Cyclooxygenase-2 Gene Polymorphisms Research Articles

Cyclooxygenase-2 (COX-2) gene polymorphism in patients with differentiated thyroid carcinomas in the Turkish population

Background/aim: The most common thyroid malignancies are papillary and follicular thyroid carcinomas. They account for approximately 85%-90% of all thyroid cancers. Recent studies have reported the relevance of cyclooxygenase-2 (COX-2) gene polymorphism in human carcinogenesis. The aim of this study was to investigate the relationship between thyroid carcinoma and COX-2 gene polymorphism in the Turkish population.Materials and methods: We included a total of 96 differentiated thyroid cancer patients (mean age: 46.9 ± 10.3 years; 14 males, 82 females) and 83 healthy control subjects (mean age: 46.0 ± 10.6 years; 39 males, 44 females). The frequency of -765G>C, -8473T>C, and 1195A>G gene polymorphisms in the COX-2 promoter region was investigated in thyroid cancer patients and the control group using the high-resolution melting method. Results: COX-2-765G>C and COX-2-1195A>G gene polymorphisms were similar between thyroid cancer patients and the control group. There was a statistically significant difference between COX-2-8473T>C gene polymorphism in the thyroid cancer group and the control group (P = 0.012).Conclusion: The single nucleotide gene polymorphism COX-2-8473T>C might contribute to genetic susceptibility to differentiated thyroid cancer in the Turkish population.

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.

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.

Cyclooxygenase-2 gene polymorphisms and risk of Alzheimer's disease: A meta-analysis

PurposeCyclooxygenase-2 (COX-2) is one of the key enzymes in the synthesis of prostaglandins, and plays a pivotal role in inflammatory response. Recent studies have suggested cyclooxygenase-2 is involved in the pathogenesis of Alzheimer's disease (AD). However, the relationship between COX-2 gene polymorphisms (−765G>C rs20417, −1195A>G rs689466) and Alzheimer's disease risk is not conclusive. We conducted a meta-analysis to systematically examine and to clarify the association between the two SNPs and AD risk. MethodsPubMed, EMBASE, Web of Science, Cochrane Library and CBMdisc were searched in July 2015 to identify eligible studies. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. ResultsA total of 7 case–control studies about COX-2 rs20417 polymorphisms and AD risk, and 3 studies about COX-2 rs689466 and AD risk were included in this meta-analysis. For rs20417 (−765G>C), there was a significant association between rs20417 and AD, and the risk for AD decreased in all gene models (C allele versus G allele: OR=0.570 CI 0.484−0.672; CC+GC versus GG: OR=0.568 CI 0.470–0.686; CC versus GC+GG: OR=0.357, CI 0.217–0.587; CC versus GG: OR=0.311, CI 0.189–0.514; GC versus GG: OR=0.613 CI 0.503–0.746). ConclusionC-allele of rs20417 (−765G>C) polymorphism was associated with reduced risk of AD, and might be a protective factor. Because of the limit sample and heterogeneity, the association between rs689466 polymorphism and AD risk should be treated with caution. To further confirm this relationship, larger-scale and better-designed studies should be conducted in the future.

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...

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.

Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

Genetic variation in COX-2 -1195 and the risk of endometriosis and adenomyosis

Aim: This study aims to explore the relationship between COX-2 gene polymorphism and the hereditary susceptibility of endometriosisand adenomyosis. Materials and Methods: Gene polymorphism in COX-2 gene was genotyped in 170 cases of endometriosis, 150 cases of adenomyosis, and 240 matched non-endometriosis and non-adenomyosis controls. Results: Genotypic frequencies of GG, AG, and AA in COX-2 locus in endometriosis and adenomyosis were 16.5%, 51.2%, 32.4% and 16.0%, 49.3%, 34.7%, respectively. They were bothsignificantly different from those in the control group (24.6%, 53.3%, and 22.1%) (p Conclusion: Genetic variation of G to A at -1195 locus in the promoter region of COX-2 gene increases the risk of endometriosis and adenomyosis, and the genetic susceptibility of these two diseases are similar.

Cyclooxygenase-2 (COX2) gene polymorphisms and the risk of sporadic colorectal cancer and polyps among Jordanian population.

