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No association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk: A meta-analysi  [PDF]
Marce-Amara Kpoghomou, Fatch W. Kalembo, Joella Eldie Soatiana
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.34072

Purpose: A number of case-control studies have been conducted to investigate the association of glutathione S-transferase (GST) genetic polymorphisms and endometrial carcinoma risk. However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between polymorphisms on GSTM1, GSTT1 and endometrial carcinoma. Methods: Identification of relevant studies was carried out through a search in the following databases Medline, EMbase andChinaNational Knowledge International (CNKI) up to March. 2013. All case-control studies that investigated the association between GS-TM1 and GSTT1 gene polymorphisms and risk of endometrial cancer were included in the study. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Result: Six published case-control studies of association between the GSTM1 and GSTT1 polymorphism and endometrial cancer risk covering 3558 subjects were included in the metaanalysis, but the results indicated that the null genotypes of GSTM1 and GSTT1 polymorphisms were not associated with a significantly increased risk of endometrial cancer (for GSTM1: OR = 0.99; 95% CI, 0.86 - 1.4; for GSTT1: OR = 0.96; 95% CI, 0.80 - 1.14, respectively). Conclusion: This meta-analysis suggests that GSTM1 and GSTT1 polymorphism may not be associated with increased risk of endometrial cancer. To validate the association between polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed.

The CYP1A1 and GSTM1 Genetic Polymorphisms and Susceptibility to Endometriosis in Women from South India  [PDF]
Roya Rozati,Satyanarayana Reddy B,Simha Baludu Giragalla,Hamid Bakshi
International Journal of Fertility & Sterility , 2009,
Abstract: Background: Endometriosis is one of the most commonly encountered benign problems in gynaecology. It is frequently associated with chronic pelvic pain, dysmenorrhoea, menorrhagia and dyspareunia, which lead to infertility. We determined the possible association between CYP1A1 MspI and GSTM1 null polymorphism in the pathogenesis of endometriosis.Materials and Methods: Ninety seven cases of endometriosis diagnosed by laparoscopy and one hundred two women without endometriosis were laparoscopically confirmed. Genomic DNA of heparinised blood were collected and null gene polymorphisms in GSTM1 and CYP1A1 genes coding for detoxification enzymes were identified by the PCR-based restriction fragment length polymorphism (RFLP) method.Results: The GSTM1 null mutation showed significant association (p<0.03) found between risk of endometriosis and GSTM1 null deletion with an odd ratio (OR) of 2.12, 95% CI: 1.04-4.31.The number of null genotype was more in stage III-IV cases compared to stage I-II. In contrast, we did not find significant association with the CYP1A1 MspI genotype.Conclusion: The study results suggest that women having high risk association with the GSTM1null polymorphism, but no association with the CYP1A1 MspI polymorphism for endometriosis in south Indian women.
CYP1A1, GSTM1 and GSTT1 Genetic Polymorphism in Egyptian Chronic Myeloid Leukemia Patients
Shereen Mahmoud,Dalia A. Labib,Rania H. Khalifa,Reham E. Abu Khalil
Research Journal of Immunology , 2010,
Abstract: The genetic polymorphism of xenobiotic metabolizing enzymes: phase I enzymes; cytochrome P450 (CYP1A1) and phase II enzymes; glutathione S-transferase (GSTM1 and GSTT1), were analyzed in 30 chronic myeloid leukemia patients (CML) (19 females, 11 males; age (Mean±SD) 41.7±9.5 years) and 20 age and sex matched healthy controls. The frequency of CYP1A1 alleles and of GSTT1 and GSTM1 homozygous deletions was examined by PCR- RFLP and PCR methods, respectively, using blood samples. The relationship between these genotypes and risk of CML was assessed by means of Odds Ratio (OR) with 95% confidence limits. Present results showed that the frequency of the mutant allele CYP1A1*2A was found to be 3.3% in CML patients and 45% in controls (OR = 0.042, 95% CI: 0.005-0.373; p<0.001), suggesting that this polymorphic variant may be a protective factor against CML. The frequency of individuals carrying the GSTT1 null genotype was higher among CML patients (60%) compared to controls (15%) (OR = 8.5, 95% CI: 2.038-35.458; p = 0.002). Therefore, GSTT1 null genotype may be a risk factor for CML. Although, GSTM1 null genotype frequency was slightly higher in the patient group (46.7%) than in the controls (40%), this difference was not statistically significant (OR = 1.313, 95% CI: 0.417-4.131; p = 0.642). In conclusion this data suggests that polymorphic CYP1A1 and GSTT1 genes appear to affect susceptibility to CML.
