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Kneiber D, Kowalski EH, Amber KT. The Immunogenetics of Autoimmune Blistering Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1367:173-212. [DOI: 10.1007/978-3-030-92616-8_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
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Rehman MYA, Taqi MM, Hussain I, Nasir J, Rizvi SHH, Syed JH. Elevated exposure to polycyclic aromatic hydrocarbons (PAHs) may trigger cancers in Pakistan: an environmental, occupational, and genetic perspective. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:42405-42423. [PMID: 32875453 DOI: 10.1007/s11356-020-09088-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 04/27/2020] [Indexed: 05/22/2023]
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds which are emitted through incomplete combustion of organic materials, fossil fuels, consumption of processed meat, smoked food, and from various industrial activities. High molecular mass and mobility make PAHs widespread and lethal for human health. A cellular system in human detoxifies these toxicants through specialized enzymatic machinery called xenobiotic-metabolizing (CYP450) and phase-II (GSTs) enzymes (XMEs). These metabolizing enzymes include cytochromes P450 family (CYP1, CYP2), glutathione s-transferases, and ALDHs. Gene polymorphisms in XMEs encoding genes can compromise their metabolizing capacity to detoxify ingested carcinogens (PAHs etc.) that may lead to prolong and elevated exposure to ingested toxicants and may consequently lead to cancer. Moreover, PAHs can induce cancer through reprograming XMEs' gene functions by altering their epigenetic markers. This review article discusses possible interplay between individual's gene polymorphism in XMEs' genes, their altered epigenetic markers, and exposure to PAHs in cancer susceptibility in Pakistan.
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Affiliation(s)
- Muhammad Yasir Abdur Rehman
- Environmental Biology and Ecotoxicology Laboratory, Department of Environmental Sciences, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, PO, 45320, Pakistan
| | | | - Imran Hussain
- Department of Biotechnology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, PO, 45320, Pakistan
- Business Unit Environmental Resources and Technologies, Center for Energy, Austrian Institute of Technology (AIT), Vienna, Austria
| | - Jawad Nasir
- Earth Sciences Directorate, Pakistan Space and Upper Atmosphere Research Commission (SUPARCO), P.O. Box 8402, Karachi, 75270, Pakistan
| | - Syed Hussain Haider Rizvi
- Earth Sciences Directorate, Pakistan Space and Upper Atmosphere Research Commission (SUPARCO), P.O. Box 8402, Karachi, 75270, Pakistan
| | - Jabir Hussain Syed
- Department of Meteorology, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad, 45550, Pakistan.
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Yeh SH, Liu CL, Chang RC, Wu CC, Lin CH, Yang KD. Aging-dependent DNA hypermethylation and gene expression of GSTM1 involved in T cell differentiation. Oncotarget 2018; 8:48591-48602. [PMID: 28596482 PMCID: PMC5564710 DOI: 10.18632/oncotarget.18109] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Accepted: 05/10/2017] [Indexed: 02/04/2023] Open
Abstract
This study investigated whether aging was associated with epigenetic changes of DNA hypermethylation on immune gene expression and lymphocyte differentiation. We screened CG sites of methylation in blood leukocytes from different age populations, picked up genes with age-related increase of CG methylation content more than 15%, and validated immune related genes with CG hypermethylation involved in lymphocyte differentiation in the aged population. We found that 12 genes (EXHX1、 IL-10、 TSP50、 GSTM1、SLC5A5、SPI1、F2R、LMO2、PTPN6、FGFR2、MMP9、MET) were associated with promoter or exon one DNA hypermethylation in the aged group. Two immune related genes, GSTM1 and LMO2, were chosen to validate its aging-related CG hypermethylation in different leukocytes. We are the first to validate that GSTM1_P266 and LMO2_E128 CG methylation contents in T lymphocytes but not polymorphonuclear cells (PMNs) or mononuclear cells (MNCs) were significantly increased in the aged population. The GSTM1 mRNA expression in T lymphocytes but not PMNs or MNCs was inversely associated with the GSTM1 CG hypermethylation levels in the aged population studied. Further studies showed that lower GSTM1 CG methylation content led to the higher GSTM1 mRNA expression in T cells and knockdown of GSTM1 mRNA expression decreased type 1 T helper cell (Th1) differentiation in Jurkat T cells and normal adult CD4 T cells. The GSTM1_P266 hypermethylation in the aged population associated with lower GSTM1 mRNA expression was involved in Th1 differentiation, highlighting that modulation of aging-associated GSTM1 methylation may be able to enhance T helper cell immunity in the elders.
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Affiliation(s)
- Shu-Hui Yeh
- Graduate Institute of Long-Term Care, MacKay Medical College, New Taipei City, Taiwan
| | - Cheng-Ling Liu
- Department of Medical Research and Development, Show Chwan Memorial Hospital at Chang Bing, Changhua, Taiwan
| | - Ren-Chieh Chang
- Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Chiang Wu
- Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan
| | - Chia-Hsueh Lin
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
| | - Kuender D Yang
- Graduate Institute of Long-Term Care, MacKay Medical College, New Taipei City, Taiwan.,Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.,Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
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Akhtar N, Bansal JG. Risk factors of Lung Cancer in nonsmoker. Curr Probl Cancer 2017; 41:328-339. [PMID: 28823540 DOI: 10.1016/j.currproblcancer.2017.07.002] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 05/12/2017] [Accepted: 07/17/2017] [Indexed: 12/18/2022]
Abstract
Generally, the cause of lung cancer is attributed to tobacco smoking. But many of the new lung cancer cases have been reported in nonsmokers. Apart from smoking; air pollution, environmental exposure, mutations, and single-nucleotide polymorphisms are known to be associated with lung cancer. Improper diet, alcohol consumption, marijuana smoking, estrogen, infections with human papillomavirus (HPV), HIV, and Epstein-Barr virus are suggested to be linked with lung cancer but clear evidences to ascertain their relation is not available. This article provides a comprehensive review of various risk factors and the underlying molecular mechanisms responsible for increasing the incidence of lung cancer. The pathologic, histologic, and genetic differences exist with lung cancer among smokers and nonsmokers. A better understanding of the risk factors, differences in pathology and molecular features of lung cancer in smokers and nonsmokers and the mode of action of various carcinogens will facilitate the prevention and management of lung cancer.
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Affiliation(s)
- Nahid Akhtar
- Department of Bioengineering and Biosciences, Lovely Professional University (LPU), Phagwara, Punjab, India
| | - Jeena Gupta Bansal
- Department of Bioengineering and Biosciences, Lovely Professional University (LPU), Phagwara, Punjab, India.
