Cyclooxygenase-2 Polymorphisms Research Articles

COX-2 rs5275 and rs689466 polymorphism and risk of lung cancer: A PRISMA-compliant meta-analysis.

Background:Cyclooxygenase-2 (COX-2) is an inducible enzyme that mediates the synthesis of prostaglandin, which plays an important role in the inflammation response. The overexpression of COX-2 in lung cancer has been found in several studies, suggesting that COX-2 contributes to carcinogenesis. There are many previous case-control studies focused on the association between COX-2 polymorphism and lung cancer risk, however, the conclusion remained controversial.Objectives:We performed this meta-analysis to evaluate the association between COX-2 rs5275 and rs689466 polymorphism and susceptibility to lung cancer.Methods:A systematic literature research was conducted on PubMed, Embase, Cochrane Library, OVID, Web of Science, and Google Scholar up to November 30, 2017. The quality of studies was assessed by Newcastle–Ottawa scale. We combined odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models for evaluation under a fixed-effect model or random-effect model. Subgroup analysis was performed according to source of control, ethnicity, pathological types, and smoking status. Sensitivity analysis and publication bias were also conducted.Results:Eventually, 14 eligible studies were included in our meta-analysis. We found rs5275 gene polymorphism decreased the risk of lung cancer under heterozygote model (OR: 0.91, 95% CI: 0.84–0.98, P = .02). COX-2 rs689466 gene polymorphism was also related to a significantly reduced risk under allele (OR: 0.88, 95% CI: 0.82–0.95, P = .001), homozygote (OR: 0.81, 95% CI: 0.68–0.95, P = .01), heterozygote (OR: 0.81, 95% CI: 0.72–0.91, P < .001), and dominant model (OR: 0.81, 95% CI: 0.72–0.91, P < .001), except for recessive model. Subgroup analysis suggested a similar association in Asians, but not in Caucasians. Polymorphism of rs5275 was strongly associated with a reduced risk of lung adenocarcinoma according to stratified analysis by pathological types. Egger test identified no significant publication bias.Conclusions:Our meta-analysis demonstrated that COX-2 rs5275 and rs689466 polymorphism significantly decrease the risk of lung cancer in Asians but not in Caucasians, indicating COX-2 could serve as a potential diagnostic marker for lung cancer.

Selective COX2 inhibitors, other NSAIDS, and influence of COX2 polymorphisms on breast cancer risk: Results from the CECILE study

Background In the context of a possible role of chronic inflammation in cancer risk, our objective was to investigate breast cancer risk in relation to the use of selective COX2 inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, and to explore interactions of NSAIDs with COX2 genetic polymorphisms. Methods We conducted a population-based case-control study in France on breast cancer risk factors. Data on NSAID use were obtained in 871 cases and 915 controls using a standardized questionnaire, and 7 single nucleotide polymorphisms in the COX2 gene were genotyped in 811 cases and 829 controls. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results We found an inverse association between breast cancer and NSAID use (OR = 0.80, 95% CI: 0.66–0.97), which was stronger for COX2 selective inhibitors (OR = 0.55, 95% CI: 0.35–0.86). Associations were more pronounced in salicylate non-users and overweight women. The SNP rs5275 in COX2 genes was associated with breast cancer (P = 0.01) and a significant interaction between rs5275 and NSAID use was observed (P for interaction 0.02). Conclusion Our results confirm an inverse association between NSAID use and breast cancer and highlight the role of selective COX2 inhibitors. Polymorphisms of the COX2 gene may modify the risk of breast cancer associated with NSAID use.

The Association of PNPLA3, COX-2 and DHCR7 Polymorphisms with Advanced Liver Fibrosis in Patients with HCV Mono- Infection and HCV/HIV Co-Infection

