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Sheehan BJ, Edwards B, Medrano IS, El-Saidi MA, Zaidan WR, El-Ezzi AA, Kuddus RH. Association between two single nucleotide polymorphisms of the Prostaglandin-Endoperoxide Synthase 1 and 2 genes and cell proliferative prostatic diseases in Lebanon. Oncotarget 2025; 16:262-272. [PMID: 40184332 PMCID: PMC11970937 DOI: 10.18632/oncotarget.28710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 03/13/2025] [Indexed: 04/06/2025] Open
Abstract
The polymorphic genes PTGS1 and PTGS2 encode cyclooxygenases COX-1 and COX-2, respectively. Overexpression of these cyclooxygenases is linked to inflammation and neoplasms. This study investigated the potential association between the single nucleotide polymorphism (SNP) -842A>G (rs10306114) of the PTGS1 gene and SNP-765G>C (rs20417) of the PTGS2 gene with prostate cancer (PCa) and benign prostate hyperplasia (BPH). Blood leucocyte DNA from 56 healthy individuals, 61 individuals with PCa, and 51 individuals with BPH were genotyped using the PCR-RFLP method. Associations were inferred by calculating odds ratios (OR) and relative risks (RR) of genotype distributions and allele frequencies. The genotypes for both SNPs were in Hardy-Weinberg equilibrium for all groups. No significant association was observed between the A or G alleles or the AA, AG, or GG genotypes of the SNP-842A>G of the PTGS1 gene and prostatic diseases. However, the C allele of SNP-765G>C of the PTGS2 gene was significantly associated with an increased risk of BPH (OR = 2.30, p-value = 0.01). Differences in the ratios of GG/GC and GG/(GC+CC) genotypes also suggested a potential association between the C allele and PCa (p-value <0.1), and the combined affected (PCa+BPH) group (p-value <0.04). The small sample size and sampling from one ethnic group are limitations of this study.
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Affiliation(s)
- Brock J. Sheehan
- Department of Biology, Utah Valley University, Orem, UT 84058, USA
| | - Bryson Edwards
- Department of Biology, Utah Valley University, Orem, UT 84058, USA
| | | | - Mohammed A. El-Saidi
- Department of Strategic Management and Operations, Utah Valley University, Orem, UT 84058, USA
| | - Wissam R. Zaidan
- Radioimmunoassay Laboratory, Lebanese Atomic Energy Commission, Beirut, Lebanon
| | - Asmahan A. El-Ezzi
- Radioimmunoassay Laboratory, Lebanese Atomic Energy Commission, Beirut, Lebanon
- Department of Chemistry and Biochemistry, Lebanese University, Hadath, Lebanon
| | - Ruhul H. Kuddus
- Department of Biology, Utah Valley University, Orem, UT 84058, USA
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Wu T, Zhang H, Jin Y, Zhang M, Zhao Q, Li H, Wang S, Lu Y, Chen S, Du H, Liu T, Guo W, Liu W. The active components and potential mechanisms of Wuji Wan in the treatment of ethanol-induced gastric ulcer: An integrated metabolomics, network pharmacology and experimental validation. JOURNAL OF ETHNOPHARMACOLOGY 2024; 326:117901. [PMID: 38341112 DOI: 10.1016/j.jep.2024.117901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 02/04/2024] [Accepted: 02/08/2024] [Indexed: 02/12/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Wuji Wan (WJW) is a traditional Chinese medicine formula that can be found in the "Prescriptions of Taiping Benevolent Dispensary" that has been employed in treating gastric discomfort, burning epigastric pain, and gastric reflux for hundreds of years and has shown promise for treating gastric ulcers (GUs). However, the active components and mechanism of action against GUs remain unclear. AIM OF THE STUDY The aim of this study was to explore the active components of WJW and elucidate the underlying mechanism involved in treating GUs. MATERIALS AND METHODS Initially, cell viability was measured by a cell counting kit 8 (CCK-8) assay to evaluate the efficacy of WJW-containing serum in vitro. The gastric ulcer index, ulcer inhibition rate, hematoxylin and staining (H&E), and periodic acid-Schiff (PAS) staining were used to evaluate the therapeutic effect of WJW in vivo. Subsequently, the levels of inflammatory factors and oxidative stress factors were determined using an enzyme-linked immunosorbent assays (ELISA) on in vitro and in vivo samples. Additionally, UPLC-Q Exactive Plus Orbitrap HRMS was used to analyze the components that were absorbed into the blood of WJW and its metabolites. Network pharmacology and metabolomics were subsequently used to identify the targets and pathways. Real-time quantitative PCR (RT‒qPCR) and Western blotting were used to verify the mRNA and protein levels of the key targets and pathways. Finally, the active components were identified by molecular docking to verify the binding stability of the components and key targets. RESULTS WJW-containing serum ameliorated ethanol-induced damage in GES-1 cells and promoted cell healing. WJW-containing serum reduced IL-6, TNF-α, MDA, and LDH levels while increasing IL-10, SOD, and T-AOC levels in the cells. Moreover, WJW treatment resulted in decreased IL-6, TNF-α, and MDA levels and increased IL-10, SOD, PGE2, and NO levels in GUs rats. In addition, eight components of WJW were absorbed into the blood. The network pharmacology results revealed 192 common targets for blood entry components and GUs, and KEGG analysis revealed that apoptosis signaling pathways were the main pathways involved in WJW activity against GUs. Metabolomic screening was used to identify 13 differential metabolites. There were 23 common targets for blood entry components, GUs, and differential metabolites, with the key targets TNF (TNF-α), AKT1, PTGS2 (COX2) and MAPK1. WJW significantly inhibited the expression of Bax, Caspase-9, Caspase-3, cleaved Caspase-9, cleaved Caspase-3, TNF-α, COX2, and p-p44/42 MAPK while promoting the expression of Bcl-2 and p-AKT1. Molecular docking revealed that the active components of WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. CONCLUSIONS WJW treatment reduces inflammation and oxidative stress injury and inhibits apoptosis signaling pathways. The main active components are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. In this paper, we provide a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms.