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Zhang F, Wu X, Niu J, Kang X, Cheng L, Lv Y, Wu M. GSTM1 polymorphism is related to risks of nasopharyngeal cancer and laryngeal cancer: a meta-analysis. Onco Targets Ther 2017; 10:1433-1440. [PMID: 28331336 PMCID: PMC5348073 DOI: 10.2147/ott.s131611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Accumulating data have reported that GSTM1 polymorphism may be related to nasopharyngeal cancer (NPC) and laryngeal cancer (LC). This meta-analysis was performed to investigate the relationship between GSTM1 polymorphism and risks of NPC and LC. Methods Pubmed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched for potential articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship of GSTM1 polymorphism with the risks of NPC and LC. I2>50% or P<0.05 indicates significant heterogeneity. When heterogeneity existed, the random-effects model was used to pool data, otherwise, the fixed-effects model was adopted. Publication bias was detected by Begg’s funnel plot and Egger’s regression. Quality of each study was evaluated by Newcastle-Ottawa Scale. Results Thirty-two eligible articles were included. Pooled outcome suggested the significant relationship of GSTM1 null genotype with increased risk of LC (OR =1.28, 95% CI =1.05–1.54). Compared with hospital-based (HB) population, GSTM1 null genotype was also related to increased risk of LC (OR =1.38, 95% CI =1.06–1.80). Positive relationship of GSTM1 null genotype with enhanced risk of NPC was observed (OR =1.43, 95% CI =1.26–1.63). A similar trend was also observed in the subgroup analysis by source of control (population-based [PB]: OR =1.39, 95% CI =1.18–1.63; HB: OR =1.52, 95% CI =1.22–1.89). Conclusion GSTM1 null genotype is related to increased risk of NPC and LC.
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Affiliation(s)
- Fengying Zhang
- Otorhinolaryngological Department, Wei Fang Traditional Chinese Hospital, Weifang, Shandong Province, China
| | - Xijiang Wu
- Otorhinolaryngological Department, Shouguang Peoples Hospital, Shouguang, Shandong Province, China
| | - Jinming Niu
- Otorhinolaryngological Department, Wei Fang Traditional Chinese Hospital, Weifang, Shandong Province, China
| | - Xiufeng Kang
- Medical insurance office, Shouguang Peoples Hospital, Shouguang, Shandong Province, China
| | - Liya Cheng
- Otorhinolaryngological Department, Wei Fang Traditional Chinese Hospital, Weifang, Shandong Province, China
| | - Yanchun Lv
- Otorhinolaryngological Department, Wei Fang Traditional Chinese Hospital, Weifang, Shandong Province, China
| | - Meimei Wu
- Otorhinolaryngological Department, Wei Fang Traditional Chinese Hospital, Weifang, Shandong Province, China
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Zhang J, Zhu X, Li Y, Zhu L, Li S, Zheng G, Ren Q, Xiao Y, Feng F. Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2016; 13:ijerph13080776. [PMID: 27490558 PMCID: PMC4997462 DOI: 10.3390/ijerph13080776] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Revised: 07/18/2016] [Accepted: 07/27/2016] [Indexed: 12/21/2022]
Abstract
This study investigated the role of CpG island methylation of the CYP2E1 and CYP2D6 genes in liver injury induced by anti-TB drugs from an epigenetic perspective in a Chinese cohort. A 1:1 matched nested case-control study design was applied. Pulmonary tuberculosis (TB) patients, who underwent standard anti-TB therapy and developed liver injury were defined as cases, while those who did not develop liver injury were defined as control. The two groups were matched in terms of sex, treatment regimen, and age. In 114 pairs of cases, CpG island methylation levels of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of anti-TB drug-induced liver injury (ADLI), with odds ratio (OR) values of 2.429 and 3.500, respectively (p < 0.01). Moreover, through multivariate logistic regression analysis, CpG island methylation of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of ADLI, with adjusted OR values of 4.390 (95% confidence interval (CI): 1.982–9.724) and 9.193 (95% CI: 3.624–25.888), respectively (p < 0.001). These results suggest that aberrantly elevated methylation of CpG islands of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA may increase the risk of ADLI in Chinese TB patients.
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Affiliation(s)
- Jinling Zhang
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
| | - Xuebin Zhu
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
| | - Yuhong Li
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
| | - Lingyan Zhu
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
| | - Shiming Li
- Department of Clinical Laboratories, Tangshan Tuberculosis Hospital, Tangshan 063000, China.
| | - Guoying Zheng
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
| | - Qi Ren
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
| | - Yonghong Xiao
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
| | - Fumin Feng
- Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China.
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Yang H, Yang S, Liu J, Shao F, Wang H, Wang Y. The association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population: evidence from an updated meta-analysis. Sci Rep 2015; 5:9392. [PMID: 25797617 PMCID: PMC4369748 DOI: 10.1038/srep09392] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Accepted: 03/03/2015] [Indexed: 11/12/2022] Open
Abstract
Previous studies have reported the association of glutathione S-transferase M1 (GSTM1) deletion polymorphism with genetic susceptibility of lung cancer in Chinese population. However, the results remained controversial. The aim of this study was to clarify the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population. Systematic searches were performed through the search engines of Medline/Pubmed, Web of Science, EMBASE, CNKI and Wanfang Medical Online. The pooled effects were calculated by STATA 10.0 software package and Review Manager 5.0.24. Overall, we observed an association of GSTM1 deletion polymorphism with increased lung cancer risk in Chinese population (odds ratio (OR) = 1.46, 95% confidence interval (95%CI): 1.32-1.66 for null genotype vs. present genotype) based on 53 studies including 7,833 cases and 10,353 controls. We also observed an increased risk of GSTM1 null genotype for lung cancer in stratified analyses by source of control, smoking status and histological type. The findings suggest that GSTM1 deletion polymorphism may contribute to lung cancer risk in Chinese population. Further, well-designed studies with larger sample sizes are required to verify the results.