Cyclooxygenase-2 (COX2) is a crucial enzyme involved in the metabolism of Prostaglandins and it has been implicated in several processes. This study was done to investigate the associations of polymorphisms in COX2 gene with the risk of colorectal cancer or polyps development among Jordanian population and to correlate with other ethnicities. One hundred and thirty five cases (135) of colorectal carcinoma were studied for COX2 -A1195G polymorphisms employing PCR-RFLP technique, in addition to 104 cases of adenomatous polyps and 115 matched controls taken from the general population. Sixty eight colorectal cancer patients were males and 67 of patients were females with a median age of (58.0±13.9 year). Sixty six (66) of polyp cases were males and 38 were females with a median age of (58.1±14.16). The A-1195G AA carriers were 3.1 times less likely to develop CRC (95% CI: 1.8-5.3, p<0.0001), and 1.8 times less likely to develop polyps (95% CI: 0.99-3.2, p=0.056).The A-1195G AG carriers were at higher risk to develop cancer in a dose dependent manner. The AG carriers were 2.9 time more likely to develop CRC and two times more likely to develop polyps when compared to controls. The A allele was more predominant in controls than in polyps or CRC cases. Carriers of the A allele were 1.6 times less likely to develop polyps and 2.6 times less likely to develop CRC. The presence of the COX-2 -1195AA genotype may protect against risk of developing colorectal cancer.

A Cyclooxygenase 2 Gene Polymorphism is a Risk Factor for the Complication of Medication Overuse Headaches in Patients with Migraines

We determined whether cyclooxygenase-2 (COX-2) gene polymorphisms were involved in the aggravation of migraines due to the overuse of medication. Polymorphisms in the COX-2 (rs20417, rs689466) gene were examined. Forty-seven patients with migraine (6 males and 41 females; 5 with migraines with aura (MA), 36 with migraines without aura (MO), 6 with MA + MO; 1 with MA and 21 with MO; 36.4 ± 10.3 years) and 22 patients with medication overuse headache (MOH) (1 male and 21 females; 39.6 ± 9.9 years) who had migraines participated in this study. The genotypes of each polymorphism were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods. No significant differences were observed in the genotypic distributions of rs20417 (C/C + G/C vs. G/G, p=0.220) between migraine patients and MOH patients. The frequencies of the rs689466 G/G genotype were significantly higher in patients with MOH than in patients with migraines (G/G vs. A/A+A/G, p=0.008). Furthermore, the frequencies of the rs689466 G/G genotype were significantly higher in patients with MOH who had migraines without aura (MO) than in patients with MO (G/G vs. A/A+A/G, p=0.001). The results of this study showed that the COX-2 polymorphism (rs689466) was independently related with the complication of MOH in patients with MO.

Five COX-2 gene polymorphisms and risk of breast cancer: an updated meta-analysis based on 19 case-control studies.

The correlationship between COX-2 gene polymorphisms and breast cancer has been wildly studied, but the results remain controversial. Hence, the present meta-analysis aimed to investigate the association between COX-2 SNPs (rs5275, rs20417, rs689466, rs5277, rs2206593) and risk of breast cancer. Data were collected from PubMed, Embase and China National Knowledge Infrastructure. Summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity test, sensitivity analysis and publication bias test were also performed. There were 17 articles that contained 19 studies in this research. Fourteen case-control studies with 15,007 breast cancer cases and 20,005 controls were concerning rs5275 polymorphism, and 8 case-control studies with 10,216 cases and 12,839 controls were about rs20417 polymorphism. Other three polymorphisms (rs689466, rs2206593, rs5277) were studied in 5, 3 and 3 studies, respectively. COX-2-rs20417 CC genotype was significantly associated with increased risk of breast cancer when comparing to G allele [ORs were 1.231 (1.050-1.444) for CC vs. GG, P=0.01, 1.223 (1.045-1.432) for CC vs. G carrier, P=0.01]. Furthermore, the results of the subgroup analysis by ethnicity suggested that C allele significantly contributed to the risk of breast cancer for Asians [1.459 (1.182-1.802) for GC vs. GG, 1.472 (1.201-1.805) for C carrier vs. GG]. However, no association was found for rs5275, rs689466, rs5277 and rs2206593 in all comparison modes. This meta-analysis indicated that the COX-2 rs20417 polymorphism contributed to genetic susceptibility of breast cancer. In contrast, COX-2 rs5275, rs689466, rs2206593 and rs5277 polymorphisms might be not associated with the risk of breast cancer.

Prognostic value of cyclooxygenase-2 gene polymorphisms in advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy.