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Affiliation(s)
- Tiantai Wu
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550004, China
| | - Huan Zhang
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Yang Jin
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Ming Zhang
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550004, China; Natural Products Research Center of Guizhou Province, Guiyang, 550014, China
| | - Qing Zhao
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Herong Li
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Shouli Wang
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Yuan Lu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Shuaishuai Chen
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Huakang Du
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Ting Liu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Weiyu Guo
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Wen Liu
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550004, China; School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China.
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Li C, Wen R, Liu D, Yan L, Gong Q, Yu H. Assessment of the Potential of Sarcandra glabra (Thunb.) Nakai. in Treating Ethanol-Induced Gastric Ulcer in Rats Based on Metabolomics and Network Analysis. Front Pharmacol 2022; 13:810344. [PMID: 35903344 PMCID: PMC9315220 DOI: 10.3389/fphar.2022.810344] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 06/22/2022] [Indexed: 11/29/2022] Open
Abstract
Gastric ulcer (GU) is one of the most commonly diagnosed diseases worldwide, threatening human health and seriously affecting quality of life. Reports have shown that the Chinese herbal medicine Sarcandra glabra (Thunb.) Nakai (SGN) can treat GU. However, its pharmacological effects deserve further validation; in addition, its mechanism of action is unclear. An acute gastric ulcer (AGU) rat model induced by alcohol was used to evaluate the gastroprotective effect of SGN by analysis of the histopathological changes in stomach tissue and related cytokine levels; the potential mechanisms of action of SGN were investigated via serum metabolomics and network pharmacology. Differential metabolites of rat serum were identified by metabolomics and the metabolic pathways of the identified metabolites were enriched via MetaboAnalyst. Furthermore, the critical ingredients and candidate targets of SGN anti-AGU were elucidated. A compound-reaction-enzyme-gene network was established using Cytoscape version 3.8.2 based on integrated analysis of metabolomics and network pharmacology. Finally, molecular docking was applied to verify the acquired key targets. The results showed that SGN exerted a certain gastroprotective effect via multiple pathways and targets. The effects of SGN were mainly caused by the key active ingredients isofraxidin, rosmarinic, and caffeic acid, which regulate hub targets, such as PTGS2, MAPK1, and KDR, which maintain the homeostasis of related metabolites. Signal pathways involved energy metabolism as well as immune and amino acid metabolism. Overall, the multi-omics techniques were proven to be promising tools in illuminating the mechanism of action of SGN in protecting against diseases. This integrated strategy provides a basis for further research and clinical application of SGN.
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Affiliation(s)
- Chao Li
- School of Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rou Wen
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China
| | - DeWen Liu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - LiPing Yan
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Qianfeng Gong
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China
- *Correspondence: Qianfeng Gong, ; Huan Yu,
| | - Huan Yu
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China
- *Correspondence: Qianfeng Gong, ; Huan Yu,
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Ji XK, Madhurapantula SV, He G, Wang KY, Song CH, Zhang JY, Wang KJ. Genetic variant of cyclooxygenase-2 in gastric cancer: More inflammation and susceptibility. World J Gastroenterol 2021; 27:4653-4666. [PMID: 34366627 PMCID: PMC8326261 DOI: 10.3748/wjg.v27.i28.4653] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/17/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer accounts for the majority cancer-related deaths worldwide. Although various methods have considerably improved the screening, diagnosis, and treatment of gastric cancer, its incidence is still high in Asia, and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%. Therefore, more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer. Cyclooxygenase-2 (COX-2) is considered to be the key inducible enzyme in prostaglandins (PGs) synthesis, which is involved in multiple pathways in the inflammatory response. For example, inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway. In these processes, the production of an inflammatory microenvironment promotes the occurrence of gastric cancer. Epidemiological studies have also indicated that non-steroidal anti-inflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2. However, clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects, especially in the cardiovascular system. Given these side effects and low treatment efficacy, new therapeutic approaches and early screening strategies are urgently needed. Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis. However, the genetic variation analysis in these studies is incomplete and isolated, pointing out only a few single nucleotide polymorphisms (SNPs) and the risk of gastric cancer, and no comprehensive study covering the whole gene region has been carried out. In addition, copy number variation (CNV) is not mentioned. In this review, we summarize the SNPs in the whole COX-2 gene sequence, including exons, introns, and both the 5' and 3' untranslated regions. Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population. This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies, summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer, and discusses the future prospect of therapeutic intervention, which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.