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Affiliation(s)
- Haiyan Yang
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Siyu Yang
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Jing Liu
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Fuye Shao
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Haiyu Wang
- Department of Toxicology, Henan Center for Disease Control and Prevention, Zhengzhou 450016, China
| | - Yadong Wang
- Department of Toxicology, Henan Center for Disease Control and Prevention, Zhengzhou 450016, China
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Liu X, Li Z, Zhang Z, Zhang W, Li W, Xiao Z, Liu H, Jiao H, Wang Y, Li G. Meta-analysis of GSTM1 null genotype and lung cancer risk in Asians. Med Sci Monit 2014; 20:1239-45. [PMID: 25033877 PMCID: PMC4111653 DOI: 10.12659/msm.890490] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Several molecular epidemiological studies have been conducted to examine the association between glutathione S-transferase M 1 (GSTM1) null genotype and lung cancer in Asians; however, the conclusions remained controversial. We therefore performed an extensive meta-analysis on 31 published case-control studies with a total of 5347 lung cancer cases and 6072 controls. MATERIAL/METHODS PubMed and EMBASE were searched to identify case-control studies investigating the associations of GSTM1 null genotype with risk of lung cancer in Asians. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between lung cancer risk and polymorphism of GSTM1. RESULTS GSTM1 null genotype was significantly associated with lung cancer risk (OR=1.43; 95% CI, 1.30-1.58). This result remained statistically significant when the adjusted ORs were combined (OR=1.38; 95% CI, 1.23-1.54). In the subgroup analysis by sex, there were significant associations in women and men. When stratifying for histology, this genotype showed increased adenocarcinoma risk and squamous cell carcinoma risk. In the subgroup analysis stratified by smoking status, lung cancer risk was increased in both smokers and non-smokers. CONCLUSIONS This study suggests that GSTM1 null genotype is a risk factor for lung cancer in Asians.
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Affiliation(s)
- Xiaomin Liu
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Zhijuan Li
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Zhiye Zhang
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Weimin Zhang
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Wei Li
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Zhongyue Xiao
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Huazhuan Liu
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Hongduo Jiao
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Yi Wang
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
| | - Guoguo Li
- Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China (mainland)
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Liu K, Lin X, Zhou Q, Ma T, Han L, Mao G, Chen J, Yue X, Wang H, Zhang L, Jin G, Jiang J, Zhao J, Zou B. The associations between two vital GSTs genetic polymorphisms and lung cancer risk in the Chinese population: evidence from 71 studies. PLoS One 2014; 9:e102372. [PMID: 25036724 PMCID: PMC4103841 DOI: 10.1371/journal.pone.0102372] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Accepted: 06/17/2014] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population. METHODS Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests. RESULTS 71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004). CONCLUSIONS An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies.
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Affiliation(s)
- Kui Liu
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
- Department of Science Research and Information Management,Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People's Republic of China
| | - Xialu Lin
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
| | - Qi Zhou
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
| | - Ting Ma
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
- Department of Science Research and Information Management,Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People's Republic of China
| | - Liyuan Han
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
| | - Guochuan Mao
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
- Municipal Center for Disease Prevention and Control of Ningbo City, Ningbo, Zhejiang Province, People's Republic of China
| | - Jian Chen
- Department of Epidemiology and Health Statistic, Anhui Medical University, Hefei, Anhui Province, People's Republic of China
| | - Xia Yue
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
| | - Huiqin Wang
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
| | - Lu Zhang
- School of Health Management, Anhui Medical University, Hefei, Anhui Province, People's Republic of China
| | - Guixiu Jin
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
| | - Jianmin Jiang
- Department of Science Research and Information Management,Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People's Republic of China
| | - Jinshun Zhao
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
| | - Baobo Zou
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China
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GSTM1 polymorphism and lung cancer risk among East Asian populations: a meta-analysis. Tumour Biol 2014; 35:6493-500. [PMID: 24682953 DOI: 10.1007/s13277-014-1832-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Accepted: 03/06/2014] [Indexed: 10/25/2022] Open
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Fortes C, Mastroeni S, Boffetta P, Antonelli G, Pilla MA, Bottà G, Anzidei P, Venanzetti F. The protective effect of coffee consumption on cutaneous melanoma risk and the role of GSTM1 and GSTT1 polymorphisms. Cancer Causes Control 2013; 24:1779-87. [PMID: 23860951 DOI: 10.1007/s10552-013-0255-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 06/24/2013] [Indexed: 01/12/2023]
Abstract
PURPOSES The authors examined the association between coffee consumption and cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms. METHODS A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 controls. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected for all subjects. Within the study, individual patterns at two polymorphic genes (GSTM1 and GSTT1) belonging to glutathione S-transferases family were investigated in 188 cases of cutaneous melanoma and 152 controls. Logistic regression was the method used to estimate odds ratio and 95 % confidence intervals. RESULTS High frequency of coffee drinking (>once daily), compared with low-frequency consumption of coffee (≤7 times weekly) was associated with a protective effect for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age, education, hair colour, common nevi, skin phototype, and sunburn episodes in childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of coffee was extremely high for subjects with both GSTM1 and GSTT1 null polymorphisms (OR 0.01; 95 % CI 0.0003-0.54). CONCLUSIONS Our results show a protective effect of coffee consumption for cutaneous melanoma, in particular for those with homozygous deletion for GSTM1 and GSTT1.
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Affiliation(s)
- Cristina Fortes
- Clinical Epidemiology Unit, Istituto Dermopatico dell'Immacolata, IDI-IRCSS, Via dei Monti di Creta, 104, 00167, Rome, Italy,
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CYP2D6 T188C variant is associated with lung cancer risk in the Chinese population. Tumour Biol 2013; 34:2189-93. [DOI: 10.1007/s13277-013-0755-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 03/18/2013] [Indexed: 10/27/2022] Open
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Marshall AL, Christiani DC. Genetic susceptibility to lung cancer--light at the end of the tunnel? Carcinogenesis 2013; 34:487-502. [PMID: 23349013 PMCID: PMC3581605 DOI: 10.1093/carcin/bgt016] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2012] [Revised: 12/30/2012] [Accepted: 01/17/2013] [Indexed: 01/10/2023] Open
Abstract
Lung cancer is one of the most common and deadliest cancers in the world. The major socio-environmental risk factor involved in the development of lung cancer is cigarette smoking. Additionally, there are multiple genetic factors, which may also play a role in lung cancer risk. Early work focused on the presence of relatively prevalent but low-penetrance alterations in candidate genes leading to increased risk of lung cancer. Development of new technologies such as genomic profiling and genome-wide association studies has been helpful in the detection of new genetic variants likely involved in lung cancer risk. In this review, we discuss the role of multiple genetic variants and review their putative role in the risk of lung cancer. Identifying genetic biomarkers and patterns of genetic risk may be useful in the earlier detection and treatment of lung cancer patients.
