2.4-fold (CI = 1.31-4.41) increased risk of lung cancer in GSTT1 null-genotype carriers but no significant effects of the polymorphisms in GSTM1, GSTM3, GSTP1-105 or GSTP1-114. The association was strongest in lower age groups, with a 9.6-fold increase in risk for subjects with the GSTT1 null-genotype in the 50-55 years age interval (CI = 3.03-30.59). Positive associations were found for GSTT1 within all major histological subtypes. Squamous cell carcinoma was the histological type most strongly associated with the GSTT1 genotype, with a 5.0-fold (CI = 2.26-11.18) increase in risk for subjects carrying the GSTT1 null-genotype. The effects of the GSTT1 null-genotype seemed stronger in the presence of the GSTM1 null-genotype or the GSTP1-105 variant allele. These results suggest that the GSTT1 null-genotype is associated with an increased risk of lung cancer, especially in younger individuals.     

Glutathione S-transferase Polymorphisms and Bone Tumor Risk in China

Aim: We aimed to study the potential role of GSTM1 and GSTT1 in the risk of osteosarcoma in Chinese population. Methods: We collected 110 osteosarcomas by pathologic examination and 226 controls from the First Affiliated Hospital of Harbin Medical University during December 2008 to December 2010. Genotyping was based upon duplex polymerase-chain-reaction with the PCR-CTPP method. Results: Individuals carrying null GSTM1 and GSTT1 had 1.50 and 2.07 fold risks of osteosarcoma when compared with non-null genotypes, respectively. The increased risk associated with the GSTT1 polymorphism seemed more evident among males (Null GSTT1 genotype vs. non-null genotype, adjusted OR= 2.43, 95% CI: 1.29-3.30) than females (adjusted OR =1.66, 95% CI: 1.02-2.78). The increased risk was also more evident among individuals aged 15 years or less (adjusted OR for null GSTT1 genotype vs. non-null genotype = 2.24, 95% CI: 1.20-3.24) than those aged more than 15 years (adjusted OR = 1.82, 95% CI: 1.07-2.95). Conclusion: Our study of the association between polymorphisms in GSTM1 and GSTTI and the risk of osteosarcoma in a Chinese population provided evidence that null GSTTI might be a useful marker of susceptibility to osteosarcoma development, especially for male sand young age individuals.     

GSTP1 polymorphisms and gastric cancer in a high-risk Chinese population

Objectives: In a population-based case–control study in Yangzhong, China, we investigated the relationship between genetic polymorphisms of GSTP1 and susceptibility to gastric cancer and its premalignant lesion, chronic gastritis. The possible gene–gene interactions between GSTP1 polymorphisms and GSTM1, GSTT1 genes were explored. Methods: Epidemiologic data were collected by standard questionnaire from 133 gastric cancer cases, 166 chronic gastritis cases, and 433 cancer-free population controls. Blood samples for Helicobacter pylori and molecular marker assays were collected from 84 gastric cancer cases, 146 chronic gastritis, and 429 population controls. GSTP1 polymorphisms were determined by the PCR-RFLP method and H. pylori infection was measured by the ELISA method. Associations between certain GSTP1 genotypes and both gastric cancer and chronic gastritis were assessed by odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression. Results: The distributions of three GSTP1 genotypes, Ile/Ile, Ile/Val, and Val/Val, were similar in gastric cancer cases, chronic gastritis, and controls. After adjusting for age, gender, education, body mass index, pack-year of smoking, alcohol drinking, H. pylori infection, salt and fruit intakes, the adjusted ORs of Val/Val were 1.3 (95% CI: 0.1–11.2) for gastric cancer and 0.9 (95% CI: 0.2–4.8) for chronic gastritis. Combining the Val alleles (Val/Val and Ile/Val) into one group, no association was observed between GSTP1 and both gastric cancer and chronic gastritis. In addition, the allelism at the GSTP1 locus did not increase gastric cancer and chronic gastritis risks associated with the GSTM1 or GSTT1 genotypes. Conclusion: Our data suggest that the GSTP1 genotype seems not to be associated with the risk of gastric cancer and chronic gastritis in a high-risk Chinese population.     

