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Patil MN, Datkhile KD, Gudur AK, Gudur RA, Patil SR. Single-nucleotide polymorphism in CYP1A1, CYP1B1, CYP2B6, CYP2C8, and CYP2C9 genes and their association with gastrointestinal cancer: A hospital-based case-control study. J Cancer Res Ther 2024; 20:216-223. [PMID: 38554324 DOI: 10.4103/jcrt.jcrt_294_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 09/17/2022] [Indexed: 04/01/2024]
Abstract
BACKGROUND Cytochrome P450 (CYP) comprises a group of phase-I metabolizing enzymes that are important in xenobiotics metabolism. Genetic polymorphism of CYPs has been comprehensively studied for their association with a range of diseases. In this study, we assessed single-nucleotide polymorphism (SNP) of CYP1A, CYP1B, CYP2B, and CYP2C and their role in gastrointestinal (GI) cancer susceptibility in the rural population of Maharashtra. MATERIALS AND METHODS In this hospital-based case-control study, the association of polymorphism of CYP genes was studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study subjects included 200 clinically confirmed GI cancer patients and equal number of healthy controls. Odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to find out the level of association, where P ≤ 0.005 was considered statistically significant. RESULTS After the analysis of CYP1A1*2A (rs4646903), CYP1B1*3 (rs1059836), CYP2B6*5 (rs3211371), CYP2C8*2 (rs11572103), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), we noticed that variant (T) allele of CYP2B6*5 possessed significantly elevated risk (OR = 4.43; 95% CI: 2.20-8.90; P < 0.0001) of GI cancer in studied population. The genotypic distribution of G/C heterozygote allele of CYP1B1*3 (OR = 0.19, 95% CI = 0.12-0.32; P < 0.0001) and homozygous variant C/C allele (OR = 0.24, 95% CI = 0.13-0.45; P < 0.0001) showed a negative association with the development of GI cancer. CONCLUSION The findings from this study supported that polymorphism of CYP2B6*5gene may be involved in the development of GI cancer. However, other SNPs of CYP1A, CYP1B, and CYP2C genes did not signify the risk for GI cancer in the studied population of rural Maharashtra.
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Affiliation(s)
- Madhavi N Patil
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Satara, Maharashtra, India
| | - Kailas D Datkhile
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Satara, Maharashtra, India
| | - Anand K Gudur
- Department of Oncology, Krishna Institute of Medical Sciences "Deemed to be University", Satara, Maharashtra, India
| | - Rashmi A Gudur
- Department of Oncology, Krishna Institute of Medical Sciences "Deemed to be University", Satara, Maharashtra, India
| | - Satish R Patil
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Satara, Maharashtra, India
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Datkhile KD, Patil SR, Patil MN, Durgawale PP, Jagdale NJ, Deshmukh VN, More AL, Gudur RA, Gudur AK. Genetic polymorphisms of CYP1A, CYP1B, CYP2C and risk of cervical cancer among rural population of Maharashtra: Findings from a hospital-based case-control study. J Cancer Res Ther 2023; 19:1925-1930. [PMID: 38376298 DOI: 10.4103/jcrt.jcrt_292_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 04/29/2022] [Indexed: 02/21/2024]
Abstract
BACKGROUND Last few decades, multiple studies all over the world revealed the association of genetic polymorphism in cytochrome P450 (CYP) genes with risk of developing different type of cancers, but contradictory outcomes were evidenced in case of cervical cancer (CC) risk. Therefore, the discrepancies in earlier reports influenced us to evaluate the association of CYP1A1*2A rs4646903, CYP1B1*3 rs1056836, CYP2C8*2 rs11572103, CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP2C19*2 rs4244285 polymorphisms and CC susceptibility in the women of rural population of Maharashtra. MATERIALS AND METHODS In this case-control study, genetic association of the polymorphisms in CYP genes was studied by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted among 350 clinically confirmed CC patients and 350 healthy volunteers in a population of south-western Maharashtra. The odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to get the level of association where P ≤ 0.005 was considered as statistically significant. RESULTS After the analysis of single-nucleotide polymorphism (SNPs) of CYP1A1, CYP1B1, CYP2C8, CYP2C9, and CYP2C19, we noticed that CYP1B1*3 rs1056836 (Leu4326Val) polymorphism possessed a significantly elevated risk (OR = 3.28; 95% CI: 2.18-4.94; P < 0.0001), whereas CYP2C19*2 rs4244285 showed significantly lower risk (OR: 0.53, 95% CI: 0.33-0.85 P < 0.009) of CC in the studied rural population. CONCLUSION The findings from this study supported that rs1056836 SNP of CYP1B1*3 increase CC development, whereas rs4244285 of CYP2C19*2 lowers the CC risk in the studied population.
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Affiliation(s)
- Kailas D Datkhile
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Satish R Patil
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Madhavi N Patil
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Pratik P Durgawale
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Nilam J Jagdale
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Vinit N Deshmukh
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Ashwini L More
- Department of Molecular Biology and Genetics, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Rashmi A Gudur
- Department of Oncology, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
| | - Anand K Gudur
- Department of Oncology, Krishna Institute of Medical Sciences "Deemed to be University", Taluka-Karad, Dist- Satara, Maharashtra, India
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A decade in unravelling the etiology of gastric carcinogenesis in Kashmir, India – A high risk region. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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4
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Association between the SNPs in trace element-related metabolic genes and the risk of gastric cancer: a case–control study in Xianyou of China. J Genet 2019. [DOI: 10.1007/s12041-019-1110-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Chen S, Chen L, Tan Y, Wang J. Association between rs20417 polymorphism in cyclooxygenase-2 and gastric cancer susceptibility: Evidence from15 case-control studies. Medicine (Baltimore) 2019; 98:e15468. [PMID: 31045826 PMCID: PMC6504336 DOI: 10.1097/md.0000000000015468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVE Previous studies have reported an association between cyclooxygenase-2 (COX-2) polymorphism and gastric cancer (GC) susceptibility, but their results are controversial. This meta-analysis was intended to evaluate the relationship between the COX-2 rs20417 polymorphism and GC susceptibility in different ethnic groups. METHODS We searched PubMed, EMBASE, Web of Knowledge, and the Chinese Biomedical Database (CBM) for relevant case-control studies published up to October 6, 2018, which reported an association between the COX-2 rs20417 polymorphism and gastric cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association. RESULTS 15 papers detailing case-control studies were included in the analysis, which included a total of 2848 GC cases and 4962 healthy controls. The meta-analysis results indicated that the COX-2 rs20417 polymorphism was associated with increased GC susceptibility under allele (G vs C: OR = 1.67, 95%CI = 1.19-2.35, P = .003), heterozygous (GG vs CG: OR = 1.44, 95%CI = 1.03-2.02, P = .034), dominant (GC+CC vs GG: OR = 1.66, 95%CI = 1.18-2.34, P = .004), homozygous (GG vs CC:OR = 2.20, 95%CI = 1.07-4.54, P = .033), and recessive models (CC vs GG+CG:OR = 2.05, 95%CI = 1.09-3.85, P = .025). An analysis of ethnic subgroups revealed that the COX-2 rs20417 polymorphism was significantly associated with GC susceptibility in Asians under all 5 models (G vs C: OR = 2.22, 95%CI = 1.66-2.96, P < .001; GG vs CC: OR = 4.29, 95%CI = 1.94-9.50, P < .001; GG vs CG: OR = 1.86, 95%CI = 1.34-2.58, P < .001; CC vs GG+CG: OR = 3.73, 95%CI = 1.92-7.24, P < .001; GC+CC vs GG: OR = 2.20, 95%CI = 1.65-2.93, P < .001). Helicobacter pylori positive patients suffered a high risk of GC, compared to H pylori negative patients under the dominant model (OR = 3.09, 95%CI = 1.80-5.32, P < .001). CONCLUSION This meta-analysis of 15 case-control studies provides strong evidence that the COX-2 rs20417 polymorphism increases the risk of GC susceptibility in general populations, especially in Asians. Helicobacter pylori positive patients and those with the COX-2 rs20417 polymorphism had a higher risk of developing GC.
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Affiliation(s)
- Shimin Chen
- Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi
- Department of Gastroenterology, Affiliated Hospital of Shaanxi Chinese Medicine University, Xianyang, China
| | - Lu Chen
- Department of Gastroenterology, Affiliated Hospital of Shaanxi Chinese Medicine University, Xianyang, China
| | - Yuling Tan
- Department of Gastroenterology, Affiliated Hospital of Shaanxi Chinese Medicine University, Xianyang, China
| | - Jiehong Wang
- Department of Gastroenterology, Affiliated Hospital of Shaanxi Chinese Medicine University, Xianyang, China
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Mandal RK, Mittal RD. Glutathione S-Transferase P1 313 (A > G) Ile105Val Polymorphism Contributes to Cancer Susceptibility in Indian Population: A Meta-analysis of 39 Case-Control Studies. Indian J Clin Biochem 2018; 35:8-19. [PMID: 32071492 DOI: 10.1007/s12291-018-0787-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Accepted: 09/08/2018] [Indexed: 12/17/2022]
Abstract
GSTP1 involved in the metabolism of carcinogens and toxins, reduces damage of DNA and act as a suppressor of carcinogenesis. Many studies have reported that 313 A > G polymorphism is associated with different cancer in Indian population, but the results remain conflicting rather than conclusive. Therefore, we have performed meta-analysis to clarify the more precise association of GSPT1 313 A > G polymorphism with cancer risk in Indian population. We retrieved all relevant published literature from PubMed (Medline) and Google scholar web database and included those study only based on the established inclusion criteria. Pooled ORs and 95% CIs were used to appraise the strength of association. Publication bias and sensitivity analysis was also evaluated. A total of 6581 confirmed cancer cases and 8218 controls were included from eligible thirty nine case-controls studies. Pooled analysis suggested that the variant genotypes significantly increased the risk of cancer in allele (G vs. A: OR 1.266, 95% CI 1.129-1.418, p = 0.001), heterozygous (AG vs. AA: OR 1.191, 95% CI 1.047-1.355, p = 0.008), homozygous (GG vs. AA: OR 1.811, 95% CI 1.428-2.297, p = 0.001), dominant (GG + AG vs. AA: OR 1.276, 95% CI 1.110-1.466, p = 0.001) and recessive (GG vs. AG + AA: OR 1.638, 95% CI 1.340-2.002, p = 0.001) genetic models. The stability of these observations was confirmed by a sensitivity analysis. Begger's funnel plot and Egger's test did not reveal any publication bias. This meta-analysis suggests that the GSTP1 313 A > G polymorphism may contribute to genetic susceptibility to cancer in Indian population. However, larger studies and randomized clinical trial will be required to elucidate the biological and molecular mechanism of GSTP1 gene in cancer.