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Affiliation(s)
| | - David C. Christiani
- Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
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Zhang Y, Liu C. The interaction between smoking and GSTM1 variant on lung cancer in the Chinese population. Tumour Biol 2013; 34:395-401. [PMID: 23090633 DOI: 10.1007/s13277-012-0562-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Accepted: 10/12/2012] [Indexed: 12/22/2022] Open
Abstract
Smoking and the deletion of GSTM1 variant are two risk factors of lung cancer. This meta-analysis was performed to examine the GSTM1-smoking interaction on lung cancer in the Chinese population. PubMed, Web of Science, and other Chinese databases were searched to include all the related studies. The number of subjects with two GSTM1 genotypes across different smoking status was extracted. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated using fixed- or random-effect model. A total of 4,345 cases and 5,031 controls from 30 studies were included in the meta-analysis. Compared with nonsmokers having power GSTM1, the pooled ORs with 95 % CIs for lung cancer in smokers with power GSTM1, in nonsmokers with null GSTM1, and in smokers with null GSTM1 were 2.24 (1.82-2.76), 1.48 (1.23-1.79), and 4.18 (3.38-5.16), respectively. This meta-analysis showed that there was an interaction between the GSTM1 and smoking on the risk of lung cancer in the Chinese. Further studies are needed to examine the interactions between other environmental factors and GSTM1 on the risk of lung cancer.
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Affiliation(s)
- Yanan Zhang
- Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, 200032, China
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Shukla RK, Tilak AR, Kumar C, Kant S, Kumar A, Mittal B, Bhattacharya S. Associations of CYP1A1, GSTM1 and GSTT1 polymorphisms with lung cancer susceptibility in a Northern Indian population. Asian Pac J Cancer Prev 2013; 14:3345-3349. [PMID: 23803127 DOI: 10.7314/apjcp.2013.14.5.3345] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation in lung cancer incidence with ethnicity. MATERIALS AND METHODS We conducted a case-control study of 218 northern Indian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lung cancer in our population. RESULTS We observed a significant difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=1.87, 95%CI: 1.25-2.80-0.73, P=0.002). However, GSTM1 null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). CONCLUSIONS Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.
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Affiliation(s)
- R K Shukla
- King George's Medical University, Lucknow, India
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Assessment of cumulative evidence for the association between glutathione S-transferase polymorphisms and lung cancer: application of the Venice interim guidelines. Pharmacogenet Genomics 2011; 20:586-97. [PMID: 20729793 DOI: 10.1097/fpc.0b013e32833c3892] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE There is an overwhelming abundance of genetic association studies available in the literature, which can often be collectively difficult to interpret. To address this issue, the Venice interim guidelines were established for determining the credibility of the cumulative evidence. The objective of this report is to evaluate the literature on the association of common glutathione S-transferase (GST) variants (GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphism) and lung cancer, and to assess the credibility of the associations using the newly proposed cumulative evidence guidelines. METHODS Information from the literature was enriched with an updated meta-analysis and a pooled analysis using data from the Genetic Susceptibility to Environmental Carcinogens database. RESULTS There was a significant association between GSTM1 null and lung cancer for the meta-analysis (meta odds ratio=1.17, 95% confidence interval: 1.10-1.25) and pooled analysis (adjusted odds ratio=1.10, 95% confidence interval: 1.04-1.16), although substantial heterogeneity was present. No overall association between lung cancer and GSTT1 null or GSTP1 Ile105Val was found. When the Venice criteria was applied, cumulative evidence for all associations were considered 'weak', with the exception of East Asian carriers of the G allele of GSTP1 Ile105Val, which was graded as 'moderate' evidence. CONCLUSION Despite the large amounts of studies, and several statistically significant summary estimates produced by meta-analyses, the application of the Venice criteria suggests extensive heterogeneity and susceptibility to bias for the studies on association of common genetic polymorphisms, such as with GST variants and lung cancer.
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Copy number variants of GSTM1 and GSTT1 in relation to lung cancer risk in a prospective cohort study. Ann Epidemiol 2009; 19:546-52. [PMID: 19394866 DOI: 10.1016/j.annepidem.2009.03.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2008] [Revised: 02/26/2009] [Accepted: 03/01/2009] [Indexed: 01/10/2023]
Abstract
PURPOSE Previous studies did not discriminate wild-type from hemizygous genotypes of GSTM1 and GSTT1. In this study, we investigated wild-type, hemizygous deletion, and homozygous deletion genotypes of GSTM1 and GSTT1 and lung cancer risk. METHODS We conducted a nested case-control study of 143 primary incident lung cancer cases matched to 447 cancer-free controls. Genotyping was carried out using a real-time polymerase chain reaction (PCR)-based assay. Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS Compared to GSTM1 wild-type carriers, the relative odds of lung cancer increased from 1.49 (95% CI=0.66-3.40) to 1.80 (95% CI=0.81-4.02) for the hemizygous and homozygous deletion genotypes, respectively (p-trend=0.13). The strongest associations were seen among those who smoked less than one pack per day and had greater than or equal to one deletion variant of GSTM1 (OR=3.25; 95% CI=0.93-11.34; p-trend=0.07) whereas the reverse was observed for smokers who smoked greater than or equal to one pack per day (OR=0.80; 95% CI=0.24-2.67; p-interaction=0.08). No clear associations were observed for GSTT1 genotypes. CONCLUSIONS Risk of lung cancer increased as the number of deletion variants increased for GSTM1, although the associations were nonsignificant. Discriminating between the wild-type, hemizygous, and homozygous deletion GSTM1 genotypes permitted a more precise characterization of the associations between GSTM1 deletion variants and lung cancer.