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Affiliation(s)
- Xuan-Ke Ji
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sailaja Vatsalya Madhurapantula
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Gui He
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Kun-Yan Wang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Chun-Hua Song
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Jian-Ying Zhang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Kai-Juan Wang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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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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Luo MX, Long BB, Li F, Zhang C, Pan MT, Huang YQ, Chen B. Roles of Cyclooxygenase-2 gene -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer: A systematic review and meta-analysis. Gene 2018; 685:125-135. [PMID: 30391440 DOI: 10.1016/j.gene.2018.10.077] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 10/26/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND The roles of cyclooxygenase-2 (COX2) -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer were intensively analyzed, but the results of these studies were inconsistent. We conducted a meta-analysis and trial sequential analysis to elucidate the associations between these two COX2 polymorphisms and gastric cancer risk. METHODS Eligible studies were searched in PubMed, Embase, Cochrane library databases, China National Knowledge Infrastructure, Vip, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the genetic correlation between COX2 polymorphisms and gastric cancer susceptibility in five genetic models. Trial sequential analysis (TSA) was conducted to estimate whether the evidence of the results is sufficient. Furthermore, their interactions with Helicobacter pylori (H. pylori) or smoking in gastric cancer were also assessed using a case-only method. RESULTS The COX2 gene -765G > C polymorphism showed no significant association with gastric cancer susceptibility under all the five genetic models (take the allelic model for example: OR = 1.41, 95% CI: 0.95-2.09) in total analysis, and the stratification analysis by ethnicity indicated a similar association in Caucasian group under four genetic models (allelic model, dominant model, homozygous model, and heterozygous model). But in the subgroup of the Asian population, the -765G > C polymorphism was significantly associated with gastric cancer risk under the same contrast. The COX2 -1195G > A polymorphism showed significant correlation with gastric cancer susceptibility in total analysis, and stratification analysis by ethnicity also revealed a similar association in both Asian and Caucasian groups under the same contrast. Moreover, TSA confirmed such associations. Both H. pylori infection and cigarette smoking interacted with -765 C allele in gastric cancer (OR = 3.79, 95% CI: 1.15-12.43 and OR = 2.48, 95% CI: 1.38-4.48, respectively), but not in -1195 A allele (OR = 1.96, 95% CI: 0.62-6.21, and OR = 1.24, 95% CI: 0.93-1.64, respectively). CONCLUSIONS COX2 -765G > C polymorphism may serve as a genetic biomarker of gastric cancer in Asians, but not in Caucasians. COX2 -1195G > A polymorphism may serve as a genetic biomarker of gastric cancer in both Asians and Caucasians. The -765G > C, rather than -1195G > A polymorphism interacted with H. pylori infection or cigarette smoking to increase gastric cancer risk.
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Affiliation(s)
- Ming-Xu Luo
- Department of Gastrointestinal Surgery, Xiamen Humanity Hospital, Xiamen, China; Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Bin-Bin Long
- The Third Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Fei Li
- Endoscopy Center, The Third Hospital of Zhangzhou, Zhangzhou, China
| | - Chao Zhang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Meng-Ting Pan
- Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Yu-Qiang Huang
- Teaching and Research Section of Surgery, The First Clinical College of Fujian Medical University, Fuzhou, China
| | - Bo Chen
- Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China; Teaching and Research Section of Surgery, The First Clinical College of Fujian Medical University, Fuzhou, China.
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Zhao F, Cao Y, Zhu H, Huang M, Yi C, Huang Y. The -765G>C polymorphism in the cyclooxygenase-2 gene and digestive system cancer: a meta-analysis. Asian Pac J Cancer Prev 2015; 15:8301-10. [PMID: 25339021 DOI: 10.7314/apjcp.2014.15.19.8301] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. MATERIALS AND METHODS A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBM databases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. RESULTS A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. The results indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer when compared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers (GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, and p< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type (GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk for gastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophageal cancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in then population-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC) studies. CONCLUSIONS This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is a potential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.
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Affiliation(s)
- Fen Zhao
- Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Sichuan Province, China E-mail :
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Campanholo VMDLP, Felipe AV, de Lima JM, Pimenta CAM, Ventura RM, Forones NM. -765 g>c polymorphism of the cox-2 gene and gastric cancer risk in Brazilian population. ARQUIVOS DE GASTROENTEROLOGIA 2015; 51:79-83. [PMID: 25003256 DOI: 10.1590/s0004-28032014000200002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Accepted: 12/02/2013] [Indexed: 02/07/2023]
Abstract
CONTEXT Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX) are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. OBJECTIVES To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. METHODS One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. RESULTS G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033). A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90). Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. CONCLUSIONS The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.
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Affiliation(s)
| | - Aledson Vitor Felipe
- Grupo de Oncologia, Disciplina de Gastroenterologia, Universidade Federal de São Paulo, Brasil, São Paulo, SP, Brasil
| | - Jacqueline Miranda de Lima
- Grupo de Oncologia, Disciplina de Gastroenterologia, Universidade Federal de São Paulo, Brasil, São Paulo, SP, Brasil
| | | | - Rogéria Maria Ventura
- Grupo de Oncologia, Disciplina de Gastroenterologia, Universidade Federal de São Paulo, Brasil, São Paulo, SP, Brasil
| | - Nora Manoukian Forones
- Grupo de Oncologia, Disciplina de Gastroenterologia, Universidade Federal de São Paulo, Brasil, São Paulo, SP, Brasil
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Zhao F, Zhu H, Huang M, Yi C, Huang Y. The 765G>C polymorphism in the cyclooxygenase-2 gene and gastric cancer risk: an update by meta-analysis. Asian Pac J Cancer Prev 2015; 15:2863-8. [PMID: 24761915 DOI: 10.7314/apjcp.2014.15.6.2863] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigated for association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aim of this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene for GC. MATERIALS AND METHODS We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10, 2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. RESULTS A total of 1,874 cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated that the variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG (odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18, and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07, 95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysis by Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58, 95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). CONCLUSIONS This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GC in Asians and Indians.
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Affiliation(s)
- Fen Zhao
- Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China E-mail :
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Gharib AF, Karam RA, Abd El Rahman TM, Elsawy WH. COX-2 polymorphisms -765G→C and -1195A→G and hepatocellular carcinoma risk. Gene 2014; 543:234-6. [PMID: 24720952 DOI: 10.1016/j.gene.2014.04.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 04/02/2014] [Accepted: 04/04/2014] [Indexed: 12/19/2022]
Abstract
Cyclooxygenase-2 (COX-2) is overexpressed in hepatocellular carcinoma (HCC) and considered to play a role in hepatic carcinogenesis. Our aim was to examine the associations between polymorphisms in COX-2 -765G→C and -1195A→G and risk of HCC. We conducted a case-control study including 120 patients with HCC and 130 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -765G→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. No significant difference was observed in the genotype distribution of the -765G→C polymorphism between patients and controls. The -1195AA genotype was associated with an increased risk of developing HCC (OR, 2.5; 95%CI, 1.18-5.37). The A allele was present significantly more often in HCC patients (OR 1.5; 95%CI, 1.05-2.14). In conclusion, our results demonstrated that the -1195AA genotype and A allele have an important role in HCC risk in Egyptian patients.