There is increasing evidence that host genetic variations may influence the natural history of chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) of PNPLA3 (rs738409), COX-2 (rs689465) and DHCR7 (rs12785878) and advanced liver fibrosis in Thai patients. A total of 220 patients with HCV mono-infection, 200 patients with HCV/HIV co-infection and 200 healthy controls were enrolled. The SNPs were detected by allelic discrimination using real-time PCR with TaqMan probes. Liver stiffness measurement (LSM) was assessed by transient elastography. Our results showed that the distribution of the studied SNPs were not significantly different between the HCV mono- and co-infected groups. The frequencies AG and GG genotypes of rs689465 and GG genotype of rs12785878 were less commonly found in the HCV mono- and co-infected groups compare with healthy controls (P<0.01). Among patients with HCV infection, older age, HIV co-infection, GG genotype of rs738409 and GG genotype of rs689465 were independently associated with advanced liver fibrosis (LSM≥9.5 kPa) in multivariate analysis. Moreover, the percentage of patients with advanced liver fibrosis increased significantly along with the accumulated numbers of these risk genotypes. In conclusion, PNPLA3 (rs738409) and COX-2 (rs689465) polymorphisms were associated with advanced liver fibrosis in patients with HCV mono- and co-infection, suggesting that these variants might play an important role in progressive liver fibrosis in these patients.

COX2 and NOS3 gene polymorphisms in women with gestational diabetes.

Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnancy. Low-grade inflammation plays an important role in the pathogenesis of this disorder. The present study aimed to examine the association between COX2 (rs6681231) and NOS3 (rs1799983 and rs2070744) gene polymorphisms and GDM. The study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28weeks of gestation. We observed an increased frequency of COX2 rs6681231 CC and GC genotype carriers among women with GDM (CC+GC versus GG, odds ratio=1.55, 95% confidence interval=1.01-2.36, p=0.043; C versus G, odds ratio=1.59, 95% confidence interval=1.10-2.30, p=0.013). There were no statistically significant differences in the distribution of NOS3 rs1799983 and rs2070744 between GDM and healthy women. Moreover, among women treated with insulin, we observed an increased frequency of COX2 rs6681231 CC and NOS3 rs1799983 TT genotype carriers. The results of the present study suggest that the CC genotype of the COX2 rs6681231 polymorphism is associated with an increased risk of GDM and the need for insulin therapy, whereas the TT genotype of the NOS3 rs1799983 polymorphism may be associated with the need for insulin therapy in women with GDM.

Cyclooxygenase-2 (COX-2) polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population

Background: Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2 gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases. However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and susceptibility to post-traumatic osteomyelitis in Chinese population.Methods: A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were genotyped for rs20417 and rs689466 using the SNaPshot genotyping method. Chi-square test was used to compare differences of genotype distributions as well as outcomes of five different genetic models between the two groups.Results: Significant association was found between rs689466 and post-traumatic osteomyelitis by recessive model (GG vs. AA + AG) (OR = 1.74, 95% CI: 1.098–2.755, p = .018). Although no statistical differences were identified of rs689466 between the two groups by allele model (p = .098) or homozygous model (p = .084), outcomes revealed a tendency that allele G may be a risk factor and people of GG genotype may be in a higher risk to develop post-traumatic osteomyelitis in Chinese population. However, no significant link was found between rs20417 and susceptibility to post-traumatic osteomyelitis in this Chinese cohort.Conclusions: To our knowledge, we reported for the first time that COX-2 gene polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population.

Polymorphisms in chronic rhinosinusitis with nasal polyps – a systematic review

IntroductionChronic rhinosinusitis with nasal polyps is a multifactorial disease with a complex pathophysiology involving multiple genetic and environmental factors. ObjectiveThe purpose of this work review is to focus on the importance of genetic studies in chronic rhinosinusitis with nasal polyps besides the several barriers that exists for its understanding. MethodsA systematic review on studies of association between single nucleotide polymorphisms and chronic rhinosinusitis with nasal polyps based on a PubMed/Medline and Periódicos CAPES search of all articles published between January 2005 and January 2015 was made. The search was guided on studies containing the terms polymorphisms, rhinosinusitis, and polyps. ResultsTwo studies found an association of MMP-9 and MMP-2 polymorphisms and chronic rhinosinusitis with nasal polyps, but not in patients with recurrent nasal polyps. Other studies found an association of nasal polyps with MMP-9 polymorphisms, but not with MMP-2 ones. There is evidence of an association of LTC4S, NOS2A, PTGDR, MET, COX-2, OSF-2, and LF polymorphisms and the risk of developing nasal polyps, especially when combined with chronic allergic rhinitis and asthma. ConclusionGenetic studies on chronic rhinosinusitis with nasal polyps are promising and may offer insights into its pathophysiology, which is likely affected by multiple genetic factors.