Cyclooxygenase-2 (COX-2) plays an important role in cell apoptosis, angiogenesis and tumor invasion, and over-expression of COX-2 is associated with tumor development and occurrence. The aim of this study is to investigate the association between COX-2 polymorphisms and clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy. A total of 190 patients with IIIB or IV NSCLC who received platinum-based chemotherapy were recruited in this study. Four functional COX-2 polymorphisms, including rs689465, rs689466, rs3218625 and rs20417, were genotyped by PCR-based restriction fragment length polymorphism methods. Kaplan-Meier methods were used to compare survival by different genotypes. Cox proportional hazard models were used to identify independently significant variables. The rs689465 AA genotype was significantly associated with longer overall survival (OS) (13.0 months vs 8.8 months, P = 0.019 for log-rank test; hazard ratio [HR] 0.624; 95% confidence internal [CI] 0.418-0.931) and progression-free survival (5.3 months vs 4.0 months, P = 0.018 for log-rank test; HR 0.627; 95% CI 0.421-0.934) compared with AG or GG genotype, especially in patients with adenocarcinoma (P = 0.002), performance status of 1 (P = 0.009) and stage IV disease (P = 0.012), and treated with gemcitabine-based chemotherapy (P = 0.012). Multivariate regression analysis showed that COX-2 rs689465 polymorphism had a significantly independent prognostic value for OS (P = 0.017, HR = 1.637, 95% CI = 1.093-2.453). Our study suggested that rs689465 polymorphism could be a prognostic biomarker for advanced NSCLC patients treated with first-line platinum-based chemotherapy.

Polymorphisms in cyclooxygenase-2 gene and risk of developing coal workers' pneumoconiosis: a case-control study.

Coal workers' pneumoconiosis (CWP) is characterized by progressive pulmonary fibrosis. Inflammation is crucial in the host response to silica and it contributes to pulmonary fibrosis. Cyclooxygenase-2 is involved in this process. The association between single-nucleotide polymorphisms in cyclooxygenase-2 gene with pneumoconiosis risk was investigated. An association study was conducted by analyzing two single-nucleotide polymorphisms of cyclooxygenase-2 (rs689466 and rs20417) in a case-control study involving 90 patients and 90 healthy individuals (controls). Genotyping was performed by the TaqMan method. The rs689466 AG and GG and rs689466 GC polymorphisms were significantly less frequent in patients than in controls. Cyclooxygenase-2 rs689466 and rs20417 variant genotypes exhibited 21% and 12% decreased CWP risk, respectively. Cyclooxygenase-2 rs689466 and rs20417 polymorphisms were associated with CWP risk.

-765 g>c polymorphism of the cox-2 gene and gastric cancer risk in Brazilian population.

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. To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. 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. 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. 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.

Mo1793 Analysis of the Cyclooxygenase-2 (COX-2) and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms in Esophageal Cancer

Mo1793 Analysis of the Cyclooxygenase-2 (COX-2) and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms in Esophageal Cancer

The prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/ COX2) rs5277 polymorphism does not influence risk of colorectal cancer in an Iranian population.

The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue and involved in the synthesis of prostaglandins and thromboxanes, regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have a risk-modifying effect on sporadic colorectal cancer in an Iranian population. We conducted a case-control study on 167 patients with colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran, Iran, between 2007 and 2011. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the COX-2 gene polymorphism (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing. Logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). There was no significant difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the allelic form, among CRC patients compared with the healthy control group (p: 0.867). Our results suggest that rs5277 polymorphism in COX2 could not be a good prognostic indicator for patients with CRC.

Association between cyclooxygenase-2 gene polymorphisms and risk of periodontitis: a meta-analysis involving 5653 individuals

There -765G > C, -1195G > A, and 8473T > C polymorphisms in cyclooxygenase-2 (COX-2) gene polymorphisms and periodontitis risk were investigated based on published studies; however, their results could not give a conclusive result. Hence, we performed this meta-analysis of six published studies with eight case-control studies including these three polymorphisms which searched from PubMed and Web of Science up to October 15th, 2013. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the three polymorphisms of COX-2 and periodontitis risk. The results from 2,580 periodontitis patients and 3,073 healthy controls showed that none of -765G > C, -1195G > A, or 8473T > C polymorphism was not associated with periodontitis susceptibility [Take -765G > C for example: OR = 0.94, 95% CI = (0.57-1.53) for C vs. G; OR = 2.34, 95% CI = (0.72-7.62) for CC vs. GG; OR = 0.68, 95% CI = (0.46-1.01) for CG vs. GG; OR = 0.81, 95% CI = (0.52-1.27) for (CG+GG) vs. GG; OR = 2.57, 95% CI = (0.80-8.29) for CC vs. (GG+CG)]. In subgroup analyses according to the type of periodontitis and ethnicity for -765G > C and -1195G > A, and deviations in Hardy-Weinberg equilibrium for -765G > C, we only observe a boundary association between -1195G > A polymorphism and Asian population. However, due to limitations of this meta-analysis, the results should treat with caution and we suggest the further researches should be carried out to verify our results.