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Affiliation(s)
- Aml F Gharib
- Department of Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Rehab A Karam
- Department of Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt; Department of Biochemistry, Faculty of Medicine, Taif University, Al Taif, Saudi Arabia.
| | - Tamer M Abd El Rahman
- Department of Surgery, Faculty of Medicine, Taif University, Al Taif, Saudi Arabia; Department of Surgery, Benha Teaching Hospital, Benha, Egypt
| | - Wael H Elsawy
- Department of Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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Ahmadi B, Nikzamir A, Ghafari SM, Mohamadzadeh G, Latifi M, Bafandeh A, Fathi M, Yekaninejad MS, Nikzamir M. Lack of association between cyclooxygenase 2-765G/C gene polymorphism and breast cancer risk in Ahvaz, west-south Iran. Mol Biol Rep 2014; 41:997-1001. [PMID: 24402873 DOI: 10.1007/s11033-013-2944-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2013] [Accepted: 12/20/2013] [Indexed: 01/22/2023]
Abstract
Cyclooxygenases are key enzymes in conversion of arachidonic acid into prostaglandin H2. Cyclooxygenase-2 (COX-2) increases prostaglandins in neoplastic tissue. COX-2 has important roles in cell proliferation cancers, angiogenesis, and alzheimer. COX-2 is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Our main objective was to evaluated the association of polymorphism COX-2 with risk of breast cancer in khouzestan province, and the second objective of the study was to evaluate the association with biochemistry parameters. This study consisting of 150 patients with breast cancer and 120 normal DNA was extracted from the white blood cells. Polymorphism cox2 gene was detected by polymerase chain reaction according to the standard methods. The profile lipids and estrogen were measured in two groups by standard methods. Chi square analysis showed that there was no association between breast cancer risk and COX-2 -765G>C genotype and alleles. Also, no association were observed between -765G>C polymorphism and biochemistry parameters. A multiple logistic regression model with cox2 genotypes and LDL and HDL as covariates revealed that there is no significant association between cox2 genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer.
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Affiliation(s)
- Behnaz Ahmadi
- Department of Biochemistry, Faculty of Medicine, Ahvaz Jondishapour University of Medical Sciences, Ahvaz, Iran
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Wang XF, Huang MZ, Zhang XW, Hua RX, Guo WJ. COX-2-765G>C polymorphism increases the risk of cancer: a meta-analysis. PLoS One 2013; 8:e73213. [PMID: 24023834 PMCID: PMC3762903 DOI: 10.1371/journal.pone.0073213] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Accepted: 07/18/2013] [Indexed: 02/07/2023] Open
Abstract
Background Chronic inflammation has been regarded as an important mechanism in carcinogenesis. Inflammation-associated genetic variants have been highly associated with cancer risk. Polymorphisms in the gene cyclooxygenase-2 (COX-2), a pro-inflammation factor, have been suggested to alter the risk of multiple tumors, but the findings of various studies are not consistent. Methods A literature search through February 2013 was performed using PubMed, EMBASE, and CNKI databases. We used odds ratios (ORs) with confidence intervals (CIs) of 95% to assess the strength of the association between the COX-2-765G>C polymorphism and cancer risk in a random-effect model. We also assessed heterogeneity and publication bias. Results In total, 65 articles with 29,487 cancer cases and 39,212 non-cancer controls were included in this meta-analysis. The pooled OR (95% CIs) in the co-dominant model (GC vs. GG) was 1.11 (1.02–1.22), and in the dominant model ((CC+GC) vs. GG), the pooled OR was 1.12 (1.02–1.23). In the subgroup analysis, stratified by cancer type and race, significant associations were found between the-765 C allele and higher risk for gastric cancer, leukemia, pancreatic cancer, and cancer in the Asian population. Conclusion In summary, the COX-2-765 C allele was related to increased cancer susceptibility, especially gastric cancer and cancer in the Asian population.
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Affiliation(s)
- Xiao-feng Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ming-zhu Huang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiao-wei Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Rui-xi Hua
- Department of Medical Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wei-jian Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- * E-mail:
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Yan WF, Sun PC, Nie CF, Wu G. Cyclooxygenase-2 polymorphisms were associated with the risk of gastric cancer: evidence from a meta-analysis based on case-control studies. Tumour Biol 2013; 34:3323-30. [PMID: 23775011 DOI: 10.1007/s13277-013-0901-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 05/27/2013] [Indexed: 12/12/2022] Open
Abstract
The associations between cyclooxygenase-2 (COX-2) polymorphisms (-765G>C, -1195G>A, and -587G>A) and risk of gastric cancer have been investigated, but the results were inconsistent. The aim of this study was to explore the associations between COX-2 polymorphisms and risk of gastric cancer using a meta-analytic method. We searched the databases of PubMed, Embase, and Wanfang (Chinese database) to identify the eligible studies. Odds ratio and 95 % confidence interval (OR and 95% CI) were used as effect size, and combined analyses were conducted using fixed- or random-effects model. Overall, ten studies for COX-2-765G>C, six studies for -1195G>A, and three studies for -587G>A were included in this study. The results for combined analysis for COX-2-765G>C indicated that C allele was significantly associated with increased risk of gastric cancer compared with G allele, especially for Asians (OR and 95 % CI: 1.58 (1.06-2.35), P(z-test) = 0.03, and P heterogeneity <0.01 for CC+GC vs. GG). In addition, the A allele of COX-2-1195G>A was also significantly associated with risk of gastric cancer compared with G allele (OR and 95 % CI: 1.20 (1.09-1.32), P(z-test) <0.001, and P(heterogeneity) = 0.82 for A carriers vs. G carriers). In contrast, the COX-2-587G>A polymorphism was not associated with risks of gastric cancer. In summary, this meta-analysis indicated that the COX-2-765G>C and -1195G>A polymorphisms were significantly associated with risk of gastric cancer development.