Functional analysis of polymorphisms in the COX-2 gene and risk of lung cancer.

The enzyme cyclooxygenase 2 (COX-2) is known to be involved in tumorigenesis and metastasis in certain types of cancer. Nevertheless, the prognostic value of COX-2 overexpression and its polymorphisms in patients with non-small cell lung cancer (NSCLC) have yet to be fully elucidated. The aim of the present study was to investigate the association between the three most commonly studied COX-2 gene polymorphisms (−1195 G/A, −765 G/C and 8473 T/C) with COX-2 expression and lung cancer risk in a Brazilian cohort. In the present hospital based, case-control retrospective study, 104 patients with NSCLC and 202 cancer free control subjects were genotyped for −1195 G/A, −765 G/C and 8473 T/C polymorphisms using allelic discrimination with a reverse transcription quantitative polymerase chain reaction method. COX-2 mRNA expression was analyzed in surgically resected tumors from 34 patients with NSCLC. The results revealed that COX-2 expression levels were higher in tumor tissue compared with normal lung tissue. However, this overexpression of COX-2 was not associated with the patient outcome, and furthermore, none of the analyzed polymorphisms were associated with the risk of developing lung cancer, COX-2 overexpression, or the overall survival of the patients with NSCLC. Taken together, the findings described in the present study do not support a major role for COX-2 polymorphisms and COX-2 overexpression in lung carcinogenesis within the Brazilian population.

Genetic Factors and the Risk of Periodontitis Development: Findings from a Systematic Review Composed of 13 Studies of Meta-Analysis with 71,531 Participants.

Purpose. This work aimed to synthesize the results of recent meta-analysis focusing on polymorphism in inflammatory mediators and its relation with the risk of periodontitis development. Materials and Methods. A systematic search was conducted using databases for publications prior to October 2016. Three examiners extracted data from articles with a clear association between polymorphisms in the inflammatory mediator gene and the development of periodontitis through meta-analysis using the fixed or randomized statistical models to calculate the Odds Ratio with values of P < 0.05 considered significant. Results. A total of 13 meta-analysis articles with 25 polymorphisms in seven interleukins (IL-1A, IL-1B, IL-4, IL-6, IL-8, IL-10, and IL-18), three cellular receptors (Fcγ receptors: FCGR2A, FCGR3A, and FCGR3B), and five inflammatory mediators (COX-2, MMP-2, MMP-3, MMP-8, and MMP-9), with a total of 71,531 participants, approaching different classifications of the disease. Conclusion. The study demonstrated that polymorphisms in the IL-1A, IL-1B, IL-6, IL-10, MMP-3 (chronic form), and MMP-9 (chronic form) polymorphisms were significantly associated with the risk of developing periodontitis, whereas other polymorphisms in the IL-4, IL-8, IL-18, Fcγ, COX-2, MMP-2, MMP-3 (aggressive), MMP-8, and MMP-9 (aggressive) polymorphisms had no significant association with risk of developing periodontitis.

Influence of Genetic Polymorphisms in Prostaglandin E2 Pathway (COX-2/HPGD/SLCO2A1/ABCC4) on the Risk for Colorectal Adenoma Development and Recurrence after Polypectomy

