The Cox-2 -1195 G > A polymorphism and cancer risk: a meta-analysis of 25 case-control studies.
ABSTRACT Cyclooxygenase 2 (Cox-2, a rate-limiting enzyme in the conversion of arachidonic acid to prostanoids) has been implicated in several physiological and pathological processes, and it has been reported that polymorphisms in the regulatory region of Cox-2 might influence its expression, contributing to the interindividual susceptibility to cancer. However, results from published studies on the association between the Cox-2 -1195G > A polymorphism and the risk of cancer are conflicting. We performed a meta-analysis based on 25 case-control studies, including a total of 9482 cancer cases and 12 206 controls to derive a more precise estimation of the association and its possible influence on cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results indicated that the variant genotypes moderately increased risk of cancer (AA/AG versus GG, OR = 1.15, 95% CI: 1.02-1.31). In the stratified analysis for the -1195G > A polymorphism, a proximate association was observed in Asian populations (AA/AG versus GG, OR = 1.28, 95% CI: 1.12-1.46), but no significant association except for oesophageal cancer and 'others' was found when stratified by cancer type. In conclusion, our meta-analysis indicates that -1195G > A of Cox-2 is a low penetration risk factor for cancer.
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ABSTRACT: Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandins synthesis which exists in two isoforms, COX-1 and COX-2. Over-expression of COX-2 was considered to increase the proliferation and enhance the invasiveness of breast cancer cells. It was suggested that genetic variations in COX-2 could influence its expression. Herein, the present study was aimed to investigate the associations between two mostly studied functional polymorphisms (-765 G > C and 8473 C > T) in COX-2 and breast cancer risk in Chinese Han women. In the hospital-based case-control study, 465 breast cancer patients and 799 cancer-free controls were genotyped for the COX-2 -765 G > C and 8473 C > T polymorphisms using TaqMan assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using the logistic regression. Compared with the wild genotype of -765 G > C, we found a statistically significant increased risk of breast cancer associated with the variant genotypes [GC/CC vs. GG: OR = 1.56, 95% CI = 1.11-2.21]. In the stratified analysis, the increased risk was more predominant among the subgroups of younger subjects (OR = 1.61, 95% CI = 1.00-2.61). Furthermore, the variant genotypes were associated with large tumor size (OR = 3.01, 95% CI = 1.47-6.12). No significant association was observed for the 8473 C > T polymorphism. Our results suggest that the functional -765 G > C polymorphism in the promoter of COX-2 may influence the susceptibility and progression of breast cancer in the Chinese Han population.Cancer Cell International 05/2014; 14:38. DOI:10.1186/1475-2867-14-38 · 1.99 Impact Factor
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ABSTRACT: Several single nucleotide polymorphisms have been identified in cyclooxygenase-2 (COX-2) genes (e.g., -765 G>C (rs20417), -1195G>A (rs689466), and 8473 C>T (rs5275)). The association of these SNPs with the risk of different cancer types is still controversial. This study aims to evaluate the correlation between these SNPs and breast cancer risk in different ethnic groups. We have searched PubMed, Web of Knowledge, and Embase for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the associations. A total of 13 studies (15,330 cases and 19,260 controls) were eligible for meta-analysis. This meta-analysis showed that COX-2 rs20417 polymorphism was correlated with an increased risk of breast cancer in Caucasians, while rs689466 was associated with a decreased risk of breast cancer in Caucasians. The rs5275 polymorphism had no association with breast cancer risk.Disease markers 08/2014; 2014:484729. DOI:10.1155/2014/484729 · 2.17 Impact Factor
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ABSTRACT: The current meta-analysis incorporating 15 case-control studies involving 4,138 cases and 4,269 controls was performed on the basis of a systematical search in electronic databases for a more precise estimation on the associations of three common polymorphisms -765 G>C (rs20417), -1195G>A (rs689466) and +8473 C>T (rs5275) in Cyclooxygenase-2 (Cox-2) gene with the susceptibility to bladder cancer. The results showed that there was a significant association between rs5275 polymorphism and bladder cancer risk (C vs. T; OR=0.84; CC vs. TT: OR=0.76), especially among Chinese (CC vs. TC+TT: OR=0.48) and American (C vs. T; OR=0.83; TC vs. TT: OR=0.73; CC+TC vs. TT: OR=0.73). and the rs20417 polymorphism was significantly associated with an increased risk of bladder cancer among Chinese (C vs. G: OR=1.46; GC vs. GG: OR=1.49; CC+GC vs. GG: OR=1.51) and Indian (GC vs. GG: OR=1.63; CC+GC vs. GG: OR=1.46), but a reduced risk among American (C vs. G: OR=0.81; GC vs. GG: OR=0.76; CC+GC vs. GG: OR=0.76). Additionally, we found that the rs689466 polymorphism was associated with a decreased risk of bladder cancer in Indian (GA vs. GG: OR=0.68; AA vs. GG: OR=0.39).The present meta-analysis suggests that Cox-2 rs5275 polymorphism may contribute to the risk of bladder cancer, particularly among Chinese and American. The rs20417 polymorphism may play a protective role in the development of bladder cancer in Indian and Chinese but act as a risk factor among American, while the rs689466 polymorphism was more likely to be associated with a decreased risk of bladder cancer in Indian.International Journal of Clinical and Experimental Medicine 01/2015; 8(3):3935-45. · 1.42 Impact Factor