Potentially functional COX-2-1195G>A polymorphism increases the risk of digestive system cancers: A meta-analysis

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-h (eterogeneity) = 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.