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Ginsberg G, Smolenski S, Hattis D, Guyton KZ, Johns DO, Sonawane B. Genetic Polymorphism in Glutathione Transferases (GST): Population distribution of GSTM1, T1, and P1 conjugating activity. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2009; 12:389-439. [PMID: 20183528 DOI: 10.1080/10937400903158375] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Glutathione transferases (GST) catalyze the conjugation of glutathione (GSH) with electrophiles, many of which may otherwise interact with protein or DNA. In select cases such as halogenated solvents, GST-mediated conjugation may lead to a more toxic or mutagenic metabolite. Polymorphisms that exert substantial effects on GST function were noted in human populations for several isozymes. This analysis focuses on three well-characterized isozymes, GSTM1, T1, and P1, in which polymorphisms were extensively studied with respect to DNA adducts and cancer in molecular epidemiologic studies. The current review and analysis focused upon how polymorphisms in these GST contributed to population variability in GST function. The first step in developing this review was to characterize the influence of genotype on phenotype (enzyme function) and the frequency of the polymorphisms across major population groups for all three GST. This information was then incorporated into Monte Carlo simulations to develop population distributions of enzyme function. These simulations were run separately for GSTM1, T1, and P1, and also for the combination of these isozymes, to assess the possibility of overlapping substrate specificity. Monte Carlo simulations indicated large interindividual variability for GSTM1 and T1 due to the presence of the null (zero activity) genotype, which is common in all populations studied. Even for GSTM1 or T1 non-null individuals, there was considerable interindividual variability with a bimodal distribution of enzyme activity evident. GSTP1 polymorphisms are associated with somewhat less variability due to the absence of null genotypes. However, in all cases simulated, the estimated variability is sufficiently large to warrant consideration of GST function distributions in assessments involving GST-mediated activation or detoxification of xenobiotics. Ideally, such assessments would involve physiologically based toxicokinetic (PBTK) modeling to assess population variability in internal dose.
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Affiliation(s)
- Gary Ginsberg
- Connecticut Department of Public Health, Hartford 06134, USA.
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Sobti RC, Sharma S, Joshi A, Jindal SK, Janmeja A. CYP1A1andCYP2D6polymorphism and risk of lung cancer in a North Indian population. Biomarkers 2008; 8:415-28. [PMID: 14602525 DOI: 10.1080/13547500310001619860] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
This case-control study was conducted to examine the association between the CYP1A1 and CYP2D6 genotypes and lung cancer risk among North Indians. The estimated relative risk for lung cancer associated with the CYP1A1 Val/Val allele was 2.68, and was four-fold when cases with small cell lung cancer (SCLC) were considered alone. With regard to the metabolism of debrisoquine, no poor metabolizers were found amongst the subjects. The odds ratio of risk with the heterozygous extensive metabolizer (HEM) genotype was 1.5. However, in the presence of at least a single copy of the variant CYP1A1 MspI allele and the CYP2D6 HEM genotype, the risk was two-fold for squamous cell carcinoma (SQCC). When the CYP1A1 Val/Val and CYP2D6 HEM genotypes were taken together, the risk for SCLC was four-fold. Stratified analysis indicated an interaction between bidi smoking and variant CYP1A1 genotypes on the risk for SQCC and SCLC. Heavy smokers (Brinkman index>400) with Val/Val genotypes were at a very high risk of developing lung cancer (odds ratio 29.30, 95% confidence interval 2.42-355, p=0.008). Heavy smokers with CYP1A1 MspI (CYP1A1*1/2A or CYP1A1*2A/*2A) genotype had a seven-fold risk for SCLC compared with non-smokers. This study is the first to be carried out on a North Indian population, and, although small, suggests that CYP1A1 and CYP2D6 polymorphisms might have a role in determining the risk for lung cancer and should be investigated further.
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Affiliation(s)
- R C Sobti
- Department of Biotechnology, Panjab University, Chandigarh, India.
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Genetic polymorphisms of metabolic enzymes CYP1A1, CYP2D6, GSTM1 and GSTT1 and leukemia susceptibility. Eur J Cancer Prev 2008; 17:251-8. [PMID: 18414197 DOI: 10.1097/cej.0b013e3282b72093] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The genetic polymorphisms of biotransformation phase I enzymes, cytochrome P450 (CYP1A1 and CYP2D6), and phase II enzymes, glutathione S-transferase (GSTM1 and GSTT1), were analyzed in 204 healthy persons and 348 leukemia patients, who suffered from also acute lymphoblastic leukemia (ALL), acute nonlymphoblastic leukemia (ANLL) chronic myelogenous leukemia (CML), from the Han ethnic group in Changsha City of Hunan Province of China. Our results showed that the frequencies of polymorphisms of CYP1A1, CYP2D6 and GSTT1 among the groups including acute lymphoblastic leukemia, ANLL, chronic myelogenous leukemia and healthy control have no significant differences. The variation of GSTM1-null genotype alone correlated with the development of ANLL. The combined genotypes of GSTM1-null with GSTT1-null, or GSTM1-null with CYP1A1 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant and CYP2D6 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant, CYP2D6 heterozygous mutant and GSTT1-null were found in individuals with high risk of ANLL. All these findings suggest that GSTM1-null genotype alone or in coordination with the relevant genotypes of other metabolic enzymes might be susceptibility factors in the etiology of ANLL.
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Carlsten C, Sagoo GS, Frodsham AJ, Burke W, Higgins JPT. Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis. Am J Epidemiol 2008; 167:759-74. [PMID: 18270371 DOI: 10.1093/aje/kwm383] [Citation(s) in RCA: 132] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Multiple genes have been studied for potential associations with lung cancer. The gene most frequently associated with increased risk has been glutathione S-transferase M1 (GSTM1). The glutathione S-transferase enzyme family is known to catalyze detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. In this review, the authors summarize the available evidence associating lung cancer with the GSTM1 gene. They describe results from an updated meta-analysis of 98 published genetic association studies investigating the relation between the GSTM1 null variant and lung cancer risk including 19,638 lung cancer cases and 25,266 controls (counting cases and controls in each study only once). All studies considered, the GSTM1 null variant was associated with an increased risk of lung cancer (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14, 1.30), but no increase in risk was seen (OR = 1.01, 95% CI: 0.91, 1.12) when only the five largest studies (>500 cases each) were considered. Furthermore, while GSTM1 null status conferred a significantly increased risk of lung cancer to East Asians (OR = 1.38, 95% CI: 1.24, 1.55), such a genotype did not confer increased risk to Caucasians. More data regarding the predictive value of GSTM1 genetic testing are needed before population-based testing may be reasonably considered.