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Affiliation(s)
- Wen Feng Yan
- Department of General Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, People's Republic of China
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Saxena A, Shukla SK, Prasad KN, Ghoshal UC. Analysis of p53, K-ras gene mutation & Helicobacter pylori infection in patients with gastric cancer & peptic ulcer disease at a tertiary care hospital in north India. Indian J Med Res 2012; 136:664-70. [PMID: 23168708 PMCID: PMC3516035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND & OBJECTIVES Mutations in the oncogene and tumour suppressor genes play an important role in carcinogenesis. We investigated the association of p53 and K-ras gene mutation and Helicobacter pylori infection in patients with gastric cancer (GC) and peptic ulcer disease (PUD) attending a tertiary care hospital in north India. METHODS In total, 348 adult patients [62 GC, 45 PUD and 241 non-ulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. Mutation in the exon 5-8 of p53 gene was analyzed by PCR-single stranded conformational polymorphism (SSCP) and confirmed by sequence analysis. K-ras gene codon 12 mutation was analyzed by PCR-based restriction fragment length polymorphism. RESULTS Overall p53 gene mutation was found in 4.6 per cent of the study population, and its distribution in GC, PUD and NUD was 21, 4.4 and 0.4 per cent, respectively. p53 gene mutation was significantly higher in patients with GC than PUD (P<0.05) and NUD (P<0.001). No difference in p53 gene mutation was observed between H. pylori infected and non-infected individuals. K-ras gene mutation was absent in all the patients. INTERPRETATION & CONCLUSIONS Our results show that p53 gene mutation may be associated with gastric carcinogenesis independent to H. pylori infection and absence of K-ras gene mutation questions its role in the pathogenesis of GC and PUD in Indian patients.
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Affiliation(s)
- Ashish Saxena
- Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Texas, USA
| | - Sanket Kumar Shukla
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Kashi Nath Prasad
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India,Reprint requests: Dr Kashi N. Prasad, Professor, Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India e-mail:
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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García-González MA, Nicolás-Pérez D, Lanas A, Bujanda L, Carrera P, Benito R, Strunk M, Sopeña F, Santolaria S, Piazuelo E, Jiménez P, Campo R, Espinel J, Manzano M, Geijo F, Pellisé M, González-Huix F, Espinós J, Zaballa M, Titó L, Barranco L, Pazo R, Quintero E. Prognostic role of host cyclooxygenase and cytokine genotypes in a Caucasian cohort of patients with gastric adenocarcinoma. PLoS One 2012; 7:e46179. [PMID: 23029430 PMCID: PMC3460851 DOI: 10.1371/journal.pone.0046179] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Accepted: 08/30/2012] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Genetic factors influencing the prognosis of gastric adenocarcinoma (GAC) are not well known. Given the relevance of cytokines and other pro-inflammatory mediators in cancer progression and invasiveness, we aimed to assess the prognostic role of several functional cytokine and cyclooxygenase gene polymorphisms in patients with GAC. METHODOLOGY Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (IL1B, TNFA, LTA, IL6, IL12p40), anti-inflammatory (IL4, IL1RN, IL10, TGFB1) cytokine, and cyclooxygenase (PTGS1 and PTGS2) genes by PCR, RFLP and TaqMan assays. Clinical and histological information was collected prospectively. Survival curves were estimated by the Kaplan-Meier method and compared using the log rank test. Outcome was determined by analysis of Cox proportional hazards, adjusting for confounding factors. RESULTS The median follow-up period and median overall survival (OS) time were 9.9 months (range 0.4-120.3) and 10.9 months (95% CI: 8.9-14.1), respectively. Multivariate analysis identified tumor stages III (HR, 3.23; 95% CI:2-5.22) and IV (HR, 5.5; 95% CI: 3.51-8.63) as independent factors associated with a significantly reduced OS, whereas surgical treatment (HR: 0.44; 95%CI: 0.3-0.6) was related to a better prognosis of the disease. Concerning genetic factors, none of the 23 polymorphisms evaluated in the current study did influence survival. Moreover, no gene-environment interactions on GAC prognosis were observed. CONCLUSIONS Our results show that, in our population, the panel of selected pro- and anti-inflammatory cytokine, and cyclooxygenase gene polymorphisms are not relevant in determining the prognosis of gastric adenocarcinoma.
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Shukla SK, Prasad KN, Tripathi A, Singh A, Saxena A, Ghoshal UC, Krishnani N, Husain N. Epstein-Barr virus DNA load and its association with Helicobacter pylori infection in gastroduodenal diseases. Braz J Infect Dis 2012. [PMID: 22218519 DOI: 10.1016/s1413-8670(11)70255-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
UNLABELLED Helicobacter pylori and Epstein-Barr virus (EBV) infections are common worldwide. Although H. pylori infection is a major factor in gastroduodenal diseases, its role in association with EBV infection is unknown. OBJECTIVE To study the association of H. pylori infection and EBV DNA load in patients with gastroduodenal diseases. METHODS Biopsy samples were collected from 200 adult patients [non-ulcer dyspepsia (NUD) 100, peptic ulcer disease (PUD) 50, gastric carcinoma (GC) 50] undergoing upper gastrointestinal endoscopy. H. pylori infection was diagnosed by rapid urease test, culture, histopathology, PCR and Q-PCR. EBV DNA was detected by non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene based Q-PCR. RESULTS In patients with GC and PUD, EBV DNA was detected more often than NUD (GC versus NUD = 90% versus 37%, p < 0.001; PUD versus NUD = 70% versus 37%, p < 0.001). The dual prevalence of H. pylori infection and EBV DNA was significantly higher in patients with GC and PUD than in those with NUD. Median copy number of EBV DNA was considerably higher in GC and PUD than NUD (p < 0.01). The copy number of EBV DNA was significantly higher in H. pylori infected patients (p = 0.015). The number of ureA gene copies was also found to be significantly higher in PUD and NUD with presence of EBV DNA. However, in GC no significant difference was seen between EBV positive and negative status. CONCLUSION There was a trend for higher EBV DNA load in H. pylori positive individuals suggesting a probable role of H. pylori in modulating the conversion of EBV to its lytic phase.