Objectives:Deregulation of prostaglandin E2 (PGE2) levels reported in colorectal carcinogenesis contributes to key steps of cancer development. Our aim was to evaluate the influence of the genetic variability in COX-2/HPGD/SLCO2A1/ABCC4 PGE2 pathway genes on the development and recurrence of colorectal adenomas.Methods:A case-control study was conducted gathering 480 unscreened individuals and 195 patients with personal history of adenomas. A total of 43 tagSNPs were characterized using the Sequenom platform or real-time PCR.Results:Ten tagSNPs were identified as susceptibility biomarkers for the development of adenomas. The top three most meaningful tagSNPs include the rs689466 in COX-2 (odds ratio (OR)=3.23; 95% confidence interval (CI): 1.52–6.86), rs6439448 in SLCO2A1 (OR=0.38; 95% CI: 0.22–0.65) and rs1751051 in ABCC4 genes (OR=2.75; 95% CI: 1.58–4.80). The best four-locus gene–gene interaction model included the rs1346271, rs1863642 and rs12500316 single nucleotide polymorphisms in HPGD and rs1678405 in ABCC4 genes and was associated with a 13-fold increased susceptibility (95% CI: 3.84–46.3, P<0.0001, cross-validation (CV) accuracy: 0.78 and CV consistency: 8/10). Interesting, in low-risk patients the ABCC4 rs9524821AA genotype was associated not only with a higher hazard ratio (HR=2.93; 95% CI: 1.07–8.03), but half of these patients had adenoma recurrence at 60 months, considerably higher than the 21% noticed in low-risk patients.Conclusions:Genetic polymorphisms in COX-2/PGE2 pathway appear to contribute to the development of colorectal adenomas and influence the interval time to adenomas recurrence. The definition of risk models through the inclusion of genetic biomarkers might improve the adherence and optimization of current screening and surveillance guidelines for colorectal cancer prevention.

COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data.

BackgroundNumerous case–control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (−765G > C), rs689466 (−1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association.MethodsWe searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software.ResultsFinally 8 case–control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data.ConclusionCurrent results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association.

Influence of the Cyclooxygenase-2 Gene -765G/C and -1195G/A Polymorphisms on Development of Ischemic Stroke

Many studies have investigated the association between the cyclooxygenase-2 (COX-2) gene polymorphism and ischemic stroke. However, results of these studies still remain controversial. To better explain the association between COX-2 polymorphisms (-765G/C and -1195G/A) and ischemic stroke risk, a meta-analysis was performed. Relevant studies were identified from 4 Chinese databases (Chinese Biological Medical Literature database, Chinese National Knowledge Infrastructure database, Chongqing VIP database, and Chinese WANFANG database), PUBMED and EMBASE prior to December 2015. The strength of association between COX-2 polymorphism and ischemic stroke was evaluated by the odds ratio (OR) with 95% confidence interval (CI). Inconsistency index (I(2)) and the Cochran's Q statistic were used to check heterogeneity. Publication bias was evaluated by funnel plots and Egger's regression test. A total of 4086 ischemic stroke cases and 4747 controls were identified. Significant association between COX-2 -765G/C polymorphism and the risk of ischemic stroke was found in Brazilians and the African-Americans. The OR of (CC+GC versus GG) for the Brazilians and African-Americans were (6.328, 95% CI = 2.295-17.448) and (1.644, 95% CI = 1.060-2.551). In addition, the recessive model of the Brazilians gave an OR of 3.621 (95% CI: 1.519-8.630). Furthermore, the (GC versus GG) and the allele model of the African-Americans were (OR: 1.615, 95% CI = 1.015-2.572) and (OR: 1.422, 95% CI = 1.033-1.957). Significant association was also observed for COX-2 -1195G/A polymorphism in the subtypes of small vessel disease (SVD) of ischemic stroke. Our study suggests that COX-2 -765G/C and -1195G/A polymorphisms may contribute to susceptibility of ischemic stroke, specifically in Brazilians and the African-Americans, and those of SVD.

Modification of the association of bisphenol A with abnormal liver function by polymorphisms of oxidative stress-related genes