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Affiliation(s)
- C Carlsten
- Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
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Ye Z, Song H, Higgins JPT, Pharoah P, Danesh J. Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies. PLoS Med 2006; 3:e91. [PMID: 16509765 PMCID: PMC1391981 DOI: 10.1371/journal.pmed.0030091] [Citation(s) in RCA: 110] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2005] [Accepted: 12/12/2005] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Glutathione S-transferases (GSTs) are known to abolish or reduce the activities of intracellular enzymes that help detoxify environmental carcinogens, such as those found in tobacco smoke. It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results. METHODS AND FINDINGS Literature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of five GST polymorphisms (GSTM1 null, GSTT1 null, I105V, and A114V polymorphisms in the GSTP1 genes, and GSTM3 intron 6 polymorphism) available before August, 2005, with investigation of potential sources of heterogeneity. Included in the present meta-analysis were 130 studies, involving a total of 23,452 lung cancer cases and 30,397 controls. In a combined analysis, the relative risks for lung cancer of the GSTM1 null and GSTT1 null polymorphisms were 1.18 (95% confidence interval [CI]: 1.14-1.23) and 1.09 (95% CI: 1.02-1.16), respectively, but in the larger studies they were only 1.04 (95% CI: 0.95-1.14) and 0.99 (95% CI: 0.86-1.11), respectively. In addition to size of study, ethnic background was a significant source of heterogeneity among studies of the GSTM1 null genotype, with possibly weaker associations in studies of individuals of European continental ancestry. Combined analyses of studies of the 105V, 114V, and GSTM3*B variants showed no significant overall associations with lung cancer, yielding per-allele relative risks of 1.04 (95% CI: 0.99-1.09), 1.15 (95% CI: 0.95-1.39), and 1.05 (95% CI: 0.89-1.23), respectively. CONCLUSIONS The risk of lung cancer is not strongly associated with the I105V and A114V polymorphisms in the GSTP1 gene or with GSTM3 intron 6 polymorphism. Given the non-significant associations in the larger studies, the relevance of the weakly positive overall associations with the GSTM1 null and the GSTT1 null polymorphisms is uncertain. As lung cancer has important environmental causes, understanding any genetic contribution to it in general populations will require the conduct of particularly large and comprehensive studies.
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Affiliation(s)
- Zheng Ye
- Department of Public Health and Primary Care, University of Cambridge, Strangeways Site, Cambridge, United Kingdom.
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Chan EC, Lam SY, Fu KH, Kwong YL. Polymorphisms of the GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes in Chinese patients with non-small cell lung cancers: relationship with aberrant promoter methylation of the CDKN2A and RARB genes. ACTA ACUST UNITED AC 2005; 162:10-20. [PMID: 16157195 DOI: 10.1016/j.cancergencyto.2005.03.008] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2004] [Revised: 03/02/2005] [Accepted: 03/08/2005] [Indexed: 01/29/2023]
Abstract
An association between functional polymorphisms of genes resulting in decreased detoxification of carcinogens or DNA repair and aberrant promoter methylation is an attractive hypothesis in lung carcinogenesis. The genotypes at polymorphic sites of the glutathione S-transferase (GST) M1 (null/wildtype) and P1 (nucleotide 2627 A/G), myeloperoxidase (MPO) (nucleotide -463 G/A), X-ray repair cross-complementing group 1 (XRCC1) (nucleotides 26304 C/T; 28152 G/A), and NADPH quinine oxidoreductase (NQO1) (nucleotide 609 C/T) genes in 75 Chinese patients with non-small cell lung cancer (NSCLC) were characterized with polymerase chain reaction-restriction fragment length polymorphism. Results were correlated with aberrant methylation of the CDKN2A (alias p16(INK4A)), retinoic acid receptor beta (RARB), methylguanine-DNA methyltransferase (MGMT), and death-associated-protein (DAP) kinase genes in the tumors. In comparison with an age-matched control, none of the polymorphisms were associated with increased lung cancer risks. In male patients, however, the MPO -463 GG homozygous state was associated with CDKN2A (alias p16(INK4A)) methylation (odds ratio OR=3.63, 95% confidence interval CI=1.26-10.51), and the XRCC1 26304 T allele in the heterozygous/homozygous state was associated with methylation of CDKN2A (OR=6.13, 95% CI=1.55-24.16) and RARB (OR=7.67, 95% CI=1.62-36.18). In female patients, the GSTP1 G allele in the heterozygous/homozygous state was associated with RARB methylation (OR=18.0, 95% CI=0.76-427.29). These results showed that functional deficiencies in metabolic pathways that protect cells from carcinogen induced DNA damage might be linked to aberrant promoter methylation of the CDKN2A and RARB genes during lung carcinogenesis.
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Affiliation(s)
- Eunice C Chan
- University Department of Medicine, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China
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Sreeja L, Syamala V, Hariharan S, Madhavan J, Devan SC, Ankathil R. Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population. J Hum Genet 2005; 50:618-27. [PMID: 16228113 DOI: 10.1007/s10038-005-0303-3] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2005] [Accepted: 08/16/2005] [Indexed: 10/25/2022]
Abstract
Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. As the incidence of lung cancer is known to differ according to ethnicity, we have conducted a case-control study of 146 South Indian lung cancer patients along with 146 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of lung cancer in our population. The current weight of evidence from our study indicated that the frequency of CYP1A1 MspI homozygous variant alleles was significantly higher in cases (OR = 3.178). We observed a considerable difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR = 2.472, 95% CI: 1.191-5.094, P = 0.014). There was no relative risk in GSTM1 null genotype when analysed singly (P = 0.453). Considering genotype combinations, risk of lung cancer increased remarkably significantly in individuals having one variant allele of CYP1A1, GSTM1, or GSTT1, suggesting gene-gene interactions. Rare genotypic combinations (such as CYP1A1 wild GSTM1 or GSTT1 either null; CYP1A1 variant both GSTM1 and GSTT1 present; CYP1A1 variant GSTM1 or GSTT1 either null), were at higher risk compared to the reference group. Moreover, patients who had smoked <20 pack years and harboured the CYP1A1 variant allele or the GSTT1 null genotype also had a significant risk of lung cancer. Hence our study-the first to analyse a South Indian population-suggests the importance of combined CYP1A1, GSTM1 and GSTT1 polymorphisms in the development of smoking-induced lung cancer.