Association between 3801T>C Polymorphism of CYP1A1 and Idiopathic Male Infertility Risk: A Systematic Review and Meta-Analysis  [PDF]
Haiqing Luo, Hongjiao Li, Na Yao, Liren Hu, Taiping He
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086649
Abstract: Background Epidemiological studies have evaluated the association between 3801T>C polymorphism of CYP1A1 gene and the risk for idiopathic male infertility, but the results are inconclusive. We aimed to derive a more precise estimation of the relationship by conducting a meta-analysis of case-control studies. Methods This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase and CNKI databases were searched through November 2013 to identify relevant studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association between CYP1A1 3801T>C polymorphism and idiopathic male infertility risk. Q-test was performed to evaluate between-study heterogeneity and publication bias was appraised using funnel plots. Sensitivity analyses were conducted to evaluate the robustness of meta-analysis findings. Results Six studies involving 1,060 cases and 1,225 controls were included in this meta-analysis. Overall, significant associations between 3801T>C polymorphism and idiopathic male infertility risk were observed in allelic comparison (OR = 1.36, 95% CI: 1.01–1.83), homozygous model (OR = 2.18, 95% CI: 1.15–4.12), and recessive model (OR = 1.86, 95% CI: 1.09–3.20), with robust findings according to sensitivity analyses. However, subgroup analyses did not further identify the susceptibility to idiopathic male infertility in all comparisons. Funnel plot inspections did not reveal evidence of publication bias. Conclusions The current meta-analysis provides evidence of a significant association between CYP1A1 3801T>C polymorphism and idiopathic male infertility risk. Considering the limitation inherited from the eligible studies, further confirmation in large-scale and well-designed studies is needed.
CYP1A1, mEH, and GSTM1 Polymophisms and Risk of Oral and Pharyngeal Cancer: A Spanish Case-Control Study  [PDF]
L. Varela-Lema,A. Ruano-Ravina,M. A. Juiz Crespo,K. T. Kelsey,L. Loidi,J. M. Barros-Dios
Journal of Oncology , 2008, DOI: 10.1155/2008/741310
Abstract: Background. Genetic polymorphisms of drug metabolizing enzymes involved in the detoxification pathways of carcinogenic substances may influence cancer risk. Methods. Case-control study that investigates the relationship between CYP1A1 Ile/Val, exon 4 mEH, and GSTM1 null genetic polymorphism and the risk of oral and pharyngeal cancer examining the interaction between these genes, tobacco, and alcohol. 92 incident cases and 130 consecutive hospital-based controls have been included. Results. No significant associations were found for any of the genotypes assessed. The estimated risk was slightly elevated in subjects with the wild type of the mEH gene and the null GSTM1 genotype. For exon 4 mEH heterozygous polymorphism, the risk was slightly lower for heavy smokers than for light smokers. The inverse association was observed for the GSTM1 null genotype. Conclusions. The results suggest that exon 4 mEH and GSTM1 null polymorphisms might influence oral and pharyngeal cancer.
CYP1A1 MspI and exon7 gene polymorphisms and lung cancer risk: An updated meta-analysis and review
Ping Zhan, Qin Wang, Qian Qian, Shu-Zhen Wei, Li-Ke Yu
Journal of Experimental & Clinical Cancer Research , 2011, DOI: 10.1186/1756-9966-30-99
Abstract: To assess this relationship more precisely, a meta-analysis and review were performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case-control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Ultimately, 64 studies, comprising 18,397 subjects from 49 case-control studies of the MspI genotype and 18,518 patients from 40 case-control studies of the exon 7 genotype, were included. A significantly elevated lung cancer risk was associated with 2 MspI genotype variants (for type C vs Type A: OR = 1.26, 95% CI = 1.12-1.42; for types B and C combined vs Type A: OR = 1.20, 95% CI = 1.13-1.28) in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians, lung SCC, lung AC and Male population, not in mixed population, lung SCLC and Female population. However, inconsistent results were observed for CYP1A1 exon7 in our meta-analysis, two variants of the exon 7 polymorphism were associated with a significantly higher risk for lung cancer (for Val/Val vs Ile/Ile: OR = 1.24, 95% CI = 1.09-1.42; for (Ile/Val +Val/Val) vs Ile/Ile: OR = 1.15, 95% CI = 1.07-1.24) in overall population. In the stratified analysis, a significant assocation was found in Asians, Caucasians, lung SCC and Female population, not in mixed population, lung AD, lung SCLC and Male population. Additionally, a significant association was found in smoker population and not found in non-smoker populations for CYP1A1 MspI and exon7 gene.This meta-analysis suggests that the MspI and exon 7 polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility and there is an interaction between two genotypes of CYP1A1 polymorphism and smoking, but these associations vary in different ethnic populations, histological types of lung caner and gender of case and control population.Lung cancer remains the most lethal cancer worldwide, despite improvements in di
Glutathione S-Transferase M1 Gene Polymorphism and Laryngeal Cancer Risk: A Meta-Analysis  [PDF]
Xin-Jiang Ying, Pin Dong, Bin Shen, Cheng-Zhi Xu, Hong-Ming Xu, Shu-Wei Zhao
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042826
Abstract: Background and Objectives Studies investigating the association between glutathione S-transferase M1 (GSTM1) gene polymorphism and laryngeal cancer risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible associations of GSTM1 gene polymorphism with laryngeal cancer risk. Methods The relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until May 2011 and selected on the basis of the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize association of GSTM1 polymorphism with laryngeal cancer susceptibility. Results Seventeen studies were included in the present meta-analysis (2,180 cases and 2,868 controls). The combined results based on all studies showed that GSTM1 null genotype was associated with increased laryngeal cancer risk (OR = 1.17, 95% CI = 1.04~1.31). When stratifying for race, GSTM1 null genotype exhibited increased laryngeal cancer risk in Caucasians (OR = 1.15, 95% CI = 1.01~1.31), while no significant association was detected in Asians (OR = 1.25, 95% CI = 0.80~1.96). In the subgroup analysis based on source of controls, significant associations were observed in the population-based studies (OR = 1.15, 95% CI = 1.01~1.31) yet not in the hospital-based studies (OR = 1.25, 95% CI = 0.93~1.67). Furthermore, in the subgroup analysis based on sample size, significant associations were also found in studies with at least 50 cases and 50 controls (OR = 1.15, 95% CI = 1.02~1.30) but not in studies with fewer than 50 cases or 50 controls (OR = 1.46, 95% CI = 0.87~2.46). Conclusions This meta-analysis supported that the GSTM1 gene polymorphism was associated with laryngeal cancer, particularly in Caucasians, and these associations varied in different subgroup, which indicated that population-based study with larger sample size was more appropriate in design of future study.