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Affiliation(s)
- Raju K Mandal
- 1Research and Scientific Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.,2Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Rama D Mittal
- 2Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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Du L, Lei L, Zhao X, He H, Chen E, Dong J, Zeng Y, Yang J. The Interaction of Smoking with Gene Polymorphisms on Four Digestive Cancers: A Systematic Review and Meta-Analysis. J Cancer 2018; 9:1506-1517. [PMID: 29721061 PMCID: PMC5929096 DOI: 10.7150/jca.22797] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 01/22/2018] [Indexed: 12/15/2022] Open
Abstract
The main purpose of this study was to perform a meta-analysis to assess the interaction between smoking and nine genes (GSTM1, GSTT1, GSTP1, CYP1A1, NAT2, SULT1A1, hOGG1, XRCC1 and p53) on colorectal cancer, gastric cancer, liver cancer and oesophageal cancer. Published articles from the PubMed, ISI and EMBASE databases were retrieved. A total of 67 case-control studies or nested case-control studies were identified for the analysis. The pooled jodds ratio (OR) with 95% confidence interval (CI) was calculated using the random effect model. The overall study showed that the GSTM1 polymorphism was associated with the risk of the four digestive cancers among Asian population (OR 1.284, 95% CI: 1.122-1.470, p: 0). Subgroup analyses by cancer site showed that GSTM1 null genotype increased the gastric cancer risk in total population (OR 1.335, 95% CI: 1.145-1.556, p: 0). However, the association of GSTM1 null genotype with the oesophageal cancer risk was found in smokers (OR 1.382, 95% CI: 1.009-1.894, p:0.044), but not in non-smokers (OR 1.250, 95% CI: 0.826-1.891, p:0.290). Moreover, smokers with the CYP1A1 IIe462Val polymorphism were at an increased cancer risk in Asian population (OR=1.585, 95% CI 1.029-2.442, p: 0.037). None of the other gene-smoking interactions was observed in the above cancers. This meta-analysis reveals two potential gene-smoking interactions, one is between smoking and GSTM1 on oesophageal cancer, and the other is between smoking and CYP1A1 IIe462Val on the four cancers in Asian population. Future studies need to be conducted to verify the conclusions.
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Affiliation(s)
- Le Du
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Lei Lei
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Xiaojuan Zhao
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Hongjuan He
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Erfei Chen
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Jing Dong
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Yuan Zeng
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Jin Yang
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
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Sang L, Lv Z, Sun LP, Xu Q, Yuan Y. Impact of SNP-SNP interactions of DNA repair gene ERCC5 and metabolic gene GSTP1 on gastric cancer/atrophic gastritis risk in a Chinese population. World J Gastroenterol 2018; 24:602-612. [PMID: 29434449 PMCID: PMC5799861 DOI: 10.3748/wjg.v24.i5.602] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 12/05/2017] [Accepted: 12/12/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5 (ERCC5) and the metabolic gene glutathione S-transferase pi 1 (GSTP1) and their effects on atrophic gastritis (AG) and gastric cancer (GC) risk.
METHODS Seven ERCC5 single nucleotide polymorphisms (SNPs) (rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassARRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population.
RESULTS Two pairwise combinations (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk (Pinteraction = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility (Ptrend > 0.05). When the modification effect of Helicobacter pylori (H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions (ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status (Ptrend = 0.043).
CONCLUSION There is a multifarious interaction between the DNA repair gene ERCC5 SNPs (rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.
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Affiliation(s)
- Liang Sang
- Department of Ultrasound, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Ping Sun
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, Liaoning Province, China
- National Clinical Research Center for Digestive Diseases, Xi’an 710032, Shaanxi Province, China
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, Liaoning Province, China
- National Clinical Research Center for Digestive Diseases, Xi’an 710032, Shaanxi Province, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, Liaoning Province, China
- National Clinical Research Center for Digestive Diseases, Xi’an 710032, Shaanxi Province, China
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Ribeiro RX, Nascimento CILL, Silva AMTC. GENOTYPE ASSOCIATION GSTM1 NULL AND GASTRIC CANCER: EVIDENCE-BASED META-ANALYSIS. ARQUIVOS DE GASTROENTEROLOGIA 2017; 54:101-108. [PMID: 28327825 DOI: 10.1590/s0004-2803.201700000-14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 12/05/2016] [Indexed: 02/12/2023]
Abstract
BACKGROUND Gastric cancer is the fourth most common cancer in men and the sixth among women, except for non-melanoma skin tumors, in Brazil. Epidemiological evidences reveal the multifactorial etiology of this cancer, highlighting risk factors such as: infection by the bacterium Helicobacter pylori, advanced age, smoking, chronic alcohol abuse, eating habits and genetic polymorphisms. Considering the context of genetic polymorphisms, there is the absence of the GSTM1 gene. The lack of GSTM1 function to detoxify xenobiotics and promote defense against oxidative stress leads to increased DNA damage, promoting gastric carcinogenesis. This process is multifactorial and the development of gastric cancer results from a complex interaction of these variables. OBJECTIVE The aim of this study was to investigate the association of GSTM1 null polymorphism in the pathogenesis of gastric cancer. METHODS A meta-analysis was conducted from 70 articles collected in SciELO and PubMed databases, between September 2015 and July 2016. In order to evaluate a possible association, we used the odds ratio (OR) and confidence interval of 95% (CI 95%). To assess the heterogeneity of the studies was used the chi-square test. Statistical analysis was performed using the BioEstat® 5.3. RESULTS This study included 70 studies of case-control, including 28,549 individuals, which were assessed for the null polymorphism of the GSTM1 gene, and of which 11,208 (39.26%) were cases and 17,341 (60.74%) were controls. The final analysis showed that the presence of the GSTM1 gene acts as a protective factor against the development of gastric cancer (OR=0.788; 95%CI 0.725-0.857; P<0.0001). Positive statistical association was found in Asia (OR=0.736; 95%CI 0.670-0.809; P<0.0001) and Eurasia (OR=0.671; 95%CI 0.456-0.988; P=0.05). However, statistically significant data was not obtained in Europe (OR=1.033; 95%CI 0.873-1.222; P=0.705) and America (OR=0.866; 95%CI 0.549-1.364; P=0.534). Therefore, the results can not be deduced around the world. CONCLUSION This meta-analysis concluded that the presence of the GSTM1 gene is a protector for the emergence of gastric cancer, especially in Asian countries, but this result was not found in Europe and America.
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Affiliation(s)
- Rívian Xavier Ribeiro
- Departamento de Medicina, Escola de Ciências Médicas, Farmacêuticas e Biomédicas, Pontifícia Universidade Católica de Goiás (PUC-GO), Goiânia, GO, Brazil
| | - Cícera Isabella Leão Leite Nascimento
- Departamento de Medicina, Escola de Ciências Médicas, Farmacêuticas e Biomédicas, Pontifícia Universidade Católica de Goiás (PUC-GO), Goiânia, GO, Brazil
| | - Antonio Márcio Teodoro Cordeiro Silva
- Departamento de Medicina, Escola de Ciências Médicas, Farmacêuticas e Biomédicas, Pontifícia Universidade Católica de Goiás (PUC-GO), Goiânia, GO, Brazil
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Ghatak S, Yadav RP, Lalrohlui F, Chakraborty P, Ghosh S, Ghosh S, Das M, Pautu JL, Zohmingthanga J, Senthil Kumar N. Xenobiotic Pathway Gene Polymorphisms Associated with Gastric Cancer in High Risk Mizo-Mongoloid Population, Northeast India. Helicobacter 2016; 21:523-535. [PMID: 27006283 DOI: 10.1111/hel.12308] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the risk of gastric cancer associated with individual or combined glutathione S-transferases (GSTs) polymorphism and their interaction with environmental factors. MATERIALS AND METHODS Genotyping by PCR was carried out for 80 cases and controls each for GSTM1, GSTT1, and GSTP1 polymorphism and mapped for gene-environment association studies. The samples were subjected to pathogen detection and GSTP1 expression for analyzing their association with different genotypes. Logistic regression analyses were conducted to compute the influence of both genetic and environmental factors for gastric cancer. MDR analysis was performed to assess the risk of gastric cancer by studying the gene-gene and gene-environment effect on the basis of GST genotyping and GSTP1 gene expression. RESULTS Infection with Helicobacter pylori and CagA+ strains was more frequent in patients with GSTM1/T1 null genotype. Intake of high fermented fat and smoked meat was found to be significantly associated with gastric cancer. The G/G, A/G (rs1695), and T/T (rs1138272) were found to be significantly associated with low expression of GSTP1 gene in cancer tissue. CONCLUSION Presence of H. pylori with CagA genotype showed significant individual effect with GSTT1 polymorphism as well as strong synergistic effect in gastric cancer risk. Majority of the gastric cancer samples showed significant negative expression in G/G, A/G (rs1695), and T/T (rs1138272) genotypes. This study shows that GST gene polymorphism was significantly relevant for determining the individual susceptibility to gastric cancer.