An updated pooled analysis of glutathione S-transferase genotype polymorphisms and risk of adult gliomas

Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in thedetoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studiesinvestigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors havereported conflicting results. The rationale of this pooled analysis was to determine whether the presence of aGST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In ourmeta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT andEMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1Ile105Val. Between-study heterogeneity was assessed using χ2-based Q statistic and the I2 statistic. Crude oddsratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association betweenGSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesisshowed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 orGSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively;95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggestany strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adultgliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history onglioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potentialconfounding factors are needed to confirm these results.     

Glutathione S-transferase M1 and T1 status and the risk of laryngeal cancer: a meta-analysis

Background: Polymorphic variations in GSTM1 and GSTT1 have been implicated as risk factors for various cancers. A number of studies conducted to assess their association with susceptibility to laryngeal carcinomas have yielded inconsistent and inconclusive results. In the present study, the possible association of laryngeal cancer risk with GSTM1 and GSTT1 null genotypes was explored by a meta analysis. Method: A meta-analysis was carried out on case-control studies collected from the literature. The pooled odds ratio (OR) and presence of publication bias in those studies were evaluated. Results: A total of 20 studies concerning laryngeal cancer were identified. The results showed that the pooled OR was 1.22 (95% CI 1.03-1.43) for the GSTM1 polymorphism while for GSTT1 polymorphism, the pooled OR was 1.23 (95% CI 0.96-1.58). No evidence of publication bias was detected among the included studies. Conclusion: The results suggest that the GSTM1 deficiency significantly increases susceptibility to laryngeal cancer whereas GSTT1 null genotype might not be a risk factor.     

Dietary intake of Cruciferous vegetables, <Emphasis Type="Italic">Glutathione S-transferase (GST)</Emphasis> polymorphisms and lung cancer risk in a Caucasian population

Objective: To evaluate possible interactions between dietary intake of cruciferous vegetables and the glutathione s-transferase mu and theta (GSTM1 and GSTT1) genotypes in lung cancer risk. Methods: Hospital-based case–control study of 716 Caucasian lung cancer cases and 939 spouse and friend controls conducted in Boston, Massachussetts between 1992 and 2000. Dietary intake was collected through a food frequency questionnaire and blood was obtained for genotyping. Logistic regression models were adjusted for age, gender, total calories and smoking variables. Results: Higher intakes of cruciferous vegetables reduced lung cancer risk among GSTM1 present individuals (odds ratio (OR) _{highest versus lowest tertile} = 0.61, 95% confidence interval (CI) = 0.39–0.95) but not among GSTM1 null individuals (OR _{highest versus lowest tertile} = 1.15, 95% CI = 0.78–1.68). We observed statistically significant interactions between GSTM1 and cruciferous vegetable intake overall (likelihood ratio test (LRT): p = 0.05) and among current smokers (LRT: p = 0.01). No significant interactions were observed for GSTT1 or the combined GSTM1/T1 genotype. Conclusions: In our study, higher cruciferous vegetable intake reduced lung cancer risk only among individuals with the GSTM1 present genotype. Our findings differed from prior studies that specifically assessed isothiocyanates found in cruciferous vegetables or evaluated Asian study populations with higher levels of cruciferous vegetable consumption.     

Genetic Variation of GSTM1, GSTT1 and GSTP1 Genes in a South Indian Population

The glutathione S transferase (GST) family of enzymes play a vital role in the phase II biotransformation ofenvironmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and the polymorphismsin GST genes have been associated with cancer susceptibility and prognosis. Moreover, distinct ethnic differenceshave been observed in the type and frequency of GST gene polymorphisms. Hence, the present study was aimed todetermine the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 255 healthy random volunteers fromSouth India. The GSTM1 and GSTT1 genotypes were determined by PCR and GSTP1 by PCR-RFLP using peripheralblood DNA.The GSTM1 and GSTT1 null genotype frequencies were found to be 22.4% and 17.6% respectively. TheGSTP1 allelic frequency was 0.78 for the Ile allele and 0.22 for the Val allele and the genotype frequency was 58.4%for Ile/Ile, 38.4% for Ile/Val, and 3.1% for Val/Val. Comparison of the frequencies of GST polymorphisms observedin the present study with other Indian and world populations revealed a distinctive nature of the South Indianpopulation with respect to polymorphims at the GST gene loci. A better understanding of carcinogen metabolizinggene distribution should contribute to risk assessment of humans exposed to environmental carcinogens.     