Some studies suggested oxidative stress as a possible mechanism for the relation between exposure to bisphenol A (BPA) and liver damage. Therefore, we evaluated modification of genetic polymorphisms of cyclooxygenase 2 (COX2 or PTGS2), epoxide hydrolase 1 (EPHX1), catalase (CAT), and superoxide dismutase 2 (SOD2 or MnSOD), which are oxidative stress-related genes, on the relation between exposure to BPA and liver function in the elderly. We assessed the association of visit-to-visit variations in BPA exposure with abnormal liver function by each genotype or haplotype after controlling for age, sex, BMI, alcohol consumption, exercise, urinary cotinine levels, and low density lipoprotein cholesterol using a GLIMMIX model. A significant association of BPA with abnormal liver function was observed only in participants with COX2 GG genotype at rs5277 (odds ratio (OR)=3.04 and p=0.0231), CAT genotype at rs769218 (OR=4.16 and p=0.0356), CAT CT genotype at rs769217 (OR=4.19 and p=0.0348), SOD2 TT genotype at rs4880 (OR=2.59 and p=0.0438), or SOD2 GG genotype at rs2758331 (OR=2.57 and p=0.0457). Moreover, we also found higher OR values in participants with a pair of G-G haplotypes for COX2 (OR=2.81 and p=0.0384), G-C-A haplotype for EPHX1 (OR=4.63 and p=0.0654), A-T haplotype for CAT (OR=4.48 and p=0.0245), or T-G-A haplotype for SOD2 (OR=2.91 and p=0.0491) compared with those with the other pair of haplotypes for each gene. Furthermore, the risk score composed of 4 risky pair of haplotypes showed interactive effect with BPA on abnormal liver function (p=0.0057). Our study results suggest that genetic polymorphisms of COX2, EPHX1, CAT, and SOD2 modify the association of BPA with liver function.

Cyclooxygenase 2 (rs2745557) Polymorphism and the Susceptibility to Benign Prostate Hyperplasia and Prostate Cancer in Egyptians.

Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression, and metastasis. We aimed to evaluate the association between COX-2 (rs2745557) polymorphism and prostate cancer (PCa), benign prostate hyperplasia (BPH) risk. We also assessed the influence of other risk factors such as obesity, smoking, diabetes in modulating the risk of PCa in Egyptian men. COX-2 (rs2745557) was genotyped in 112 PC patients, 111 BPH and 120 subjects as a control group. COX-2 and PSA levels were measured by ELISA. We found that GG genotype was associated with a 17-fold increased risk for PCa and 20-fold increased the risk for BPH more than AA genotype. Also, G allele carriers of COX-2 were associated with metastatic cancer (OR=1.3, P<0.05) and disease aggressiveness (OR=3.5, P<0.001). The coexistence of obesity, smoking, or diabetes with GG genotype may lead to increasing the risk of developing BPH (OR=3.3, 4, and 2.7, respectively) and of developing PCa (OR=2.9, 4.9, and 3.2, respectively). Our results showed evidence suggesting the involvement of the COX-2 (rs2745557) polymorphism and its protein in PCa or BPH initiation and progression. Also, the coexistence of COX-2 (rs2745557) and obesity, smoking, or diabetes may lead to the development of PCa or BPH.

COX-1 and COX-2 polymorphisms in susceptibility to cerebral palsy in very preterm infants.

Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain. Recent epidemiological and clinical data suggest intrauterine infection/inflammation as the most common cause of preterm delivery and neonatal complications, including CP. Cyclooxygenases are key enzymes in the conversion of arachidonic acid to prostaglandins. The COX family consists of two isoforms, COX-1 and COX-2. In the brain, COX-2 is constitutively expressed at high levels on pyramidal neurons, while COX-1 is predominantly expressed by microglia and can be upregulated in pathological conditions, such as infection, ischemia and traumatic brain injury. Single nucleotide polymorphisms in the COX-1 and COX-2 gene could have profound effects on COX-1 and COX-2 expression and, directly or indirectly, influence the pathogenesis, development and severity of CP. In this study we investigated the association between single nucleotide polymorphisms of the COX-1 and COX-2 gene and susceptibility to cerebral palsy in very preterm infants. The results of our study showed the association between COX-1 high expression genotype (-842 AA) and COX-1 high expression allele -842A and risk of CP in infants with cystic periventricular leucomalacia (cPVL). Our results support an important role of COX-1 enzyme on microglial activation during neuroinflammation resulting in huge neuroinflammatory response and the proinflammatory mediator overproduction, with the serious white matter damage and CP development as a consequence.

Functional polymorphisms of the cyclooxygenase-2 gene and prognosis of hepatocellular carcinoma - a cohort study in Chinese people.