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Affiliation(s)
- Souvik Ghatak
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | | | - Freda Lalrohlui
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Payel Chakraborty
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Soumee Ghosh
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
| | - Sudakshina Ghosh
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
| | - Madhusudan Das
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
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Zeng Y, Bai J, Deng LC, Xie YP, Zhao F, Huang Y. Association of the Glutathione S-transferase T1 Null Genotype with Risk of Gastric Cancer: a Meta-analysis in Asian Populations. Asian Pac J Cancer Prev 2016; 17:1141-8. [DOI: 10.7314/apjcp.2016.17.3.1141] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Ren A, Qin T, Wang Q, Du H, Zhong D, Hua Y, Zhu L. Cytochrome P450 1A1 gene polymorphisms and digestive tract cancer susceptibility: a meta-analysis. J Cell Mol Med 2016; 20:1620-31. [PMID: 27061602 PMCID: PMC4988294 DOI: 10.1111/jcmm.12853] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 02/25/2016] [Indexed: 12/21/2022] Open
Abstract
Cytochrome P450 1A1 (CYP1A1) is a phase I enzyme that regulates the metabolism of environmental carcinogens and alter the susceptibility to various cancers. Many studies have investigated the association between the CYP1A1 MspI and Ile462Val polymorphisms and digestive tract cancer (DTC) risk in different groups of populations, but their results were inconsistent. The PubMed and Embase Database were searched for case–control studies published up to 30th September, 2015. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the relationship. Totally, 39 case–control studies (9094 cases and 12,487 controls) were included. The G allele in Ile/Val polymorphism was significantly associated with elevated DTC risk with per‐allele OR of 1.24 (95% CI = 1.09–1.41, P = 0.001). Similar results were also detected under the other genetic models. Evidence was only found to support an association between MspI polymorphism and DTC in the subgroups of caucasian and mixed individuals, but not in the whole population (the dominant model: OR = 1.19, 95% CI = 0.94–1.91, P = 0.146). In conclusion, our results suggest that the CYP1A1 polymorphisms are potential risk factors for DTC. And large sample size and well‐designed studies with detailed clinical information are needed to more precisely evaluate our founding.
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Affiliation(s)
- Anjing Ren
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Tingting Qin
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qianqian Wang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Haina Du
- Department of Oncology, The Third Affiliated Hospital of Nanjing University of T.C.M, Nanjing, China
| | - Donghua Zhong
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yibing Hua
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lingjun Zhu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Zhang MX, Liu K, Wang FG, Wen XW, Song XL. Association between CYP2E1 polymorphisms and risk of gastric cancer: An updated meta-analysis of 32 case-control studies. Mol Clin Oncol 2016; 4:1031-1038. [PMID: 27284439 DOI: 10.3892/mco.2016.824] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Accepted: 03/03/2016] [Indexed: 01/01/2023] Open
Abstract
Previous studies suggested that RsaI/PstI and DraI polymorphisms on cytochrome P450 2E1 (CYP2E1) may be associated with susceptibility to gastric cancer (GC). However, this association remains ambiguous. A meta-analysis of previously published studies was performed in an attempt to elucidate this association. The odds ratio and 95% confidence interval were used to assess the strength of the association. In the overall analyses of RsaI/PstI and DraI, no association was identified. In the subgroup analyses, RsaI/PstI was identified to increase the risk of GC in the smoking population. In addition, in the previous studies of interactions with other genes, RsaI/PstI was revealed to be associated with increased GC risks when glutathione S-transferase-µ-1 or glutathione S-transferase θ-1 was null or DraI was homozygous wild-type. However, these stratified analyses were lacking credibility due to the limitation of correlational study numbers. In conclusion, CYP2E1 polymorphisms revealed no association with the risk of GC.
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Affiliation(s)
- Ming-Xing Zhang
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China; Department of Gastrointestinal Surgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Kai Liu
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China
| | - Fu-Gang Wang
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China
| | - Xiao-Wen Wen
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China
| | - Xi-Lin Song
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China
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Ghosh S, Ghosh S, Bankura B, Saha ML, Maji S, Ghatak S, Pattanayak AK, Sadhukhan S, Guha M, Nachimuthu SK, Panda CK, Maity B, Das M. Association of DNA repair and xenobiotic pathway gene polymorphisms with genetic susceptibility to gastric cancer patients in West Bengal, India. Tumour Biol 2016; 37:9139-49. [PMID: 26768611 DOI: 10.1007/s13277-015-4780-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 12/29/2015] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95 % confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95 % CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95 % CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95 % CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.
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Affiliation(s)
- Soumee Ghosh
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Sudakshina Ghosh
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Biswabandhu Bankura
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Makhan Lal Saha
- Department of Surgery, Institute of Post Graduate Medical Education & Research, 244 A.J.C Bose Road, Kolkata, 700 020, West Bengal, India
| | - Suvendu Maji
- Department of Surgery, Institute of Post Graduate Medical Education & Research, 244 A.J.C Bose Road, Kolkata, 700 020, West Bengal, India
| | - Souvik Ghatak
- Department of Biotechnology, Mizoram University, Tanhril, Aizawl, Mizoram, P.O. Box No. 190, India
| | - Arup Kumar Pattanayak
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Susanta Sadhukhan
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Manalee Guha
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Senthil Kumar Nachimuthu
- Department of Biotechnology, Mizoram University, Tanhril, Aizawl, Mizoram, P.O. Box No. 190, India
| | - Chinmay Kumar Panda
- Department of Oncogene Regulation and Viral Associated Human Cancer, Chittaranjan Cancer Research Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, West Bengal, India
| | - Biswanath Maity
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Madhusudan Das
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India.
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Darnet S, Moreira FC, Hamoy IG, Burbano R, Khayat A, Cruz A, Magalhães L, Silva A, Santos S, Demachki S, Assumpção M, Assumpção P, Ribeiro-Dos-Santos Â. High-Throughput Sequencing of miRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers. Bioinform Biol Insights 2015; 9:1-8. [PMID: 26157332 PMCID: PMC4485834 DOI: 10.4137/bbi.s23773] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 03/29/2015] [Accepted: 04/01/2015] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer has a high incidence and mortality rate worldwide; however, the use of biomarkers for its clinical diagnosis remains limited. The microRNAs (miRNAs) are biomarkers with the potential to identify the risk and prognosis as well as therapeutic targets. We performed the ultradeep miRnomes sequencing of gastric adenocarcinoma and gastric antrum without tumor samples. We observed that a small set of those samples were responsible for approximately 80% of the total miRNAs expression, which might represent a miRNA tissue signature. Additionally, we identified seven miRNAs exhibiting significant differences, and, of these, hsa-miR-135b and hsa-miR-29c were able to discriminate antrum without tumor from gastric cancer regardless of the histological type. These findings were validated by quantitative real-time polymerase chain reaction. The results revealed that hsa-miR-135b and hsa-miR-29c are potential gastric adenocarcinoma occurrence biomarkers with the ability to identify individuals at a higher risk of developing this cancer, and could even be used as therapeutic targets to allow individualized clinical management.
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Affiliation(s)
- Sylvain Darnet
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Fabiano C Moreira
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Área de Ciências Exatas e Tecnológicas, Centro Universitário do Pará, Belém, PA, Brazil
| | - Igor G Hamoy
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Universidade Federal Rural da Amazônia, Campus de Capanema, PA, Brazil
| | - Rommel Burbano
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
| | - André Khayat
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
| | - Aline Cruz
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Leandro Magalhães
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Artur Silva
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Sidney Santos
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
| | - Samia Demachki
- Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil. ; Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, PA, Brazil
| | - Monica Assumpção
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil
| | - Paulo Assumpção
- Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil. ; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil
| | - Ândrea Ribeiro-Dos-Santos
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
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Lao X, Peng Q, Lu Y, Li S, Qin X, Chen Z, Chen J. Glutathione S-transferase gene GSTM1, gene-gene interaction, and gastric cancer susceptibility: evidence from an updated meta-analysis. Cancer Cell Int 2014; 14:127. [PMID: 25477765 PMCID: PMC4255933 DOI: 10.1186/s12935-014-0127-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Accepted: 11/10/2014] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The null genotype of GSTM1 have been implicated in gastric cancer risk, but numerous individual studies showed mixed, or even conflicting results. Thus, a meta-analysis was performed. RESULTS We identified 54 individual studies involving 9,322 cases and 15,118 controls through computer-based searches of PubMed, Embase, and Cochrane Library. It was found that the null genotype of GSTM1 was associated with an increased gastric cancer risk (OR = 1.207, 95% CI: 1.106-1.317, P < 0.001), under the random-effects model (I(2) : 49.9%, PQ <0.001). From stratification analyses for ethnicity, alcohol drinking, Helicobacter pylori infection, an effect modification of gastric cancer risk was found in the subgroups of ethnicity, smoking status, Helicobacter pylori infection, whereas null result was found in the subgroups of alcohol drinking. We also undertook gene-gene interaction analysis between GSTM1 and GSTT1 genes for gastric cancer risk, and the results indicated that the dual null genotypes of GSTM1 and GSTT1 might elevate the risk of gastric cancer (OR = 1.505, 95% CI: 1.165-1.944, P = 002). CONCLUSIONS This meta-analysis suggests that the null genotype of GSTM1 may be a important genetic risk factor for gastric cancer development.
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Affiliation(s)
- Xianjun Lao
- />Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region China
| | - Qiliu Peng
- />Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region China
| | - Yu Lu
- />Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region China
| | - Shan Li
- />Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region China
| | - Xue Qin
- />Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region China
| | - Zhiping Chen
- />Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region China
| | - Junqiang Chen
- />Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region China
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Malik MA, Srivastava P, Zargar SA, Mittal B. Phospholipase C epsilon 1 (PLCE1) haplotypes are associated with increased risk of gastric cancer in Kashmir Valley. Saudi J Gastroenterol 2014; 20:371-377. [PMID: 25434319 PMCID: PMC4271013 DOI: 10.4103/1319-3767.145330] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2014] [Accepted: 07/18/2014] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND/AIM Phospholipase C epsilon 1 (PLCE1) plays a crucial role in carcinogenesis and progression of several types of cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. The aim of the present study was to investigate the role of three potentially functional SNPs (rs2274223A > G, rs3765524C > T, and rs7922612C > T) of PLCE1 in gastric cancer patients from Kashmir Valley. PATIENTS AND METHODS The study was conducted in 108 GC cases and 195 healthy controls from Kashmir Valley. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed using c2 test and logistic regression models. A P value of less than 0.05 was regarded as statistically significant. RESULTS The frequency of PLCE1 A2274223C3765524T7922612, G2274223C3765524T7922612 , and G2274223T3765524C7922612 haplotypes were higher in patients compared with controls, conferred high risk for GC [odds ratio (OR) =6.29; P = 0.001; Pcorr = 0.003], (OR = 3.23; P = 0.011; Pcorr = 0.033), and (OR = 5.14; P = 0.011; Pcorr = 0.033), respectively. Smoking and salted tea are independent risk factors for GC, but we did not find any significant modulation of cancer risk by PLCE1 variants with smoking or excessive consumption of salted tea. CONCLUSION These results suggest that variation in PLCE1 may be associated with GC risk in Kashmir Valley.