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Affiliation(s)
- Leelakumari Sreeja
- Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India
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Abstract
The mortality rate of lung cancer in Asian women has increased significantly in the past few decades. Environmental factors include tobacco smoke (active and environmental), other indoor pollutions (cooking oil vapours, coal burning, fungus spores), diet, and infections. Active tobacco smoking is not the major factor. The relative risk of lung cancer among non-smoking women ever exposed to environmental smoke from their husbands was 1.20 from a meta-analysis. Cooking oil vapours associated with high temperature wok cooking and indoor coal burning for heating and cooking in unvented homes, particularly in rural areas, are risk factors for Chinese women. Chronic benign respiratory diseases due to the fungus Microsporum canis probably accounts for the high incidence of lung cancer in northern Thai women at Sarapee. Diets rich in fruits, leafy green vegetables, and vitamin A are protective, while cured meat (Chinese sausage, pressed duck and cured pork), deep-fried cooking, and chili increased the risk. Tuberculosis is associated with lung cancer. Also, a Taiwanese study showed that the odds ratio of papillomavirus (HPV) 16/18 infection in non-smoking female lung cancer patients was 10.1, strongly suggesting a causative role. Genetic factors have also been studied in Chinese women, including human leucocyte antigens, K-ras oncogene activation, p53 mutation, polymorphisms of phase I activating enzymes (cytochrome P450, N-acetyltransferase slow acetylator status), and phase II detoxifying enzymes (glutathione-S-transferases, N-acetyltransferase rapid acetylator status). New molecular screening technology would facilitate identification of molecular targets for future studies. The interaction between environmental and genetic factors should also be further elucidated.
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Affiliation(s)
- Wah Kit Lam
- Department of Medicine, the University of Hong Kong, Hong Kong.
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Chan-Yeung M, Tan-Un KC, Ip MSM, Tsang KWT, Ho SP, Ho JCM, Chan H, Lam WK. Lung cancer susceptibility and polymorphisms of glutathione-S-transferase genes in Hong Kong. Lung Cancer 2004; 45:155-60. [PMID: 15246186 DOI: 10.1016/j.lungcan.2004.01.016] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2003] [Revised: 01/13/2004] [Accepted: 01/15/2004] [Indexed: 12/01/2022]
Abstract
OBJECTIVE To study the potential role of genetic polymorphisms of glutathione-S-transferases GSTM1, GSTT1 and GSTP1 in susceptibility to lung cancer in Hong Kong Chinese. METHODS 229 consecutive incident patients with a histological diagnosis of lung cancer from a regional hospital and 197 healthy population-based controls were recruited for this study between July 1999 and June 2001. Genetic polymorphisms of GSTT1 and GSTM1 were determined using PCR-based technique. RESULTS The frequencies of GSTT1 and GSTM1 null genotypes were 51.8 and 59.4% in healthy controls and 63 and 54.7%, respectively, in lung cancer patients. GSTP1 Val105/Val105 genotype was found in only 1% of healthy controls. The risk for lung cancer with GSTT1 null genotype was significantly higher, adjusted odds ratio (OR) 1.69, 95% confidence interval (CI) 1.12-2.56, compared with those with the GSTT1 genotype; the increase in risk was found only in non-smokers. GSTM1 null genotype, combined GSTT1 and GSTM1 null genotype and GSTP1 Val105/Val105 genotype did not confer any increase risk for lung cancer. CONCLUSION GSTT1 null genotype is associated with an increased risk for lung cancer in non-smoking Chinese in Hong Kong.
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Affiliation(s)
- Moira Chan-Yeung
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, SAR, PR China.
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Abstract
AIM: Over 90% of drugs are metabolized by the cytochrome P-450 (CYP) family of liver isoenzymes. The most important enzymes are CYP1A2, 3A4, 2C9/19, 2D6 and 2E1. Although CYP2D6 accounts for < 2% of the total CYP liver enzyme content, it mediates metabolism in almost 25% of drugs. In order to study its enzymatic activity for drug metabolism, its cDNA was cloned and a HepG2 cell line stably expressing CYP2D6 was established.
METHODS: Human CYP2D6 cDNA was amplified with reverse transcription-polymerase chain reaction (RT-PCR) from total RNA extracted from human liver tissue and cloned into pGEM-T vector. cDNA segment was identified by DNA sequencing and subcloned into a mammalian expression vector pREP9. A cell line was established by transfecting the recombinant plasmid of pREP9-CYP2D6 to hepatoma HepG2 cells. Expression of mRNA was validated by RT-PCR. Enzyme activity of catalyzing dextromethorphan O-demethylation in postmitochondrial supernant (S9) fraction of the cells was determined by high performance liquid chromatography (HPLC).
RESULTS: The cloned cDNA had 4 base differences, e.g. 100 C→T, 336 T→C, 408 C→G and 1 457 G→C, which resulted in P34S, and S486T amino acid substitutions, and two samesense mutations were 112 F and 136 V compared with that reported by Kimura et al (GenBank accession number: M33388). P34S and S486T amino acid substitutions were the characteristics of CYP2D6*10 allele. The relative activity of S9 fraction of HepG2-CYP2D6*10 metabolized detromethorphan O-demethylation was found to be 2.31 ± 0. 19 nmol·min-1·mg-1 S9 protein (n = 3), but was undetectable in parental HepG2 cells.
CONCLUSION: cDNA of human CYP2D6*10 can be successfully cloned. A cell line, HepG2-CYP2D6*10, expressing CYP2D6*10 mRNA and having metabolic activity, has been established.
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Affiliation(s)
- Jian Zhuge
- Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310031, Zhejiang Province, China
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Nazar-Stewart V, Vaughan TL, Stapleton P, Van Loo J, Nicol-Blades B, Eaton DL. A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer. Lung Cancer 2003; 40:247-58. [PMID: 12781423 DOI: 10.1016/s0169-5002(03)00076-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
A deletion polymorphism for glutathione S-transferase M1 (GSTM1) has been related to risk for lung cancer among smokers in some studies but not in others. We examined GSTM1, a GSTT1 deletion polymorphism and a common GSTP1 gene variant (iso-->val), as risk factors for lung cancer in a population-based case-control study of men. Cases (N=274) were males identified from 1993 to 1996 through the Fred Hutchinson Cancer Research Center Cancer Surveillance System registry for western Washington State. Male age-matched controls (N=501) were selected by random-digit dialing. Subjects participated in a telephone interview and blood draw. GSTM1 and GSTT1 were genotyped with a multiplex PCR assay using beta-globin as a positive control, and GSTP1 single nucleotide variant determined with PCR-based oligonucleotide ligation assays. GSTM1 absence was associated with a modest elevation in risk among all cases (odds ratio=1.27, 95% CI 0.91-1.77) and among non-small cell cancers (adenocarcinoma OR=1.58, 95% CI 0.99-2.52; squamous cell OR=1.40, 95% CI 0.83-2.34). Risk associated with GSTM1 null was increased two to sixfold among heavy smokers. GSTT1 was not associated with lung cancer risk and GSTP1 val was non-significantly associated with a modest reduction in risk, particularly among heavy smokers. No specific combination of GST genotypes was particularly associated with risk. These results support previous reports that the GSTM1 null genotype is associated with a modest increase in risk for lung cancer, particularly among heavy smokers, suggest no role for GSTT1 and the need for further study of GSTP1.