Cyclooxygenase-2 (COX-2) influences carcinogenesis through regulation of angiogenesis, apoptosis, cytokine expression, and immune response suppression. It has been well established that COX-2 is overexpressed in a variety of human cancers, such as hepatocellular carcinoma (HCC). In this study, we aimed to evaluate the association between COX-2 polymorphisms and prognosis of HCC. We genotyped 200 HCC patients of Chinese Han descent for COX-2 gene polymorphisms (-765G>C and -1195G>A) using PCR-RFLP. Data were statistically analyzed using the Kaplan-Meier method and the Cox's proportional hazard regression model. We found that patients with the COX-2 -1195AG and -1195AG + AA genotypes demonstrated significantly decreased disease-free survival (DFS) as compared with those carrying the -1195GG genotype (P < 0.05). However, the COX-2 -765G>C polymorphism was not associated with DFS (P > 0.05). Moreover, by Cox regression analysis, blood alpha fetoprotein ≤400 ng/mL before the operation and the -1195G>A polymorphism were found to be of prognostic significance (P < 0.05), while the -765G>C polymorphism was not (P > 0.05). In summary, post-operation progression of HCC is more likely to occur in patients with the -1195AG genotype and the A allele. On the other hand, the -765G>C polymorphism is not an independent influence factor of HCC prognosis.

Association Between COX-2 Polymorphisms and Lung Cancer Risk.

BackgroundMultiple relevant risk factors for lung cancer have been reported in different populations, but results of previous studies were not consistent. Therefore, a meta-analysis is necessary to summarize these outcomes and reach a relatively comprehensive conclusion.Material/MethodsSTATA 12.0 software was used for all statistical of the relationship between COX-2 polymorphisms and lung cancer risk. Inter-study heterogeneity was examined with the Q statistic (significance level at P<0.1). The publication bias among studies in the meta-analysis was analyzed with Begg’s funnel plot and Egger’s test. Hardy-Weinberg equilibrium was tested in all controls of the studies.ResultsCOX-2 rs20417 polymorphism had a significant association with reduced risk of lung cancer under homozygous and recessive models, and similar results were observed in white and population-based subgroups under 2 and 3 contrasts, respectively. Additionally, rs2066826 polymorphism manifested a strong correlation with increased risk of lung cancer under 5 genetic models.ConclusionsIn COX-2 gene, rs20417 may have a certain relationship with reduced risk of lung cancer, while rs2066826 may increase the risk of lung cancer.

Association between COX-2 gene polymorphisms and risk of hepatocellular carcinoma development: a meta-analysis

ObjectiveTo investigate the association between cyclo-oxygenase-2 (COX-2) polymorphism and the risk of hepatocellular carcinoma (HCC) development.DesignSystematic review and meta-analysis of COX-2 polymorphism and risk of HCC development among people with...

Retraction Note to: Relationships of COX2 and MMP12 genetic polymorphisms with chronic obstructive pulmonary disease risk: a meta-analysis.

We performed the present meta-analysis in an attempt to confirm the correlation of genetic polymorphisms in the COX2 and MMP12 genes with the susceptibility to chronic obstructive pulmonary disease (COPD). We searched English database such as PubMed, CISCOM, CINAHL, Web of Science, Google Scholar and several Chinese database for meta-analysis. There were no specific language restrictions. Two investigators systematically extracted relevant data within those included studies. Crude ORs with its corresponding 95 % CI were calculated. STATA 12.0 software was adopted for statistical analysis. The impact of COX2 and MMP12 genetic polymorphisms on the pathogenesis of COPD was investigated in the current study with a total of 10 case–control studies, which includes 1,751 COPD patients and 2,472 healthy subjects. Four common polymorphisms, including rs689466 G > A and rs20417 G > C in the COX2 gene, rs652438 A > G and rs2276109 A > G were evaluated in the MMP12 gene. Pooled OR of the present studies and results showed that the frequency of COX2 rs20417 polymorphism was prevalent in COPD patients than those of healthy subjects (C allele vs. G allele OR = 1.33, 95 % CI 1.06–1.67, P = 0.014; GC + CC vs. GG OR = 1.86, 95 % CI 1.07–3.24, P = 0.029; respectively). However, we found no significant correlation between COX2 rs689466 polymorphism and the risk of COPD (all P > 0.05). Furthermore, our meta-analysis illustrated that individuals with MMP12 rs652438 polymorphism had significantly increased risk of developing COPD (G allele vs. A allele OR = 1.62, 95 % CI 1.08–2.42, P = 0.020; AG + GG vs. AA OR = 2.14, 95 % CI 1.12–4.09, P = 0.021; respectively). Nevertheless, no positive relation was detected between MMP12 rs2276109 variant and the risk of COPD. Our meta-analysis indicates that COX2 and MMP12 genetic polymorphisms may be strongly implicated in the development of COPD, especially for the COX2 rs20417 and MMP12 rs652438 polymorphisms. Thus, COX2 and MMP12 genetic polymorphisms could potentially be utilized as helpful biomarkers for early diagnosis of COPD.