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Affiliation(s)
- Manzoor A. Malik
- Department of Ocular Biochemistry, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, Uttar Pradesh, India
| | - Priya Srivastava
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, Uttar Pradesh, India
| | - Showkat A. Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, Uttar Pradesh, India
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Meng X, Liu Y, Liu B. Glutathione S-transferase M1 null genotype meta-analysis on gastric cancer risk. Diagn Pathol 2014; 9:122. [PMID: 24948179 PMCID: PMC4079641 DOI: 10.1186/1746-1596-9-122] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Accepted: 03/22/2014] [Indexed: 12/20/2022] Open
Abstract
Background Glutathione S-transferases (GSTs) have proved to be involved in the detoxifying several carcinogens and may play an important role in carcinogenesis of cancer. Previous studies on the association between Glutathione S-transferase M1 (GSTM1) polymorphism and gastric cancer (GC) risk reported inconclusive results. To get a precise result, we conducted this present meta-analysis through pooling all eligible studies. Methods A comprehensive databases of Pubmed, Embase, Web of Science, and the Chinese Biomedical Database (CBM) were searched for case–control studies investigating the association between GSTM1 null genotype and GC risk. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to assess this possible association. A χ2-based Q-test was used to examine the heterogeneity assumption. Begg’s and Egger’s test were used to examine the potential publication bias. The leave-one-out sensitivity analysis was conducted to determine whether our assumptions or decisions have a major effect on the results of present work. Statistical analyses were performed with the software program STATA 12.0. Results A total of 47 eligible case–control studies were identified, including 6,678 cases and 12,912 controls. Our analyses suggested that GSTM1 null genotype was significantly associated with increased risk of GC (OR = 1.186, 95% CI = 1.057-1.329, Pheterogenetiy = 0.000, P = 0.004). Significant association was also found in Asians (OR = 1.269, 95% CI = 1.106-1.455, Pheterogenetiy = 0.002, P = 0.001). However, GSTM1 null genotype was not contributed to GC risk in Caucasians (OR = 1.115, 95% CI = 0.937-1.326, Pheterogenetiy = 0.000, P = 0.222). In the subgroup analysis stratified by sources of controls, significant association was detected in hospital-based studies (OR = 1.355, 95% CI = 1.179-1.557, Pheterogenetiy = 0.001, P = 0.000), while there was no significant association detected in population-based studies (OR = 1.017, 95% CI = 0.862-1.200, Pheterogenetiy = 0.000, P = 0.840). Conclusion This meta-analysis showed the evidence that GSTM1 null genotype contributed to the development of GC. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1644180505119533.
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Affiliation(s)
| | - Yong Liu
- Department of Gastroenterology, Affiliated to the Fourth Hospital of Harbin Medical University, Harbin 150001, China.
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Yoon J, Hyun MH, Yang JP, Park MJ, Park S. Ethnic differences in the association of the glutathione S-transferase T1 (GSTT1) null genotype and risk of gastric carcinoma: a systematic review and meta-analysis. Mol Biol Rep 2014; 41:3867-79. [DOI: 10.1007/s11033-014-3254-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Accepted: 02/08/2014] [Indexed: 12/30/2022]
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The effect of CYP1A1 and CYP1A2 polymorphisms on gastric cancer risk among different ethnicities: a systematic review and meta-analysis. Tumour Biol 2014; 35:4741-56. [PMID: 24443269 DOI: 10.1007/s13277-014-1620-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 01/03/2014] [Indexed: 01/04/2023] Open
Abstract
Potential Cytochrome P450s (CYPs) 1A1 MspI, 1A1 Ile462Val, 1A2*1 F, and/or 1A2*1C polymorphisms have been implicated in gastric cancer risk among different ethnicities. We aimed to explore the effect of CYP 1A1 MspI, 1A1 Ile462Val, 1A2*1 F, and/or 1A2*1C polymorphisms on the susceptibility to gastric cancer among different ethnicities through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. A number of 11 studies were ultimately eligible for the meta-analysis of CYP1A1 MspI polymorphism, eight studies for the meta-analysis of 1A1 Ile462Val polymorphism, and two studies for the meta-analysis of 1A2*1 F polymorphism. None of genetic model was evidently suggested, and thus all the genetic models were presented. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication biases were estimated. In our meta-analysis, significant results could be found in mutational heterozygous CT genotype, compared with wild TT genotype, among large sample size subgroup for CYP1A1 MspI polymorphism. Regarding CYP1A1 Ile462Val polymorphism, no statistically significant results could be found. For CYP1A2*1 F polymorphism, mutational heterozygous AC genotype, compared with wild-type AA, has deleterious effects, whereas mutational homozygous CC genotype, compared with mutational heterozygous type AC, has protective effects but lacks statistically significant difference despite its a proximity to 0.05. Combined mutational homozygous CC genotype and wild-type homozygous AA, compared with mutational heterozygous AC genotype, has protective effects. Our meta-analysis suggests no associations between CYP1A1 Ile462Val polymorphism and gastric cancer, but possible associations between CYP1A1 MspI and CYP1A2*1 F polymorphisms and gastric cancer, which needs to be further reinforced or refuted among different ethnicities in well-designed large-scale high-quality studies.
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Association between the CYP1A1 T3801C polymorphism and risk of cancer: Evidence from 268 case–control studies. Gene 2014. [PMID: 24498651 DOI: 10.1016/j.gene.2013.10.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Malakar M, Devi KR, Phukan RK, Kaur T, Deka M, Puia L, Baruah D, Mahanta J, Narain K. CYP2E1 genetic polymorphism with dietary, tobacco, alcohol habits, H. pylori infection status and susceptibility to stomach cancer in Mizoram, India. Asian Pac J Cancer Prev 2014; 15:8815-22. [PMID: 25374213 DOI: 10.7314/apjcp.2014.15.20.8815] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2023] Open
Abstract
BACKGROUND The incidence of stomach cancer in India is highest in the state of Mizoram. In this population based matched case-control study, we evaluated the relationship between CYP450 2E1 RsaI polymorphism and risk of stomach cancer taking into considering various important dietary habits along with tobacco, alcohol consumption and H. pylori infection status. MATERIALS AND METHODS A total of 105 histologically confirmed stomach cancer cases and 210 matched healthy population controls were recruited. CYP2E1 RsaI genotypes were determined by PCR-RFLP and H. pylori infection status by ELISA. Information on various dietary, tobacco and alcohol habits was recorded in a standard questionnaire. RESULTS Our study revealed no significant association between the CYP2E1 RsaI polymorphism and overall risk of stomach cancer in Mizoram. However, we observed a non-significant protective effect of the variant allele (A) of CYP2E1 against stomach cancer. Tobacco smokers carrying C/C genotype have three times more risk of stomach cancer, as compared to non-smokers carrying C/C genotype. Both Meiziol and cigarette current and past smokers who smoked for more than 10 times per day and carrying the (C/C) genotype are more prone to develop stomach cancer. Smoke dried fish and preserved meat (smoked/sun dried) consumers carrying C/C genotype possesses higher risk of stomach cancer. No significant association between H. pylori infection and CYP2E1 RsaI polymorphism in terms of stomach cancer was observed. CONCLUSIONS Although no direct association between the CYP2E1 RsaI polymorphism and stomach cancer was observed, relations with different tobacco and dietary risk habits in terms of developing stomach cancer exist in this high risk population of north-eastern part of India. Further in-depth study recruiting larger population is required to shed more light on this important problem.
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Affiliation(s)
- Mridul Malakar
- Regional Medical Research Centre, NE Region (Indian Council of Medical Research), Dibrugarh, Assam, India E-mail :
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Malik MA, Umar M, Gupta U, Zargar SA, Mittal B. Phospholipase C epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) polymorphisms and esophageal cancer risk in the Kashmir Valley. Asian Pac J Cancer Prev 2014; 15:4319-4323. [PMID: 24935391 DOI: 10.7314/apjcp.2014.15.10.4319] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area. MATERIALS AND METHODS We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS. RESULTS The selected PLCE1 polymorphisms did not show independent association with EC. However, the G2274223T3765524T7922612 haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC. CONCLUSIONS Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India E-mail : ,
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Meta-analysis of the association of glutathione S-transferase T1 null/presence gene polymorphism with the risk of gastric carcinoma. Mol Biol Rep 2013; 41:639-49. [PMID: 24352702 DOI: 10.1007/s11033-013-2902-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Accepted: 12/10/2013] [Indexed: 12/23/2022]
Abstract
A possible association of glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and an increased risk of developing gastric carcinoma is still unclear and hotly debated. This investigation was performed to assess the association of the GSTT1 null/presence gene polymorphism with the risk of gastric carcinoma via a meta-analysis to increase sample size and statistical significance. PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) were searched on March 1, 2013, association reports were identified, and eligible studies were recruited and synthesized. Fifty-two reports were found to be suitable for this meta-analysis for the association of the GSTT1 null genotype with gastric carcinoma risk. The results showed that there was a significantly increased gastric carcinoma risk when the GSTT1 null genotype was present in the overall population (OR 1.21, 95 % CI 1.11-1.32, P < 0.0001), Caucasians (OR 1.25, 95 % CI 1.05-1.48, P = 0.01), East-Asians (OR 1.18, 95 % CI 1.06-1.31, P = 0.003), and Chinese (OR 1.24, 95 % CI 1.07-1.44, P = 0.005). However, no statistically relevant association could be established for the Indian ethnic group (OR 1.33, 95 % CI 0.94-1.90, P = 0.11). In conclusion, the GSTT1 null genotype is associated with an increased gastric carcinoma risk in the overall population, Caucasians, East-Asians, and Chinese.