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Affiliation(s)
- Sanket Kumar Shukla
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Shin WG, Kim HJ, Cho SJ, Kim HS, Kim KH, Jang MK, Lee JH, Kim HY. The COX-2-1195AA Genotype Is Associated with Diffuse-Type Gastric Cancer in Korea. Gut Liver 2012; 6:321-7. [PMID: 22844559 PMCID: PMC3404168 DOI: 10.5009/gnl.2012.6.3.321] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Accepted: 11/28/2011] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND/AIMS The potential role of the cyclooxygenase (COX)-2 polymorphism has been reported in relation to the risk of gastrointestinal tract malignancies. Therefore, we investigated whether COX-2 polymorphisms are associated with the risk of gastric cancer (GC) in Korea, one of the areas with a high prevalence of this condition. METHODS We evaluated the genotypic frequencies of COX-2-765 and -1195 in 100 peptic ulcer patients, 100 GC patients, and 100 healthy controls. The polymorphisms of the COX-2-765 and -1195 genes were analyzed by polymerase chain reaction and restriction fragment length polymorphisms. RESULTS The frequencies of the COX-2-1195 GG, GA, and AA genotype were 20%, 60%, and 20% in intestinal-type GC and 8%, 48%, and 44% in diffuse-type GC, respectively (p=0.021). There were no significant differences in the frequency of COX-2-765 genotypes between intestinal-type GC and diffuse-type GC (p=0.603). Age- and sex-adjusted logistic regression analysis showed that the COX-2-1195 AA genotype was the independent risk factor of diffuse-type GC compared with the COX-2-1195 GG genotype (p=0.041; odds ratio, 6.22; 95% confidence interval, 1.077 to 35.870). CONCLUSIONS The COX-2-1195 AA genotype may render subjects more susceptible to diffuse-type GC.
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Affiliation(s)
- Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea
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LI YUCHUN, DAI LIPING, ZHANG JIANZHONG, WANG PENG, CHAI YURONG, YE HUA, ZHANG JIANYING, WANG KAIJUAN. Cyclooxygenase-2 polymorphisms and the risk of gastric cancer in various degrees of relationship in the Chinese Han population. Oncol Lett 2012; 3:107-112. [PMID: 22740864 PMCID: PMC3464087 DOI: 10.3892/ol.2011.426] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Accepted: 09/08/2011] [Indexed: 12/21/2022] Open
Abstract
A number of studies have shown that cyclooxygenase-2 (COX-2) gene polymorphisms were associated with gastric cancer. However, the results from different research groups have not been consistent. The present study aimed to investigate the association between polymorphisms of the cyclooxygenase-2 promoter region (-1195G>A, -765G>C) and gastric cancer patients with various degrees of relationship in the Chinese Han population. COX-2-1195G>A and COX-2-765G>C polymorphisms in 296 gastric cancer patients and 319 control family members were genotyped using polymerase chain reaction-restriction fragment length polymorphism. An increased risk of gastric cancer was observed in subjects with the COX-2-1195AA genotype (OR=2.03; 95% CI, 1.27-3.22), and the association strength decreased as the degree of relationship decreased. Stratification analysis revealed that the OR value of COX-2-1195AA genotype and A carriers exhibited synergy with Helicobacter pylori (H. pylori) infection (AA genotype: OR=2.96; 95% CI, 1.57-5.58; A carriers: OR=2.04; 95% CI, 1.18-3.52). No significant difference was found in each genotype of COX-2-765G>C between gastric cancer patients and control family members, as well as gastric cancer patients with various degrees of relationship. Our study demonstrated that the polymorphism of COX-2-1195AA genotype may be a risk factor for gastric cancer patients with various degrees of relationship among the Chinese Han population. H. pylori infection therefore may enhance the risk of gastric cancer in individuals with the COX-2-1195 AA genotype.
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Affiliation(s)
- YUCHUN LI
- Department of Epidemiology, College of Public Health, Zhengzhou 450001
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052
| | - LIPING DAI
- Department of Epidemiology, College of Public Health, Zhengzhou 450001
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052
| | - JIANZHONG ZHANG
- Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China
| | - PENG WANG
- Department of Epidemiology, College of Public Health, Zhengzhou 450001
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052
| | - YURONG CHAI
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052
| | - HUA YE
- Department of Epidemiology, College of Public Health, Zhengzhou 450001
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052
| | - JIANYING ZHANG
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052
- Department of Biological Sciences, University of Texas 79968, El Paso, TX, USA
| | - KAIJUAN WANG
- Department of Epidemiology, College of Public Health, Zhengzhou 450001
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052
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Influence of age and gender on association between -765G > C COX-2 genetic polymorphism and gastric adenocarcinoma risk: a case-control study in Iran. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2012; 5:29-34. [PMID: 24834195 PMCID: PMC4017443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Accepted: 11/18/2011] [Indexed: 12/02/2022]
Abstract
AIM The purpose of this study was to investigate the possible influence of age and gender on association between -765G > C COX-2 genetic polymorphism and gastric adenocarcinoma risk in Iranian patients. BACKGROUND The promoter polymorphism of COX-2 gene -765G > C has been described to play an important role in many cancers such as gastric cancer. PATIENTS AND METHODS We carried out single-nucleotide polymorphism analysis in Iranian samples including 91 patients and 91 control normal using PCR- RFLP technique. RESULTS Statistical analysis revealed no significant association between GG, GC and CC genotypes and risk of gastric adenocarcinoma. However differences were considered significant (P=0.043) for female subjects with C carrier genotypes (GC and CC) and gastric adenocarcinoma when compared with male patients (P=0.645) and control groups (P=0.653). Also, there was a statistically significant difference between increasing of age and susceptibility for gastric adenocarcinoma (Odd Ratio=1.125, 95% CI=1.089-1.162). CONCLUSION These results suggested that Iranian C carrier females can be more susceptible for gastric adenocarcinoma in comparison with control group. Also increasing of age should be considered as a risk factor for this disease.