Polimorfismos en los genes de desintoxicación CYP1A1, CYP2E1, GSTT1 y GSTM1 en la susceptibilidad al cáncer gástrico
González,Auxiliadora; Ramírez,Vanessa; Cuenca,Patricia; Sierra,Rafaela;
Revista de Biología Tropical , 2004,
Abstract: 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 mspi 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). rev. biol. trop. 52(3): 591-600. epub 2004 dic 15.
CYP1A1 Polymorphisms and Risk of Prostate Cancer: A Meta-analysis  [cached]
Abjal Pasha Shaik,Kaiser Jamil,Prabhavathy Das
Urology Journal , 2009,
Abstract: Introduction: Two common polymorphisms in cytochrome P450; family 1, subfamily A, polypeptide 1 (CYP1A1); have been implicated as a risk factor of prostate cancer, but individual studies have been inconclusive or controversial. We reviewed studies on CYP1A1 polymorphisms in patients with prostate cancer. Materials and Methods: The strategy searching in the PubMed was based on combinations of prostate cancer, CYP1A1, CYP1A1 gene polymorphism, and genetic susceptibility. The last search update was May 2008. The retrieved articles and their bibliographies of were evaluated and reviewed independently by 2 experts. We shortlisted 19 studies, of which 14 on sporadic prostate cancer were analyzed. Overall, 2573 patients with prostate cancer and 2576 controls were analyzed. Results: The random effects odds ratio was 1.350 (95% confidence interval, 1.110 to 1.641; P = .003) for T/C polymorphism and 1.085 (95% confidence interval, 0.863 to 1.364; P = .49) for A/G polymorphism. The A/G polymorphism was not associated with increased risk of prostate cancer. However, the T/C polymorphism showed conflicting results in different studies, while overall, this polymorphism showed significant effects on the susceptibility to prostate cancer. There was no significant between-study heterogeneity for both polymorphisms with respect to distribution of alleles. Conclusion: This meta-analysis suggests that while the CYP1A1 T/C polymorphism is likely to considerably increase the risk of sporadic prostate cancer on a wide population basis, the A/G polymorphism may not influence this risk. However, the association of polymorphisms may be significant with respect to smoking history, diet habits, ethnicity, and race.
CYP1A1 MspI polymorphism and acute myeloid leukemia risk: meta-analyses based on 5018 subjects
Zhuo Wenlei,Zhang Liang,Wang Yan,Zhu Bo
Journal of Experimental & Clinical Cancer Research , 2012, DOI: 10.1186/1756-9966-31-62
Abstract: Background Evidence indicates that CYP1A1 MspI polymorphism might be a possible risk factor for several malignancies. A growing body of literature has been devoted to the association of CYP1A1 MspI polymorphism with acute myeloid leukemia (AML). However, the results remain conflicting. The aim of the present study was to derive a more precise estimation of the relationship. Methods Meta-analyses assessing the association of CYP1A1 MspI variation with AML were conducted and subgroup analyses on ethnicity and age groups were further performed. Eligible studies were identified for the period up to May 2012. Results A total of ten case–control studies including 1330 cases and 3688 controls were selected for analysis. The overall data failed to indicate a significant association of CYP1A1 MspI polymorphism with AML risk (C vs T: OR = 1.13; 95%CI = 0.87-1.48; CC vs TT: OR = 1.72; 95%CI = 0.99-3.01; CC + TC vs TT: OR = 1.16; 95%CI = 0.86-1.55). In subgroup analysis stratified by ethnicity, significant AML risk was shown among Asians (CC + TC vs TT: OR = 1.33; 95%CI = 1.09-1.62) but not Caucasians or mixed races. In subgroup analysis regarding age groups, no associations were observed in either the childhood AML or the adult AML subgroups. Conclusion The results of the present study suggested that CYP1A1 MspI polymorphism might be a risk factor for AML among Asians. Further investigations are needed to confirm the conclusions.
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