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Gu J, Zou H, Zheng L, Li X, Chen S, Zhang L. GSTM1 null genotype is associated with increased risk of gastric cancer in both ever-smokers and non-smokers: a meta-analysis of case-control studies. Tumour Biol 2013; 35:3439-45. [PMID: 24318990 DOI: 10.1007/s13277-013-1454-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Accepted: 11/19/2013] [Indexed: 01/16/2023] Open
Abstract
Previous studies have suggested that the glutathione S-transferases M1 (GSTM1) null genotype is associated with the risk of gastric cancer. However, the interaction between GSTM1 null genotype and smoking for the risk of gastric cancer is still elusive. Therefore, we performed a meta-analysis to ascertain this issue. Databases of PubMed, EMBASE, and China National Knowledge Infrastructure were searched to retrieve relevant studies. Smokers were categorized as "ever-smokers" and "non-smokers." Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to estimate the association strength. Subgroup analyses according to ethnicity, source of control, and sample size were also conducted. A total of 15 eligible studies, including 4,687 gastric cancer cases and 7,002 controls, were identified. We found that the GSTM1 null genotype was associated with increased risk of gastric cancer among ever-smokers (OR = 1.460, 95% CI 1.064-2.003, heterogeneity: P = 0.019). The null genotype also significantly increased the risk of gastric cancer among non-smokers (OR = 1.777, 95% CI 1.301-2.426, heterogeneity: P < 0.01). Stratified analysis according to ethnicity showed that the GSTM1 null genotype was associated with increased risk of gastric cancer among Asians both in ever-smokers (OR = 1.841, 95% CI 1.184-2.861) and non-smokers (OR = 1.773, 95% CI 1.382-2.275). In conclusion, the GSMT1 null genotype significantly increased the risk of gastric cancer both in ever-smokers and non-smokers.
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Affiliation(s)
- Jianchun Gu
- Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China
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Zhao Y, Deng X, Song G, Qin S, Liu Z. The GSTM1 null genotype increased risk of gastric cancer: a meta-analysis based on 46 studies. PLoS One 2013; 8:e81403. [PMID: 24244742 PMCID: PMC3820558 DOI: 10.1371/journal.pone.0081403] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Accepted: 10/16/2013] [Indexed: 01/08/2023] Open
Abstract
Background Glutathione S-transferases M1 (GSTM1) is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk. Methods This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren’s classification, and other factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Results A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, Pheterogeneity<0.001). Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, Pheterogeneity = 0.002), but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, Pheterogeneity=0.065), while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, Pheterogeneity=0.168). For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren’s classification did not modify the association. Conclusions In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.
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Affiliation(s)
- Yi Zhao
- Department of Pancreato-Breast Surgery, Affiliated Shengjing Hospital of China Medical University, Shenyang, China
- * E-mail:
| | - Xin Deng
- Department of Pancreato-Breast Surgery, Affiliated Shengjing Hospital of China Medical University, Shenyang, China
| | - Guoqing Song
- Department of Pancreato-Breast Surgery, Affiliated Shengjing Hospital of China Medical University, Shenyang, China
| | - Shibo Qin
- Department of Pancreato-Breast Surgery, Affiliated Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhanzhan Liu
- Department of Pancreato-Breast Surgery, Affiliated Shengjing Hospital of China Medical University, Shenyang, China
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Malik MA, Gupta A, Zargar SA, Mittal B. Role of genetic variants of deleted in colorectal carcinoma (DCC) polymorphisms and esophageal and gastric cancers risk in Kashmir Valley and meta-analysis. Tumour Biol 2013; 34:3049-3057. [PMID: 23765761 DOI: 10.1007/s13277-013-0870-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Accepted: 05/15/2013] [Indexed: 12/19/2022] Open
Abstract
Genetic alterations in the deleted in colorectal carcinoma (DCC) gene have been a priori reported to associate with metastasis in variety of human cancers. We investigated the association between potentially functional SNPs in DCC and susceptibility to esophageal (EC) and gastric (GC) cancers in Kashmir Valley. We genotyped two SNPs DCC rs714 (A>G) and DCC rs2229080 (C>G) of DCC in 135 EC patients, 108 GC patients, and 195 controls matched by age and sex in Kashmir Valley by polymerase chain reaction-RFLP method. Risk for developing EC and GC was estimated by binary logistic regression by using SPSS. We also performed a meta-analysis on DCC rs714 (A>G) and evaluated the association between the DCC rs714 (A>G) polymorphisms and cancer risk. A significant difference in DCC rs714 (A>G) genotype distribution between EC and GC cases and corresponding control groups was observed (odds ratio (OR) = 1.92; P = 0.03; P-trend = 0.04; false discovery rate (FDR) Pcorr = 0.03: OR = 2.15; P = 0.02; P-trend = 0.01; FDR Pcorr = 0.03). But no such association was observed in DCC rs2229080 (C>G). Further, DCC rs714 (A>G) AA genotype showed significantly increased risk for both gastric squamous cell carcinoma (OR = 5.63; P = 0.02; FDR Pcorr = 0.01) and gastric adenocarcinoma (OR = 2.15; P = 0.02; FDR Pcorr = 0.01). Smoking and salted tea are independently associated with both EC and GC, but gene-environment interaction did not further modulate the risk. Meta-analysis also suggested both independent and overall association of DCC rs714 (A>G) polymorphism with cancer (P = 0.000). In conclusion, genetic variations in DCC rs714 (A>G) modulate risk of EC and GC in high-risk Kashmir population.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India
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Meta-analysis: glutathione S-transferase T1 null allele is associated with gastric cancer risk. Tumour Biol 2013; 35:239-45. [PMID: 23975364 DOI: 10.1007/s13277-013-1029-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2013] [Accepted: 07/15/2013] [Indexed: 10/26/2022] Open
Abstract
Allelic variant within genes encoding glutathione S-transferase T1 (GSTT1) has been suggested to be a possible risk factor of gastric cancer, but previous studies provide controversial results. This study aimed to assess the effects of GSTT1 polymorphism on gastric cancer by means of meta-analysis. We included published studies on the relationship between GSTT1 null allele and gastric cancer risk after searching electronic databases. A meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95% CI). Forty-two studies with a total of 8,203 gastric cancer cases and 13,866 controls were included into this meta-analysis. When all 42 studies were pooled into this meta-analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk (OR = 1.24, 95% CI 1.14-1.36, P < 0.00001). Sensitivity analysis by excluding individual studies showed that there was no effect on the pooled OR with 95% CI. After excluding studies with low quality, there was still a significant association between the GSTT1 null allele and gastric cancer risk (OR = 1.24, 95% CI 1.13-1.36, P < 0.00001). In the subgroup analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk in both Europeans and Asians. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null allele is associated with increased risk of gastric cancer.
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Bao LD, Niu JX, Song H, Wang Y, Ma RL, Ren XH, Wu XL. Association between the GSTP1 codon 105 polymorphism and gastric cancer risk: an updated meta-analysis. Asian Pac J Cancer Prev 2013; 13:3687-93. [PMID: 23098455 DOI: 10.7314/apjcp.2012.13.8.3687] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE The current meta-analysis was performed to address a more accurate estimation of the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and risk of gastric cancer (GC), which has been widely reported with conflicting results. METHODS A comprehensive literature search was conducted to identify all the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS A total of 20 studies containing 2,821 GC cases and 6,240 controls were finally included in the analyses. Overall, no significant association between GSTP1 polymorphism and GC risk was observed in worldwide populations. However, subgroup analysis stratified by ethnicity showed that GSTP1 polymorphism was significantly associated with increased risk of GC in Asians (G vs. A, OR = 1.273, 95%CI=1.011-1.605; GG vs. AA, OR=2.103, 95%CI=1.197- 3.387; GG vs. AA+AG, OR =2.103, 95%CI=1.186-3.414). In contrast, no significant association was found in Caucasians in any genetic models, except for with AG vs. AA (OR=0.791, 95%CI=0.669-0.936). Furthermore, the GSTP1 polymorphism was found to be significantly associated with GC in patients with H. pylori infection and in those with a cardiac GC. Subgroup analysis stratified by Lauren's classification and smoking status showed no significant association with any genetic model. No studies were found to significantly influence the pooled effects in each genetic mode, and no potential publication bias was detected. CONCLUSIONS This meta-analysis suggested that the GSTP1 polymorphism might be associated with increased risk of GC in Asians, while GSTP1 heterozygote genotype seemed to be associated with reduced risk of GC. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.
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Affiliation(s)
- Li-Dao Bao
- Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot City, China
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Ma W, Zhuang L, Han B, Tang B. Association between glutathione S-transferase T1 null genotype and gastric cancer risk: a meta-analysis of 48 studies. PLoS One 2013; 8:e60833. [PMID: 23585855 PMCID: PMC3621870 DOI: 10.1371/journal.pone.0060833] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2012] [Accepted: 03/03/2013] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Glutathione S-transferases (GSTs) have proved to be involved in the detoxifying several carcinogens and may play an important role in carcinogenesis of cancer. Previous studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk reported inconclusive results. To clarify the possible association, we conducted a meta-analysis of eligible studies. METHODS We searched in the Pubmed, Embase, and Wangfang Medicine databases for studies assessing the association between GSTT1 null genotype and gastric cancer risk. The pooled odds ratio (OR) and its 95% confidence interval (95%CI) was calculated to assess the strength of the association. A total of 48 studies with a total of 24,440 individuals were ultimately eligible for meta-analysis. RESULTS Overall, GSTT1 null genotype was significantly associated with increased risk of gastric cancer (Random-effect OR = 1.23, 95%CI 1.13-1.35, P OR <0.001, I(2) = 45.5%). Significant association was also found in Caucasians, East Asians, and Indians (P Caucasians = 0.010; P East Asians = 0.003; P Indians = 0.017). After adjusting for other confounding variables, GSTT1 null genotype was also significantly associated with increased risk of gastric cancer (Random-effect OR = 1.43, 95%CI 1.20-1.71, P OR <0.001, I(2) = 48.1%). CONCLUSION The meta-analysis provides strong evidence for the significant association between GSTT1 null genotype and increased risk of gastric cancer.
