Potentially functional COX-2-1195G>A polymorphism increases the risk of digestive system cancers: a meta-analysis.
OBJECTIVE
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.
Dong
Jing
J
Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China.
Dai
Juncheng
J
Zhang
Mingfeng
M
Hu
Zhibin
Z
Shen
Hongbing
H
D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004067:Digestive System Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity; D020022:Genetic Predisposition to Disease; D014943:Global Health; D006801:Humans; D015994:Incidence; D011110:Polymorphism, Genetic; D012307:Risk Factors
D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2