-765G>C and 8473T>C polymorphisms of COX-2 and cancer risk: a meta-analysis based on 33 case-control studies.
Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in cancer etiology. The -765G>C and 8473T>C polymorphisms have been implicated in cancer risk. However, the results on the association between the two COX-2 polymorphisms and cancer risk are conflicting. To derive a more precise estimation of the association between them, we performed a meta-analysis of 8,090 cancer cases and 11,010 controls concerning -765G>C polymorphism and 14,283 cancer cases and 15,489 controls concerning 8473T>C polymorphism from 33 case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the -765GC or GC/CC genotypes were associated with higher cancer risk than those with the -765GG genotype and in the stratified analysis this effect maintained in colorectal carcinoma or esophageal cancer of Asian descents. Overall, no significant cancer risk of 8473T>C polymorphism was found. Stratified by cancer types, the variant 8473CC was associated with a decreased risk in breast cancer, compared with the TT or TC/TT genotypes and in lung cancer subgroup after sensitive analysis, there was a decreased risk in CC versus TT, TC versus TT and the dominant models. Moreover, a decreased risk of lung cancer was observed among smokers in the dominant model. In summary, this meta-analysis suggesting that -765G>C may cause an increased risk of colorectal carcinoma and esophageal cancer in Asian descents while 8473T>C polymorphism may cause a decreased risk of breast and lung cancer.
Zhu
Wei
W
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Wei
Bing-bing
BB
Shan
Xia
X
Liu
Ping
P
D000483:Alleles; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004777:Environment; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human