Association Between Cyclooxygenase-2 Gene Polymorphisms and Head and Neck Squamous Cell Carcinoma Risk

Cyclooxygenase-2 (COX-2) is an inducible enzyme that catalyzes prostaglandins through inflammatory response, which may be involved in autoimmune diseases and cancer pathogenesis. Two potentially functional genetic single-nucleotide polymorphisms (COX-2 -1195G>A and 8473T>C) were supposed to contribute to head and neck squamous cell carcinoma (HNSCC) susceptibility. The aim of this study was to determine the association of these polymorphisms with HNSCC susceptibility in a Chinese Han population. In this study, 2 SNPs were genotyped by TaqMan methods in a patient-control study including 260 patients with HNSCC and 1047 cancer-free controls in a Chinese Han population. We found significant difference in the frequency of alcohol consumption between the patients with HNSCC and controls (P < 0.001), but the genotype frequencies of the 2 polymorphisms were not significantly different between the patients and controls. Further stratified analysis indicated that none of the genotypes were associated with increased risk for HNSCC. This research indicated that the COX-2 -1195G>A and 8473T>C polymorphisms may not be involved in the development of HNSCC in the Chinese Han population. However, further perspective studies are warranted to test these findings and further investigate the potential interactions involving the COX-2 polymorphism and HNSCC.

“Letter to editor” in lieu of article published in Mol Biol Rep. 2012 May; 39(5):5219–24. PTGS2 (COX2) −765G&gt;C gene polymorphism and risk of sporadic colorectal cancer in Iranian population

Dear Editor Recently, I read an article with great interest published by Daraei et al., which was appeared in your journal as Daraei et al., 2012 (May; 39(5):5219–5224). The study aimed to evaluate the impact of the COX2 gene -765 G[C polymorphism on sporadic colorectal cancer risk. Though, the study provides preliminary evidence to consider COX2 polymorphism as a risk factor for sporadic colorectal cancer. But, after careful reading of the article, few important issues came out which must be addressed for further actions. First, it appears that the authors somehow missed the statistical power in this study. Sample sizes remain a major issue in genetic case–control studies analyzing the association of polymorphism with disease susceptibility. Hence, the study should obtain an adequate statistical power to estimate significant association accurately, which remains a primary criterion to perform such studies. Underpowered studies usually lead to false positive associations and misinterpretations [1]. The authors failed to mention the incidence rate of sporadic colorectal cancer in the said study. The number of patients and controls recruited in the present study achieved the required statistical power is questionable and did not discuss in the text. Second, in Table 2, the percentage of genotype did not reveal 100 % in sporadic colorectal cancer patients. All these points suggest a thorough examination of the association observed in the said study, and must be clarified before concluding that COX2 gene polymorphism is a potential marker of sporadic colorectal cancer.

Cyclooxygenase-2 169C > G and 8473T > C gene polymorphisms and prostaglandin E2 level in breast cancer: A case–control study

AimsCyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) is linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C>G and 8473T>C gene polymorphisms and PGE2 level at various stages of BC clarifying the role of COX-2 gene polymorphism and PGE2 in relation to BC. MethodsThe study population comprised 160 women at different stages of BC and 150 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by ELISA, the COX-2 gene polymorphisms were determined using PCR-RFLP. ResultsThe variant alleles COX-2 169G and 8473C were significantly associated with BC susceptibility [OR=3.1, 95% CI (2.2–4.4), P<0.001 for 169C>G and OR=1.74, 95%CI (1.3–2.4), P=0.005 for 8473C]. However, both COX-2 gene polymorphisms were not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In early and late stages of BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P<0.001) for 169 C>G, also towards the presence of CC than TT (P<0.001) for 8473T>C SNP. ConclusionThe 169C>G and 8473T>C polymorphisms of the COX-2 gene were associated with the BC in Egyptian women. Furthermore, individuals with COX-2 169GG and 8473CC genotypes showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.