Lack of influence of glutathione S-transferase gene deletions in sporadic breast cancer in Pakistan

Glutathione S-transferases constitute the phase II detoxification enzymes involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. GSTM1 and GSTT1 are polymorphic and their deletions have been found to be associated with breast cancer risk in some of the world populations. The current study was aimed at evaluation of GSTM1 and GSTT1 gene deletions in 150 unrelated breast cancer patients and 150 healthy controls from Pakistani population. Multiplex PCR assay along with CYP1A1 exon 7 as an internal control was used. Our sampled patients and controls had a mean age of 48 (+11.8) and 45 (+7.9) years respectively. The analysis suggested that only 2% breast cancer patient and 8% controls had homozygous GSTM1 gene deletions (OR 0.23, 95% CI 0.06-0.85). A total of 8.7% patients and 18.6% controls had homozygous GSTT1 deletion (OR 0.41, 95% CI 0.25-0.83). The statistical analysis suggest that a non significant number (P>0.05) of individuals compared to controls have GSTM1 and GSTT1 gene deletions. Deletion in both genes was not observed in any of the patients or controls. The present case control study suggests no association of GSTM1 and GSTT1 gene deletions with sporadic form of breast cancer in Pakistani population.     

IL-1RN gene polymorphisms reduces thyroid cancer risk in Chinese Han population

The purpose of this study was to investigate the effect of IL-1RN polymorphisms on thyroid cancer (TC) risk in Han population. Genotypes of four single nucleotide polymorphisms (SNPs) (rs17042888, rs928940, rs3181052, and rs452204) were analyzed by Agena MassARRAY. Meanwhile, we used the logistic regression to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), and significant differences were evaluated by t test and χ² test. Findings found that allele “G” of rs452204 and rs3181052 in interleukin-1 receptor antagonist (IL-1RN) reduced the risk of TC. (OR = 0.72, 95% CI = 0.55-0.94, p = .017; OR = 0.73, 95% CI = 0.56-0.94, p = .017, respectively). Hierarchical analysis indicated that three SNPs (rs17042888, rs3181052, and rs452204) significantly reduced the risk of TC among females or individuals older than 48 years (p < .05). Our findings indicate that IL-1RN polymorphisms may contribute to a protective role against TC risk.     

Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population

Aim: The distribution of DNA repair gene XRCC1 and XRCC3 genotypes was used to assess the potential influence of genetic polymorphisms on risk of colorectal cancer, and interactions with other factors. Methods: a 1:2 matched case-control study was conducted with 485 cases and 970 controls. XRCC1 and XRCC2 genotype polymorphisms were based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. Results:The XRCC1 399Cln allele polymorphism was found to be associated with an increased colorectal cancer risk, while an non-significant inversely association was noted for XRCC3 241Thr/Thr genotype. We also found that individuals with the XRCC1 399 Gln and XRCC3 241Met alleles had an elevated risk, while XRCC3241Thr/Thr was proctective. Conclusion: This study is the first to provide evidence of importance of XRCC1 and XRCC3 gene polymorphisms for risk of colorectal cancer in the Chinese population.     

Glutathione S-transferase M1 and T1 Polymorphisms,Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles.The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned toevaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. Thestudy was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minorgynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attendingthe cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) usingL1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures.Differences in proportions were tested using Pearson’s Chi-square test with Odds ratio (OR) and 95% confidenceinterval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype(OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes wasobserved in women with normal, precancerous and cervical cancerous lesions among ≤35 or >35 years of agegroups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers(OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervicalcancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) andGSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive nonsmokers. The results demonstrate that the GST null genotypes were alone not associated with the developmentof cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.     