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Affiliation(s)
- Weiyuan Ma
- Department of Dermatology, Qilu Hospital, Shandong University, Jinan, China
| | - Le Zhuang
- Department of Dermatology, Qilu Hospital, Shandong University, Jinan, China
| | - Bo Han
- Institute of Pathology, School of Medicine, Shandong University, Jinan, China
| | - Bo Tang
- Department of Oncology, Southwest Hospital, the Third Military Medical University, Chongqing, China
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Zhang W, Huang J, Peng G, Ding Q, Chen J, Hua Y, Xue J. Null genotype of glutathione S-transferase T1 contributes to increased risk of gastric cancer in Asian population. Tumour Biol 2013; 34:1461-6. [PMID: 23397542 DOI: 10.1007/s13277-013-0669-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Accepted: 01/15/2013] [Indexed: 12/11/2022] Open
Abstract
Numerous studies were published to investigate the relationship between the glutathione S-transferase T1 (GSTT1) null genotype and risk of gastric cancer in Asians, but the conclusions from those studies were conflicting. To get a more precise estimation on the possible association, we performed a meta-analysis of published data. A comprehensive literature was conducted and 27 case-control studies with 14,905 individuals were finally included, involving a total of 6,270 cases and 8,635 controls. The strength of the association between GSTT1 polymorphism and gastric cancer risk was estimated by calculating the pooled odds ratio with its 95 % confidence interval (95 % CI). A meta-analysis of total 27 studies showed that GSTT1 null genotype was obviously associated with increased risk of gastric cancer in Asians (random effect odds ratio (OR) =1.29, 95 % CI 1.16-1.44, P OR<0.001). A subgroup analysis of 14 studies with large sample size also showed an obvious association between GSTT1 null genotype and increased risk of gastric cancer in Asians (fixed effect OR=1.14, 95 % CI 1.06-1.23, P OR=0.001). In conclusion, the meta-analysis suggests that null genotype of GSTT1 contributes to increased risk of gastric cancer in Asian population.
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Affiliation(s)
- Wanli Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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CYP2E1 RsaI/PstI polymorphism and gastric cancer susceptibility: meta-analyses based on 24 case-control studies. PLoS One 2012; 7:e48265. [PMID: 23139769 PMCID: PMC3489680 DOI: 10.1371/journal.pone.0048265] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 09/21/2012] [Indexed: 02/07/2023] Open
Abstract
Background Previous reports implicate CYP2E1 RsaI/PstI polymorphism as a possible risk factor for several cancers. Published studies on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to gastric cancer are controversial. This study aimed to determine this relationship accurately. Methods Meta-analyses that assessed the association of CYP2E1 RsaI/PstI variations with gastric cancer were conducted. Subgroup analyses on ethnicity, smoking status, alcohol consumption, and source of controls were also performed. Eligible studies up to Mar 2012 were identified. Results After rigorous searching and screening, 24 case-control studies comprising 3022 cases and 4635 controls were selected for analysis. The overall data failed to indicate the significant associations of CYP2E1 RsaI/PstI polymorphisms with the gastric cancer risk [c2 vs. c1: odds ratio (OR) = 1.06; 95% confidence interval (CI) = 0.88–1.28; c2c2 vs. c1c1: OR = 1.23; 95% CI = 0.78–1.92; c2c2+c1c2 vs. c1c1: OR = 0.93; 95% CI = 0.79–1.10]. Similar results were observed in the subgroup analyses on ethnicity, drinking status, and source of controls. However, in the subgroup analysis on smoking status, a borderline increase in cancer risk was found among long-term smokers (c2c2+c1c2 vs. c1c1: OR = 1.39; 95% CI = 1.00–1.92). Conclusion CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to gastric cancer among individuals who have a smoking history. Large and well-designed studies are needed to confirm this conclusion.
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García-González MA, Quintero E, Bujanda L, Nicolás D, Benito R, Strunk M, Santolaria S, Sopeña F, Badía M, Hijona E, Pérez-Aísa MA, Méndez-Sánchez IM, Thomson C, Carrera P, Piazuelo E, Jiménez P, Espinel J, Campo R, Manzano M, Geijo F, Pellisé M, González-Huix F, Espinós J, Titó L, Zaballa M, Pazo R, Lanas A. Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype. Mutagenesis 2012; 27:771-777. [PMID: 22952149 DOI: 10.1093/mutage/ges049] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups. Our goal was to perform a nationwide, case-control study in Spain to evaluate the relevance of several functional GST gene polymorphisms and environmental factors to GC risk and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis identified Helicobacter pylori infection with CagA strains [odds ratio (OR): 2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI: 1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1: 21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1 null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC patients and controls. Subgroup analysis for age, gender, Helicobacter pylori status, smoking habits, family history of GC, anatomic location and histological subtype revealed no significant association between GST variants and GC risk. Our results show that the GST polymorphisms evaluated in this study are not relevant when determining the individual susceptibility to GC or phenotype in a South-European population.
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Malik MA, Zargar SA, Mittal B. Role of NQO1 609C>T and NQO2 -3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis. Mol Biol Rep 2012; 39:9095-9104. [PMID: 22736108 DOI: 10.1007/s11033-012-1781-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Accepted: 06/09/2012] [Indexed: 01/01/2023]
Abstract
Esophageal cancer (EC) is a complex multifactorial disorder, where environmental and genetic factors play major role. NADPH:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are phase II cytosolic enzymes that catalyze metabolism of quinones, important in the detoxification of environmental carcinogens. A case-control study was performed to investigated the associations of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to EC in a high-risk Kashmiri population of India in 135 EC patients and 195 unrelated healthy controls using PCR-RFLP. We also performed a meta analysis of nine published studies (1,224 cases and 1,740 controls) on NQO1 609C>T and evaluated the association between the NQO1 609C>T polymorphisms and esophageal cancer risk. A significant difference in NQO1 609C>T and NQO2 -3423G>A genotype distribution between EC cases and corresponding controls groups was observed (OR = 2.65; 95 % CI = 1.29-5.42 and OR = 1.88; 95 % CI = 1.02-3.49 respectively). Further, gene-gene interaction showed significantly increased risk for esophageal adenocarcinoma with variant genotypes of NQO1 609C>T and NQO2 -3423G>A polymorphisms and interaction with environmental risk factors revealed pronounced risk of EC with NQO1 609C>T TT genotype in high salted tea users of Kashmir valley (OR = 3.72, 95 % CI = 0.98-14.19). Meta analysis of NQO 609C>T polymorphism also suggested association of the polymorphism with EC in Asians as well as Europeans. In conclusion, NQO1 609C>T and NQO2 -3423G>A genetic variations modulate risk of EC in high-risk Kashmir population.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow 226014, India
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Dong H, Jin X, Hu J, Li H, He X, Liu X, Bao G. High γ-radiation sensitivity is associated with increased gastric cancer risk in a Chinese Han population: a case-control analysis. PLoS One 2012; 7:e43625. [PMID: 22928006 PMCID: PMC3425539 DOI: 10.1371/journal.pone.0043625] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2012] [Accepted: 07/25/2012] [Indexed: 01/12/2023] Open
Abstract
Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of several malignancies, but not including gastric cancer. In this case-control study, radiation sensitivity as measured by chromatid breaks per cell (b/c) was examined in cultured peripheral blood lymphocytes (PBLs) from 517 patients with gastric cancer and 525 healthy controls. Our results showed that b/c values were significantly higher in cases than in controls (Mean [SD], 0.47 [0.20] vs. 0.34 [0.17]; P<0.001). Using the 50th percentile value for controls (0.34 b/c) as the cutoff point, unconditional logistic regression analysis revealed that γ–radiation-sensitive individuals were at significantly higher risk for gastric cancer (adjusted odds ratio [OR] 2.01, 95% confidence interval [CI] 1.49–3.13). Quartile stratification analysis indicated a dose-response relationship between γ-radiation sensitivity and gastric cancer risk (P for trend <0.001). When using the subjects in first quartile of b/c values as reference, the adjusted ORs and corresponding CIs for the subjects in second, third, and fourth quartiles were 1.48 (0.91–2.17), 2.42 (1.76–3.64), and 3.40 (2.11–5.29), respectively. The γ-radiation sensitivity was related to age and smoking status. In addition, a clear joint effect on cancer risk was found between γ-Radiation sensitivity and smoking status. The risk for ever smokers with high sensitivity was higher than those for never smokers with high sensitivity and ever smokers with low sensitivity (OR [CI], 4.67 [2.31–6.07] vs. 2.14 [1.40–3.06] vs. 2.42 [1.57–3.95], respectively). No significant interaction was found between both factors (P for interaction = 0.42). We conclude that chromatid radiosensitivity is associated with gastric cancer susceptibility in a Chinese population.
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Affiliation(s)
- Honglin Dong
- Department of General Surgery, Second Hospital, Shanxi Medical University. Taiyuan, China
| | - Xiaowei Jin
- Department of Digestive Diseases, General Hospital of Air Forces of PLA, Beijing, China
| | - Jie Hu
- Department of General Surgery, Second Hospital, Shanxi Medical University. Taiyuan, China
| | - Haifeng Li
- Department of General Surgery, Second Hospital, Shanxi Medical University. Taiyuan, China
| | - Xianli He
- Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China
| | - Xiaonan Liu
- Xijing Hospital of Digestive Disease, The Fourth Military Medical University, Xi'an, China
- * E-mail: (XL); (GB)
| | - Guoqiang Bao
- Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China
- * E-mail: (XL); (GB)
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Han F, Wang X, Wang X, Luo Y, Li W. Meta-analysis of the association of CYP1A1 polymorphisms with gastric cancer susceptibility and interaction with tobacco smoking. Mol Biol Rep 2012; 39:8335-44. [PMID: 22707145 DOI: 10.1007/s11033-012-1683-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 06/05/2012] [Indexed: 12/29/2022]
Abstract
The association of two cytochrome P4501A1 (CYP1A1) polymorphisms, m1 (T6235C transition) and m2 (A4889G transition), with gastric cancer risk is inconclusive. We conducted a meta-analysis of all available studies to evaluate the potential role of the polymorphisms and their interactions with tobacco smoking in gastric cancer susceptibility. Published literature from PubMed was retrieved by two investigators independently. Fourteen case-control studies with 2,032 gastric cancer cases and 5,099 controls were selected. A fixed effects model or a random-effects model was used to estimate the odds ratio (OR) for the CYP1A1 polymorphisms and the occurrence of gastric cancer. Significant associations between CYP1A1 m1 and m2 polymorphisms and gastric cancer susceptibility were not observed in all genetic models in the overall analyses. Subgroup analyses by ethnicity and source of controls did not reveal significant associations with gastric cancer risk. Stratification analysis by smoking status found that carriers of the heterozygous and homozygous m1 genotypes decreased the susceptibility of gastric cancer among ever-smokers (pooled OR = 0.56, 95 % CI 0.36-0.89, fixed effects). In contrast, the m2 genotypes (G/G and A/G) did not show any relevance to gastric cancer risk among the smoking population (pooled OR = 1.30, 95 % CI 0.84-2.00, fixed effects). Overall, we found that the CYP1A1 polymorphism itself, either m1 or m2, did not represent an independent genetic risk factor influencing gastric cancer. However, subgroup analyses suggest that carriers of the heterozygous and homozygous m1 genotype who are exposed to tobacco smoke have a significantly lower risk of developing gastric cancer. To explain the observed reduction of gastric cancer risk, we proposed a novel hypothesis of "observation bias". This hypothesis is also applicable to explain the combined effects of other genetic polymorphisms and environmental factors on the risk of developing cancers, and the rationality of the hypothesis needs to be further investigated.