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Affiliation(s)
- Valle Nazar-Stewart
- Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97201, USA
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29
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Wang J, Deng Y, Li L, Kuriki K, Ding J, Pan X, Zhuge X, Jiang J, Luo C, Lin P, Tokudome S. Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: a case-control study in Chinese population. Cancer Sci 2003; 94:448-452. [PMID: 12824892 PMCID: PMC11160285 DOI: 10.1111/j.1349-7006.2003.tb01463.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2002] [Revised: 03/06/2003] [Accepted: 03/14/2003] [Indexed: 11/29/2022] Open
Abstract
A case-control study of 164 lung adenocarcinoma (AC) patients with 181 age- and gender-matched healthy controls was conducted in order to assess any associations between glutathione-S-transferase M1 (GSTM1), cytochrome P4501A1 (CYP1A1) and cytochrome P4502E1 (CYP2E1) polymorphisms and susceptibility to lung AC in Chinese. The presence of CYP2E1 variant allele was significantly less frequent in cases than in controls, while the distribution of GSTM1 null genotype and variant CYP1A1 Msp1 allele did not vary between cases and controls. After adjustment for age, gender, smoking and all other genotypes, the CYP2E1 Rsa1 variant allele was significantly associated with decreased risk of lung AC [odds ratio 0.534 (95% confidence interval, 0.340-0.837)]. Furthermore, 3.0-fold increased risk was found in individuals with combined GSTM1 null genotype and CYP2E1 Rsa1 wild type versus those with combined GSTM1 non-null type and CYP2E1 variant allele. Our results suggest that CYP2E1 Rsa1 variant allele is associated with a decreased risk of lung AC, and combined GSTM1 null genotype and CYP2E1 Rsa1 wild type has a promoting effect on susceptibility to lung AC.
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Affiliation(s)
- Jingwen Wang
- Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
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30
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Ruano-Ravina A, Figueiras A, Barros-Dios JM. Lung cancer and related risk factors: an update of the literature. Public Health 2003; 117:149-56. [PMID: 12825464 DOI: 10.1016/s0033-3506(02)00023-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
At the present time, lung cancer is the leading cause of cancer-related death in males. Diagnostic difficulty makes detection complicated and this, in conjunction with the low survival rate, renders the disease a serious health problem. In-depth knowledge of associated risk factors is therefore called for, in order to prevent or at least reduce the appearance of lung cancer and to open new avenues of research. Although the disease has a multicausal aetiology, tobacco accounts for 85-90% of all cases. This paper reviews the current situation, dividing the risk factors, for study purposes, into two groups; intrinsic (non-modifiable) and extrinsic (modifiable).
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Affiliation(s)
- A Ruano-Ravina
- Department of Preventive Medicine and Public Health, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, La Coruna 15705, Spain
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31
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Abstract
The health hazards due to exposure to environmental tobacco smoke (ETS) are increasingly established. ETS contains thousands of chemicals including 43 known carcinogens. One of the most important known health effects of ETS exposure is lung cancer in non-smokers, based on epidemiologic evidence and knowledge of the uptake and metabolism of ETS. Epidemiologic studies need to carefully take into account confounding and potential errors in exposure assessment. More research is needed to understand the genetic factors that influence ETS-induced lung cancer. Studies of the patterns of ETS exposure suggest higher rates of exposure in people employed as blue collar workers, in service occupations, earning lower incomes, and among the less educated. Certain racial/ethnic groups (e.g. Blacks, American Indians) may be at higher risk of ETS exposure. Despite substantial progress in protecting individuals from ETS exposure, additional efforts are needed in improving and enforcing policies to reduce exposure.
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Affiliation(s)
- Ross C Brownson
- Department of Community Health and Prevention Research Center, Saint Louis University School of Public Health, Salus Center, 3545 Lafayette Avenue, St Louis, Missouri, MO 63104, USA.
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32
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Benhamou S, Lee WJ, Alexandrie AK, Boffetta P, Bouchardy C, Butkiewicz D, Brockmöller J, Clapper ML, Daly A, Dolzan V, Ford J, Gaspari L, Haugen A, Hirvonen A, Husgafvel-Pursiainen K, Ingelman-Sundberg M, Kalina I, Kihara M, Kremers P, Le Marchand L, London SJ, Nazar-Stewart V, Onon-Kihara M, Rannug A, Romkes M, Ryberg D, Seidegard J, Shields P, Strange RC, Stücker I, To-Figueras J, Brennan P, Taioli E. Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk. Carcinogenesis 2002; 23:1343-50. [PMID: 12151353 DOI: 10.1093/carcin/23.8.1343] [Citation(s) in RCA: 180] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07-1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98-1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.
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Chen SS, Chang LS, Chen HW, Wei YH. Polymorphisms of glutathione S-transferase M1 and male infertility in Taiwanese patients with varicocele. Hum Reprod 2002; 17:718-25. [PMID: 11870126 DOI: 10.1093/humrep/17.3.718] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND To examine glutathione S-transferase M1 (GST M1) gene polymorphism and male infertility in Taiwanese patients with varicocele, 80 young male patients with varicocele (group 1), 62 young male patients with subclinical varicocele (group 2) and 60 normal young males (group 3) were recruited in this study. METHODS GST M1 null homozygous genotype [GST M1-] and the occurrence of a 4977 bp deletion of sperm mitochondrial DNA (mtDNA) were determined by polymerase chain reaction. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) content of sperm DNA was measured by high-performance liquid chromatography. RESULTS The frequencies of GST M1- genotype were 43.8, 41.9 and 45% for patients in groups 1, 2 and 3 respectively. In group 1 patients with GST M1- genotype, the frequency of the presence of the 4977 bp deletion in sperm mtDNA (54.3%) was significantly higher than that of the patients without the 4977 bp deletion in sperm mtDNA (45.7%, OR: 2.63, P = 0.04). Patients of groups 1 and 2 with GST M1- genotype had significantly higher 8-OHdG content in sperm DNA and lower protein thiols and ascorbic acid in seminal plasma than those with GST M1+ genotype. CONCLUSION GST M1- genotype predisposes to increased oxidative damage to sperm of patients with varicocele.
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Affiliation(s)
- Shiou-Sheng Chen
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, No. 155 Li-Nong Street, Sec. 2, Taichung, Taiwan, Republic of China
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