Cyclooxygenase-2 gene polymorphisms and the risk of colorectal cancer: A population-based study.

The aim of the present study was to determine the association between polymorphisms in the cyclooxygenase-2 (COX-2) gene promoter region, rs20417 G/C and rs2745557 G/A, and the susceptibility to colorectal cancer (CRC) in a Han Chinese population in Shaanxi, China. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to detect the polymorphisms of COX-2, rs20417 G/C and rs2745557 G/A, in 300 patients with CRC and 300 healthy individuals in the present case-control study. The results revealed that for the COX-2 rs20417 G/C polymorphism, the GC+CC allele frequency was 80% in CRC patients and 71% in healthy controls [odds ratio (OR)=1.63; 95% confidence interval (CI), 1.12-2.38; P=0.01]. For the COX-2 rs2745557 G/A polymorphism, the GA+AA allele frequency was 84% in CRC patients and 73% in healthy controls (OR=1.94; 95% CI, 1.30-2.90; P<0.01). In addition, among individuals with a smoking history, drinking history or family history of CRC, those who were COX-2 rs20417 (GC+CC) or COX-2 rs2745557 (GA+AA) carriers had a significantly increased risk of developing CRC compared with that of GG genotype carriers (P<0.05). Furthermore, the allelic frequencies of COX-2 rs20417 G/C and rs2745557 G/A in patients with lymph node metastasis in stage III/IV of CRC were significantly different from those of COX-2 rs20417 G/C and rs2745557 G/A in patients without lymph node metastasis in stage I/II (P<0.05). In conclusion, the results of the present study revealed that COX-2 rs20417 C allele carriers and rs2745557 A allele carriers have a significantly increased risk of CRC compared with GG genotype carriers; in addition, the frequencies of these alleles were demonstrated to be associated with lymph node metastasis and CRC progression.

The VEGFR2, COX-2 and MMP-2 polymorphisms are associated with clinical outcome of patients with inoperable non-small cell lung cancer.

Certain common inherited variations in genes involved in tumor angiogenesis, progression and metastasis may contribute to cancer therapy outcome and prognosis by altering the gene expression and protein activity. In this report, we examined the effect of functional polymorphisms in MMP-1, MMP-2, MMP-3, VEGF, VEGFR2, FGFR4 and COX-2 genes on overall (OS) and progression-free survival (PFS) of 350 Caucasian patients with inoperable non-small cell lung cancer (NSCLC). The results of multivariate analysis indicated that VEGFR2 -906C and COX-2 -1195G alleles were strongly associated with poor OS and PFS (p = 0.002 and 0.015, respectively, for OS; p = 0.009 and 0.015, respectively, for PFS), while MMP-2 -1306 T allele carriers had significantly reduced PFS (p = 0.010). Moreover, an increased risk of death and progression was significantly associated with the number of adverse alleles for VEGFR2/COX-2 (p = 0.0005 for OS and 0.0006 for PFS in >1 adverse allele carriers) and VEGFR2/COX-2/MMP-2 combinations (p = 0.0003 for OS and 0.0001 for PFS in patients with >2 adverse alleles). Finally, VEGFR2 TC/CC, COX-2 AG/GG and MMP-2 CT/TT genotypes as well as "at risk" allele combinations were identified as independent predictors of unfavorable OS and PFS in the group. In conclusion, the data suggest that selected VEGFR2, COX-2 and MMP-2 polymorphisms may be potential prognostic markers in unresectable NSCLC treated with radiotherapy with or without chemotherapy, although further validation studies are warranted to confirm our observations.