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He J, Zhang Q, Ren Z, Li Y, Li X, Zhou W, Zhang H, Meng W, Yan J, He W. Cyclooxygenase-2 -765 G/C polymorphisms and susceptibility to hepatitis B-related liver cancer in Han Chinese population. Mol Biol Rep 2011; 39:4163-8. [PMID: 21800055 DOI: 10.1007/s11033-011-1199-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Accepted: 07/11/2011] [Indexed: 12/17/2022]
Abstract
To investigate the relationship of cyclooxygenase-2 (COX-2) polymorphisms [COX-2 -765 G/C (rs 20417)] and susceptibility to hepatitis B-related liver cancer in Han Chinese population. The polymorphisms of COX-2 -765 G/C was detected by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in 300 patients with hepatitis B, 300 patients with cirrhosis, 300 patients with primary liver carcinoma and 300 health controls. The COX-2 -765 G/C genotypes were GG, GC and CC. There frequencies in the hepatitis B patients were 80.33, 17.67 and 2.00%; in the cirrhosis patients were 77.67, 18.00 and 4.33%; in the patients with primary liver carcinoma were 65.67, 28.33 and 6.00% and in the heathy controls were 87.00, 12.33 and 0.67%, respectively, COX-2 -765 C allele carriers had an increased risk of hepatitis B-related liver cancer. COX-2 -765 C allele carriers having drinking history or family history of liver cancer had higher risk for HCC. COX-2 -765 C allele genotype, drinking history and family history of liver cancer may increase the susceptibility to hepatitis B-related liver cancer in Gansu province, China.
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Affiliation(s)
- Jianhong He
- The Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China
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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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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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Liu JL, Liang Y, Wang ZN, Zhou X, Xing LL. Cyclooxygenase-2 polymorphisms and susceptibility to gastric carcinoma: A meta-analysis. World J Gastroenterol 2010; 16:5510-7. [PMID: 21086572 PMCID: PMC2988247 DOI: 10.3748/wjg.v16.i43.5510] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association of the cyclooxygenases-2 (COX-2) polymorphisms and susceptibility to gastric cancer (GC) by means of meta-analysis.
METHODS: Publications addressing the association between polymorphisms of COX-2 and susceptibility to GC were selected from the MEDLINE, EMBASE and CBMdisc databases. Data was extracted from the studies by 2 independent reviewers. The meta-analyses were performed by RevMan 5.0.23. From these data, odds ratio (OR) with 95% confidence interval (CI) was calculated.
RESULTS: Ten studies were retrieved reporting a total of 11 COX-2 polymorphisms. Carriers of -765C, -1195A, -1290G, *2430T alleles and *429TT genotype revealed increased risk for GC (OR = 1.71, 95% CI: 1.01-2.90, P = 0.05; OR = 1.58, 95% CI: 1.05-2.38, P = 0.03; OR = 1.55, 95% CI: 1.01-2.39, P = 0.05; OR = 2.62, 95% CI: 1.20-5.73, P = 0.02 and OR = 0.74, 95% CI: 0.59-0.95, P = 0.02, respectively).
CONCLUSION: The -765C, -1195A, -1290G, *2430T alleles and *429TT genotype of COX-2 polymorphisms were determined a significant association with susceptibility to GC.
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Dong J, Dai J, Zhang M, Hu Z, Shen H. Potentially functional COX-2-1195G>A polymorphism increases the risk of digestive system cancers: a meta-analysis. J Gastroenterol Hepatol 2010; 25:1042-50. [PMID: 20594217 DOI: 10.1111/j.1440-1746.2010.06293.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Three potentially functional polymorphisms: -765G>C, -1195G>A, and 8473T>C in the cyclooxygenase-2 (COX-2) gene were identified and proposed to be associated with cancer susceptibility. The aim of this meta-analysis was to evaluate the association between these three polymorphisms and the risk of cancer in diverse populations. METHODS All case-control studies published up to November 2009 on the association between the three polymorphisms of COX-2 and cancer risk were identified by searching PubMed. The cancer risk associated with the three polymorphisms of the COX-2 gene was estimated for each study by OR together with its 95% confidence interval (CI), respectively. RESULTS A total of 47 case-control studies were included, and variant genotypes GA/AA of -1195G>A were associated with a significantly increased cancer risk (GA/AA vs GG: odds ratio [OR], 1.29; 95% CI, 1.18-1.41; P(heterogeneity) = 0.113), and this significant association was mainly observed within cancers of the digestive system (e.g. colorectal, gastric, esophageal, oral, biliary tract, gallbladder, and pancreatic) without between-study heterogeneity (GA/AA vs GG: OR, 1.36; 95% CI; 1.23-1.51; P(heterogeneity) = 0.149). Furthermore, a stratification analysis showed that the risk of COX-2-1195G>A associated with cancers in the digestive system was more evident among Asians than Caucasians. However, for COX-2-765G>C and 8473T>C, no convincing association between the two polymorphisms and risk of cancer or cancer type was observed. CONCLUSIONS The effect of three potentially functional polymorphisms (-765G>C, -1195G>A, and 8473T>C) in the COX-2 gene on cancer risk provided evidence that the COX-2-1195G>A polymorphism was significantly associated with increased risk of digestive system cancers, especially among Asian populations.