Predictive value of excision repair cross-complementing rodent repair deficiency complementation group 1 and ovarian cancer risk

Objective: We aimed to analyze the association between excision repair cross-complementing rodent repairdeficiency complementation group 1 (XRCC1) and ovarian cancer risk. Methods: We performed a hospital-basedcase-control study with 155 cases and 313 controls in China. All Chinese cases with newly diagnosed primaryovarian cancer between May 2005 to May 2010 in our hospital were invited to participate within 2 months ofdiagnosis. Controls were randomly selected from people who requested general health examinations in the samehospital during the same period. SNPs in EXCC1, ERCC1 C8092A and ERCC1 T19007C, were analyzed byPCR-RFLP method. Results: We observed a non-significantly increased risk of ovarian cancer among individualswith ERCC1 8092TT compared with those with the 8092CC genotype (adjusted OR=1.55, 95% CI%=0.74-2.97).Moreover, 19007TT genotype carriers also showed a non-significant increased risk of ovarian cancer over thosewith the 19007CC genotype (adjusted OR=1.78, 95% CI%=0.91-3.64). Conclusion: Our firstly investigationof links between polymorphisms in the ERCC1 gene and the risk of ovarian cancer in Chinese populationdemonstrated no significant association. Further large sample studies in Chinese populations are needed.     

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

Background: The development of cancer results from an imbalance between exposure to carcinogens and the capacity of various enzyme systems engaged in activation or in the detoxification of xenobiotics. The aim of the present study is to investigate the association of GSTP1, GSTM1 and GSTT1 gene polymorphisms in susceptibility to Chronic Myeloid Leukaemia (CML). Methods: A total of 200 CML patients and 100 controls were enrolled in a case-control study with GSTM1 and GSTT1 analysis with PCR and GSTP1 analysis with PCR-RFLP. Results: The GSTT1 null genotype was significantly higher among CML patients suggesting that this genotype is associated with an increased risk of CML. It was found in 42% of cases as compared with 21% of the controls, (OR =2.78, 95% CI: 1.59 - 4.85; p-value =0.000). The presence of the GSTT1 genotype may thus be considered a protective factor for CML. The frequency of individuals carrying GSTM1 null genotype was slightly higher in the control group but this difference was not statistically significant. The GSTM1 null genotype was present in 35% of control cases and 34% of the CML patients, (OR=0.975, 95%CI: 0.58-1.58;p-value=0.863). Individuals with a combined GSTM1 null/GSTT1null genotype had an estimated 2.85-fold increased risk of CML, but no associated risk between GSTP1 Ile 105 Val polymorphism and CML was found (OR=1.99, 95% CI: 0.40 - 9.32; p-value = 0.417). Conclusions: No association between GSTP1 and GSTM1 with susceptibility to CML was found. GSTT1 genotype may be a protective factor for CML, while the null genotype shows association with developing CML.     

Null Glutathione S-transferase T1 and M1 Genotypes and Oral Cancer Susceptibility in China and India - a Meta-analysis

Objective: Genetic variation is considered to strongly impact on detoxification of carcinogens and thereforeis related to cancer risk. However, findings for the null genotypes of GSTT1 and GSTM1 have not always beenconsistent. Therefore the present meta-analysis was conducted. Methods: We accessed the reported study atdifferent research areas and used various databases, including PubMed and Wanfang Med Onlion from 1990to May 1st 2013. We calculated the odds ratio (OR), 95% confidence interval (CI) and P value for oral cancerby using Review Manager 5.1 and STATE 12. Results: We found that there was no increased oral cancer riskamong subjects carrying GSTM1 and GSTT1 null genotype (OR=1.35, 95%CI=0.68-2.68, P=0.39) and (OR=1.41,95%CI=0.72-2.77, P=0.31) in the Chinese population. In contrast, in studies in India a significant correlationbetween GSTM1 null genotype and oral cancer was observed (OR=1.59, 95%CI=1.20-2.11, P=0.001), but not inGSTT1 (OR=1.21, 95% CI = 0.84-1.74, P=0.31). Conclusion: We discovered that GSTM1 deletion polymorphismhad a significant effect on the susceptibility of oral cancer in the Indian population.     

Vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk in a Chinese Han population

The association between vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk is still controversial and ambiguous. The objective of this study was to investigate the association between VEGF gene polymorphisms and gastric cancer risk in Chinese Han patients. We extracted the peripheral blood samples in 150 patients with gastric cancer and 150 controls. Polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) analysis was performed to detect three VEGF gene polymorphisms (?634 G/C, +936 C/T, and +1612 G/A) in these patients. Patients with gastric cancer had a significantly higher frequency of 1612 AA genotype (OR = 6.26, 95% CI = 1.80, 21.85; P = 0.004) than controls. Patients with cardia gastric cancer had a significantly lower frequency of AA (OR = 0.11, 95% CI = 0.01, 0.89; P = 0.04) than those with noncardia gastric cancer. Patients with Lauren's diffuse‐type gastric cancer had a significantly higher frequency of AA (OR = 3.41, 95% CI = 1.22, 9.55; P = 0.02) than those with Lauren's intestinal‐type gastric cancer. The ?634 G/C and +936 C/T gene polymorphisms were not associated with a risk of GC and its progression. This study suggests that the VEGF +1612 G/A gene polymorphisms may be associated with gastric cancer in Chinese Han patients, and that difference in genotype distribution may be associated with the location and Lauren's classification of gastric cancer. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.     

IGlutathione S-transferase (GSTM1 and GSTT1) Polymorphisms in Cervical Cancer in Northeastern Thailand

To evaluate the relationships between genetic polymorphisms of the GSTs (GSTM1 and GSTT1) and cervicalcancer, the null genotype of each gene was studied in squamous cell cervical cancer (SCCA) patients (n=90) andcontrols (n=94) in Northeast Thailand. The prevalence of the GSTM1-null genotype in the controls and SCCApatients was 59.6% and 60.0%, respectively, whereas those of the GSTT1-null genotype in the control andSCCA patients was 40.4% and 46.7%, respectively. Neither of the GST-null genotypes increased the risk forSCCA (p>0.05); however, the combination of the GSTM-1 and GSTT1-null genotypes showed a non-significanttrend to an increased risk for developing cervical cancer with an adjusted OR of 2.7 (95%CI=0.8-9.0, p=0.10).Genetic polymorphisms of GSTM1 and GSTT1 were not significant risk factors for cervical cancer in eithertobacco-smokers or non-smokers. A different contribution of the GST genotype to cancer risk may be attributedto a different, as yet undefined, property of the enzymes.     

Lack of Any Association of GST Genetic Polymorphisms with Susceptibility to Ovarian Cancer - a Meta-analysis

Objective: Epidemiology studies have reported conflicting results between glutathione S-transferase Mu-1 (GSTM1), glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase pi-1 (GSTP1) and ovarian cancer (OC) susceptibility. In this study, an updated meta-analysis was applied to determine whether the deletion of GSTM1, GSTT1 and GSTP1 has an influence on OC susceptibility. Methods: A published literature search was performed through PubMed, Embase, Cochrane Library, and Science Citation Index Expanded database for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity between studies was assessed using the CochraneQ test and I2 statistics. Sub-group analysis was conducted to explore the sources of heterogeneity. Sensitivity analysis was employed to evaluate the respective influence of each study on the overall estimate. Results: In total, 10 published studies were included in the final analysis. The combined analysis revealed that there was no significant association between GSTM1 null genotype and OC risk (OR=1.01, 95%CI: 0.91-1.12). Additionally, there was no significant association between GSTT1 genetic polymorphisms and OC risk (OR=0.98, 95% CI: 0.85-1.13). Similalry, no significant associations were found concerning the GSTP1 rs1695 locus and OC risk. Meanwhile, subgroup analysis did not show a significant increase in eligible studies with low heterogeneity. However, sensitivity analysis, publication bias and cumulative analysis demonstrated the reliability and stability of the current meta-analysis. Conclusions: These findings suggest that GSTs genetic polymorphisms may not contribute to OC susceptibility. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and more specific histological subtypes of OC are needed to prove our findings.