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Affiliation(s)
- Fujun Han
- Cancer Center, The First Hospital of Jilin University, Changchun 130021, China
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Quantitative assessment of the associations between CYP1A1 polymorphisms and gastric cancer risk. Tumour Biol 2012; 33:1125-32. [PMID: 22359202 DOI: 10.1007/s13277-012-0353-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Accepted: 02/08/2012] [Indexed: 01/12/2023] Open
Abstract
A great number of studies regarding the association between MspI and Ile462Val polymorphisms in the CYP1A1 gene and gastric cancer have been published. However, the results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. Published literature from PubMed, ISI Web of Science and other Chinese databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random or fixed effect model. Nine studies (860 cases/2183 controls) for CYP1A1 MspI polymorphism and nine studies (1161 cases/3273 controls) for CYP1A1 Ile462Val polymorphism were included in this meta-analysis. MspI polymorphism was not associated with gastric cancer risk (dominant model, OR = 0.95, 95%CI 0.80-1.14; recessive model, OR = 1.01, 95%CI 0.76-1.35; CC vs. TT, OR = 1.03, 95%CI 0.76-1.41; TC vs. TT, OR = 0.95, 95%CI 0.78-1.15). Similarly, there was no association between Ile462Val polymorphism and gastric cancer risk (dominant model, OR = 0.93, 95%CI 0.79-1.10; recessive model, OR = 1.34, 95%CI 0.90-2.00; GG vs. AA, OR = 1.27, 95%CI 0.84-1.90; AG vs. AA, OR = 0.87, 95%CI 0.71-1.07). In the subgroup analysis, no significant association was found in ever smokers, never smokers, Asians and Caucasians. This meta-analysis suggested that there were no associations between CYP1A1 polymorphisms and gastric cancer.
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Feng J, Pan X, Yu J, Chen Z, Xu H, El-Rifai W, Zhang G, Xu Z. Functional PstI/RsaI polymorphism in CYP2E1 is associated with the development, progression and poor outcome of gastric cancer. PLoS One 2012; 7:e44478. [PMID: 22957075 PMCID: PMC3434136 DOI: 10.1371/journal.pone.0044478] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Accepted: 08/07/2012] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Cytochrome P450 2E1 (CYP2E1), an ethanol-inducible enzyme, has been shown to metabolically activate various carcinogens, which is critical for the development and progression of cancers. It has demonstrated that CYP2E1 polymorphisms alter the transcriptional activity of the gene. However, studies on the association between CYP2E1 polymorphisms (PstI/RsaI or DraI) and gastric cancer have reported conflicting results. Thus, the aim of the present study was to investigate whether CYP2E1 polymorphisms is associated with the development and progression of gastric cancer and its prognosis in Chinese patients. METHODS A case-control study was conducted in which CYP2E1 PstI/RsaI and DraI polymorphisms were analyzed in 510 Chinese patients with gastric cancer and 510 age- and sex- matched healthy controls by PCR-RFLP. Odds ratios were estimated by multivariate logistic regression, and the lifetime was calculated by Kaplan-Meier survival curves. In addition, a meta-analysis was also conducted to verify the findings. RESULTS For CYP2E1 PstI/RsaI polymorphism, C2C2 homozygotes (OR = 2.15; CI: 1.18-3.94) and C2 carriers (OR = 1.48; CI: 1.13-1.96) were associated with an increased risk of gastric cancer when compared with C1C1 homozygotes. Both C1C2 and C2C2 genotypes were associated with advanced stage, but not the grade of gastric cancer. Moreover, C2C2 genotype was identified as an independent marker of poor overall survival for gastric cancer. However, there was not any significant association between CYP2E1 DraI polymorphism and the risk of gastric cancer. In the meta-analysis, pooled data from 13 studies confirmed that the CYP2E1 PstI/RsaI polymorphism was associated with a significantly increased risk of gastric cancer. CONCLUSION CYP2E1 PstI/RsaI polymorphism is associated with increased risk of development, progression and poor prognosis of gastric cancer in Chinese patients. Pooled data from 13 studies, mainly in Asian countries, are in agreement with our findings.
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Affiliation(s)
- Jin Feng
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaolin Pan
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Junbo Yu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zheng Chen
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wael El-Rifai
- Department of Surgery, Cancer Biology, and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - Guoxin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- * E-mail: (ZX); (GZ)
| | - Zekuan Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- * E-mail: (ZX); (GZ)
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Malik MA, Sharma KL, Zargar SA, Mittal B. Association of matrix metalloproteinase-7 (-181A>G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley. Saudi J Gastroenterol 2011; 17:301-306. [PMID: 21912055 PMCID: PMC3178916 DOI: 10.4103/1319-3767.84480] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2010] [Accepted: 02/11/2011] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND/AIM Degradation of the basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with a broad substrate specificity, and its expression has been shown to be associated with tumor invasion and metastasis for various cancers. PATIENTS AND METHODS To document the role of MMP-7 polymorphism in esophageal carcinogenesis, a case-control study was performed comprising 135 patients with esophageal cancer (EC) and 195 healthy controls. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data were statistically analyzed using χ2 - test and logistic regression models. RESULTS Carriers for the MMP-7 (-181A>G) GG were associated with an increased risk for EC [odds ratio (OR = 2.17; 95% confidence interval (CI) = 1.21-3.92; P = 0.010; P-trend = 0.04]. Also, in a recessive model, our results showed that MMP-7 (-181A>G) GG allele conferred significantly higher risk for EC (OR =2.16; 95% CI = 1.31-3.54; P = 0.003). The high risk due to MMP-7 (-181GG) genotype was limited to squamous cell histology of EC (OR = 2.41; 95% CI = 1.27-4.56; P = 0.007). Although smoking (Hukka) and high consumption of salted tea are independent risk factors for EC, the interaction of MMP-7 (-181A>G) genotypes with these factors did not further modulate the risk of EC. CONCLUSIONS In conclusion, our results show that MMP-7 (-181A>G) GG carriers are at a higher risk of esophageal squamous cell carcinoma in Kashmir valley.
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Affiliation(s)
- Manzoor A. Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
| | - Kiran L. Sharma
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
| | - Showket A. Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, India
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Shukla RK, Kant S, Bhattacharya S, Mittal B. Association of genetic polymorphism of GSTT1, GSTM1 and GSTM3 in COPD patients in a north Indian population. COPD 2011; 8:167-172. [PMID: 21513434 DOI: 10.3109/15412555.2011.560128] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Environmental exposures and genetic susceptibility can contribute to lung function decline in chronic obstructive pulmonary disease (COPD). Cigarette smoking is the main etiological factor for decline in lung function in COPD. However, only 10-20% chronic smokers develop symptomatic COPD. Genetic susceptibility to COPD might depend upon the variation of enzyme activities that detoxify cigarette smoke components. We performed a case control study to assess the association of Glutathione- S-transferase T1(GSTT1),Glutathione- S-transferase M1 (GSTM1), and Glutathione-S-transferase M3(GSTM3) common polymorphisms with the susceptibility to COPD patient in a north India population. In the present study, the genotypes of 412 subjects, (204 COPD patients and 208 healthy controls) were analyzed. Statistical analysis revealed that the frequency of homozygous GSTM1 null genotype was found to be significant higher in COPD patients as compared with healthy controls (OR, 2.58; 95% CI, 1.73-3.84; P = 0.001), but there were no significant differences in the distribution of homozygous null GSTT1 and 3-bp deletion polymorphism (rs1799735) in intron 6 variant allele in GSTM3 between COPD patients and healthy controls. Our study results suggest that GSTM1 null polymorphism is associated with genetic susceptibility to COPD. Moreover, we also found association between this polymorphism with pulmonary function test in smokers as well as nonsmokers.
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Affiliation(s)
- Rajni K Shukla
- Department of Pulmonary Medicine, Chhatrapati Shahuji Maharaj Medical University Erstwhile King George Medical College, Lucknow, 226003, India
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The association between GSTM1 polymorphism and gastric cancer risk: a meta-analysis. Mol Biol Rep 2011; 39:685-91. [PMID: 21553222 DOI: 10.1007/s11033-011-0786-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2010] [Accepted: 04/29/2011] [Indexed: 12/23/2022]
Abstract
Relationship of gastric cancer with the GSTM1 polymorphism was reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between GSTM1 polymorphism and gastric cancer susceptibility. Relevant studies were identified from PubMed and references of retrieved articles. A meta-analysis was performed, which included 38 studies with 6,605 gastric cancer cases and 11,311 controls. The combined result based on all studies showed there was a significant link between GSTM1 null genotype and gastric cancer (OR=1.20, 95%CI: 1.08-1.34). When stratifying for the race, the phenomenon was found that gastric cancer case had a significantly higher frequency of GSTM1 null genotype than control in Asians (OR=1.27, 95%CI: 1.10-1.47). However, there was not enough evidence to show there was a significant difference in GSTM1 null genotype distribution between gastric cancer case and control in Caucasians (OR=1.13, 95%CI: 0.96-1.32). This meta-analysis indicated that GSTM1 null genotype might be associated with increased gastric cancer risk in Asians. However, this meta-analysis did not provide an evidence of confirming association between GSTM1 polymorphism and gastric cancer in Caucasians.