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Affiliation(s)
- Jing Dong
- Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China
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Aubin F, Courivaud C, Bamoulid J, Loupy A, Deschamps M, Ferrand C, Le Corre D, Tiberghien P, Chalopin JM, Legendre C, Thervet E, Humbert P, Saas P, Ducloux D. Influence of cyclooxygenase-2 (COX-2) gene promoter polymorphism at position -765 on skin cancer after renal transplantation. J Invest Dermatol 2010; 130:2134-6. [PMID: 20445548 DOI: 10.1038/jid.2010.116] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Hoff JH, Morsche RHMT, Roelofs HMJ, Logt EMJVD, Nagengast FM, Peters WHM. COX-2 polymorphisms -765G→C and -1195A→G and colorectal cancer risk. World J Gastroenterol 2009; 15:4561-5. [PMID: 19777615 PMCID: PMC2752001 DOI: 10.3748/wjg.15.4561] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer (CRC) in a Dutch population.
METHODS: This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -765G→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression.
RESULTS: The -765GG genotype was associated with an increased risk of developing CRC (OR, 1.45; 95% CI, 1.03-2.04). No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls (OR 0.44; 95% CI, 0.22-0.85). When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls (OR(AG/AC) 0.78; 95% CI, 0.57-1.06).
CONCLUSION: The -765GG genotype is associated with an increased risk of developing CRC and the GG/AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.
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Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B. Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squmaous cell carcinoma. Mutat Res 2009; 663:52-59. [PMID: 19428370 DOI: 10.1016/j.mrfmmm.2009.01.007] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2008] [Revised: 01/09/2009] [Accepted: 01/26/2009] [Indexed: 01/11/2023]
Abstract
Cyclooxygenase-2 (COX-2) influences carcinogenesis through regulation of angiogenesis, apoptosis and cytokine expression. We aimed to evaluate association of COX-2 polymorphisms with predisposition to esophageal squamous cell carcinoma (ESCC), its phenotype variability and modulation of environmental risk in northern Indian population. We genotyped 174 patients with ESCC and 216 controls for COX-2 gene polymorphisms (-765G>C; -1195G>A; -1290A>G; 3'UTR 8473T>C) using PCR-RFLP. Data were statistically analyzed using chi-square test and logistic regression model. COX-2 -765C allele carriers were at increased risk for ESCC (OR=1.66; 95% CI=1.08-2.54; P=0.004). However, -1195G>A; -1290A>G; 3'UTR 8473T>C polymorphisms of COX-2 gene were not significantly associated with ESCC. We observed significantly enhanced risk for ESCC due to interaction between COX-2 -1195GAx-765GC+CC genotypes (OR=4.60; 95% CI=1.63-13.01; P=0.004). High risk to ESCC was also observed with respect to COX-2 haplotypes, A(-1290)G(-1195)C(-765)T(8473) and A(-1290)A(-1195)C(-765)T(8473) [OR=3.35; 95% CI=0.83-13.44; P=0.089; OR=4.28; 95% CI=0.43-42.40; P=0.246] however, it was not statistically significant. Stratification of subjects based on gender showed that females were at higher risk for ESCC due to COX-2 -765C carrier genotypes (OR=2.97; 95% CI=1.23-7.18; P=0.016). In association of genotypes with clinical characteristics, -765C carrier genotype conferred risk of ESCC in middle third of esophagus (OR=1.78; 95% CI=1.08-2.93; P=0.023). In case-only analysis, interaction of environmental risk factors and COX-2 genotypes did not further modulate the risk for ESCC. In summary, COX-2 -765G>C polymorphism confers ESCC susceptibility particularly in females and patients with middle third anatomical location of the tumor. Interaction of COX-2 -1195GA and -765C carrier genotypes also modulates ESCC risk.
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Affiliation(s)
- Rohit Upadhyay
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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Cyclooxygenase polymorphisms in gastric and colorectal carcinogenesis: are conclusive results available? Eur J Gastroenterol Hepatol 2009; 21:76-91. [PMID: 19060633 DOI: 10.1097/meg.0b013e32830ce7ba] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Cyclooxygenases (COX) are important enzymes not only in the maintenance of mucosal integrity but also in pathological processes, namely in inflammation and tumor development in the gastrointestinal tract. Our goal was to understand whether there is a clear role for COX polymorphisms in gastric and colorectal carcinogenesis. METHODS A systematic review was conducted on observational studies assessing the involvement of COX polymorphisms at the onset of gastric or colorectal lesions, retrieved through a MEDLINE database search by May 2008. The dominant genetic model was assumed for each polymorphism and a random-effect model was used for pooling results. RESULTS Twenty-two studies were retrieved reporting a total of 26 COX polymorphisms (nine in COX1 and 17 in COX2 genes). Carriers of -1329A, -899C alleles, and *429TT genotype revealed increased risk for gastric cancer [odds ratio (OR)=1.83; 95% confidence interval (CI): 1.07-3.10, OR=2.02; 95% CI: 1.00-4.10 and OR=1.34; 95% CI: 1.06-1.71, respectively). For colorectal lesions, the -899G>C and -1329G>A polymorphisms also showed an increased risk for cancer (OR=1.35; 95% CI: 1.01-1.81 and OR=1.36; 95% CI: 1.11-1.66, respectively). Furthermore, C allele carriers of V102V single nucleotide polymorphisms presented a decreased risk for colorectal adenoma onset (OR=0.77; 95% CI: 0.58-1.03). CONCLUSION Although further studies, namely cohorts and/or adequately matched case-control studies, are required to unravel the impact of most COX polymorphisms, clearly there are evidences that support the involvement of -899G>C and -1329G>A COX2 polymorphisms in either gastric or colorectal carcinogenesis. These markers could be used to optimize management strategies (follow-up and/or chemoprevention).
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