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Zhang X, Zhong R, Zhang Z, Yuan J, Liu L, Wang Y, Kadlubar S, Feng F, Miao X. Interaction of cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer. Mol Carcinog 2011; 50:876-83. [PMID: 21538574 DOI: 10.1002/mc.20784] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2011] [Revised: 03/24/2011] [Accepted: 03/27/2011] [Indexed: 12/23/2022]
Abstract
Overexpression of cyclooxygenase (COX)-2 has been implicated in the development of cancer. This study aimed to evaluate the relationship between genetic variants in COX-2 promoter interacting with Helicobacter pylori and the susceptibility to gastric cancer (GC). Three COX-2 polymorphisms -1290A>G (rs689465), -1195G>A (rs689466), and -765G>C (rs20417) were genotyped in 323 GC patients and 944 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. In GC patients, the ORs were 2.33 (95% CI = 1.50-3.63) and 2.70 (95% CI = 1.68-4.33) for -1195AA and -765CG genotype carriers, respectively. Haplotype analysis showed all -1195A allele-containing haplotypes, except G(-1290)-A(-1195)-G(-765), were associated with increased risk for GC, compared with the A(-1290)-G(-1195)-G(-765) haplotype. Moreover, significant multiplicative and additive interactions were observed between H. pylori infection and all these three polymorphisms, and H. pylori-infected subjects carrying the variant allele of -1290A>G, -1195G>A, or -765G>C had increased risk of GC compared with non-H. pylori-infected subjects with wild-type allele (OR = 4.10, 95% CI = 1.90-8.83; OR = 3.46, 95% CI = 1.31-9.11; and OR = 3.32, 95% = 1.27-8.73, respectively). Our results suggested that the COX-2 promoter polymorphisms were associated with increased risk of GC, especially interacting with H. pylori infection.
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Affiliation(s)
- Xuemei Zhang
- Department of Molecular biology, College of Life Sciences, Hebei United University, Tangshan, China
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Malik MA, Zargar SA, Mittal B. Role of NQO1 609C>T and NQO2-3423G>A polymorphisms in susceptibility to gastric cancer in Kashmir valley. DNA Cell Biol 2011; 30:297-303. [PMID: 21294640 DOI: 10.1089/dna.2010.1115] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
NADPH: quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside: quinone oxidoreductase 2 (NQO2) are cytosolic enzymes that catalyze reductive activation of carcinogens from cigarette smoke, such as nitrosamines and heterocyclic amines. These enzymes also protect cells against oxidative damage from reactive oxygen species. The present study investigated the associations of genetic variants of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to gastric cancer (GC) as well as their interactions with known risk factors in Kashmir valley. A case control study was performed in 303 subjects (108 GC and 195 healthy controls). All subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed by chi-square test and logistic regression model. The NQO1 609C>T TT genotype and T allele were significantly associated with increased risk for GC, whereas NQO2 -3423G>A polymorphism did not show any association with GC. Also, NQO1 609C>T TT genotype showed significant association with gastric adenocarcinoma. The interaction of NQO1/NQO2 genotypes with high consumption of salted tea, a known risk factor, did not further modulate the risk of GC. In conclusion, NQO1 609C>T polymorphism shows association with GC risk in Kashmir valley.
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Affiliation(s)
- Manzoor Ahmad Malik
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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Dikshit RP, Mathur G, Mhatre S, Yeole BB. Epidemiological review of gastric cancer in India. Indian J Med Paediatr Oncol 2011; 32:3-11. [PMID: 21731209 PMCID: PMC3124986 DOI: 10.4103/0971-5851.81883] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Stomach cancer is the one of the leading cause of cancer in southern region of India. Its incidence is decreasing worldwide yet on global scale stomach cancer remains one of the most common causes of cancer death. Etiology of gastric cancer includes Helicobacter pylori infection, diet and lifestyle, tobacco, alcohol and genetic susceptibility. In this review, we tried to find the contribution of Indian scientist in understanding the descriptive and observational epidemiology of stomach cancer. PubMed was used as a search platform using key words such as "stomach cancer, treatment, clinical characteristics, stomach cancer outcome, epidemiology, etiological factor and their corresponding Mesh terms were used in combination with Boolean operators OR, AND". Most of the reported studies on gastric cancer from India are case report or case series and few are case-control studies. Indian studies on this topic are limited and have observed H. pylori infection, salted tea, pickled food, rice intake, spicy food, soda (additive of food), tobacco and alcohol as risk factors for gastric cancer. More research is required to understand the etiology, develop suitable screening test, to demarcate high-risk population and to develop and evaluate the effect of primary prevention programs.
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Affiliation(s)
| | - Garima Mathur
- Department of Epidemiology, Tata Memorial Hospital, Mumbai, India
| | - Sharayu Mhatre
- Department of Epidemiology, Tata Memorial Hospital, Mumbai, India
| | - B. B. Yeole
- Population Based Cancer Registry, Indian Cancer Society, Mumbai, Maharashtra, India
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Yadav DS, Devi TR, Ihsan R, Mishra AK, Kaushal M, Chauhan PS, Bagadi SAR, Sharma J, Zamoawia E, Verma Y, Nandkumar A, Saxena S, Kapur S. Polymorphisms of glutathione-S-transferase genes and the risk of aerodigestive tract cancers in the Northeast Indian population. Genet Test Mol Biomarkers 2010; 14:715-23. [PMID: 20854097 DOI: 10.1089/gtmb.2010.0087] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Widespread use of tobacco and betel quid consumption and a high incidence of tobacco-associated aerodigestive tract cancers have been reported in different ethnic groups from several regions of Northeast (NE) India. This study was done to explore the possibility of phase II metabolic enzymes being responsible for the high prevalence of cancers in this region of India. METHODS Samples from 370 cases with oral, gastric, and lung cancers and 270 controls were analyzed for polymorphism of glutathione-S-transferase (GST) genes using polymerase chain reaction-restriction fragment length polymorphism-based methods. RESULTS AND CONCLUSIONS Tobacco smoking and betel quid chewing were found to be high risk factors for oral and lung cancers but not for gastric cancer, whereas tobacco chewing was found to be a risk factor for oral cancer but not for gastric or lung cancer. The variant genotypes of GSTP1 were not associated with any of the aerodigestive tract cancers. GSTT1 and GSTM1 null genotypes appeared to play a protective role for lung cancer (odds ratio [OR] = 0.47, 95% confidence interval [95% CI]: 0.24-0.93, p = 0.03) and (OR = 0.52, 95% CI: 0.28-0.96, p = 0.04), but they were not associated with oral and gastric cancers. However, when data was analyzed in different geographic regions the GSTT1 null genotype was found to be a significant risk factor for oral (OR = 2.58, 95% CI 1.01-6.61, p = 0.05) as well as gastric cancer (OR = 3.08, 95% CI 1.32-7.19, p = 0.009) in samples obtained from the Assam region of NE India. This is the first study on the association of GST polymorphisms and aerodigestive tract cancers in the high-risk region of NE India.
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Di Pietro G, Magno LAV, Rios-Santos F. Glutathione S-transferases: an overview in cancer research. Expert Opin Drug Metab Toxicol 2010; 6:153-70. [PMID: 20078251 DOI: 10.1517/17425250903427980] [Citation(s) in RCA: 155] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
IMPORTANCE OF THE FIELD The Glutathione S-transferases (GSTs) have advanced beyond the classic view of their role in metabolism and are encouraging scientists to assess new approaches to cancer risk characterization and chemotherapy resistance and are opening up exciting possibilities in drug discovery. AREAS COVERED IN THIS REVIEW In this review, the most recent knowledge about the impact of GST genetic polymorphisms in human's cancer susceptibility, ethnic differences in the effects of risk factors and the rise of the GSTs as important targets for drug development are presented. In this context, the ethnic distribution of GST alleles in different populations, which is an important concept that is being incorporated in epidemiologic studies of cancer risk and environmental exposure, was also evaluated. We present up-to-date information about the new generation of GST-activated cytotoxic prodrugs based on GST overexpression in tumor-acquired drug resistance and the newest results of clinical trials. WHAT THE READER WILL GAIN A critical approach of the major advances in research of GST, underlining the new advances of GST genes polymorphisms in cancer susceptibility and target for therapeutic intervention. TAKE HOME MESSAGE Although polygenic factors are involved in increased risk of cancer, the interindividual GST variability plays a central role in reduce cells exposure to carcinogens.
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Affiliation(s)
- Giuliano Di Pietro
- Universidade Estadual de Santa Cruz, Departamento de Ciências da Saúde, Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM), Ilhéus, Bahia 45662-900, Brazil.
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Lonergan KM, Chari R, Coe BP, Wilson IM, Tsao MS, Ng RT, MacAulay C, Lam S, Lam WL. Transcriptome profiles of carcinoma-in-situ and invasive non-small cell lung cancer as revealed by SAGE. PLoS One 2010; 5:e9162. [PMID: 20161782 PMCID: PMC2820080 DOI: 10.1371/journal.pone.0009162] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2009] [Accepted: 01/07/2010] [Indexed: 12/29/2022] Open
Abstract
Background Non-small cell lung cancer (NSCLC) presents as a progressive disease spanning precancerous, preinvasive, locally invasive, and metastatic lesions. Identification of biological pathways reflective of these progressive stages, and aberrantly expressed genes associated with these pathways, would conceivably enhance therapeutic approaches to this devastating disease. Methodology/Principal Findings Through the construction and analysis of SAGE libraries, we have determined transcriptome profiles for preinvasive carcinoma-in-situ (CIS) and invasive squamous cell carcinoma (SCC) of the lung, and compared these with expression profiles generated from both bronchial epithelium, and precancerous metaplastic and dysplastic lesions using Ingenuity Pathway Analysis. Expression of genes associated with epidermal development, and loss of expression of genes associated with mucociliary biology, are predominant features of CIS, largely shared with precancerous lesions. Additionally, expression of genes associated with xenobiotic metabolism/detoxification is a notable feature of CIS, and is largely maintained in invasive cancer. Genes related to tissue fibrosis and acute phase immune response are characteristic of the invasive SCC phenotype. Moreover, the data presented here suggests that tissue remodeling/fibrosis is initiated at the early stages of CIS. Additionally, this study indicates that alteration in copy-number status represents a plausible mechanism for differential gene expression in CIS and invasive SCC. Conclusions/Significance This study is the first report of large-scale expression profiling of CIS of the lung. Unbiased expression profiling of these preinvasive and invasive lesions provides a platform for further investigations into the molecular genetic events relevant to early stages of squamous NSCLC development. Additionally, up-regulated genes detected at extreme differences between CIS and invasive cancer may have potential to serve as biomarkers for early detection.
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Affiliation(s)
- Kim M. Lonergan
- Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
- * E-mail:
| | - Raj Chari
- Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Bradley P. Coe
- Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Ian M. Wilson
- Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Ming-Sound Tsao
- Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada
| | - Raymond T. Ng
- Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
- Computer Science, University of British Columbia, Vancouver, British Columbia, Canada
| | - Calum MacAulay
- Imaging Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Stephen Lam
- Imaging Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Wan L. Lam
- Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
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