Cyclooxygenase-2 Polymorphisms and Susceptibility to Esophageal Cancer: a Meta-analysis

Esophageal cancer (EC) is one of the most common cancers worldwide with 5-year survival rate less than 10%. However, there is a lack of specific genetic markers that could help better understanding the mechanisms of esophageal carcinogenesis, improving the detection rate of EC, and distinguishing histological types. Cyclooxygenase-2 (COX-2) as an inducible enzyme in cancer development and progression is involved in esophageal carcinogenesis. A large number of studies have demonstrated a strong association between COX-2 polymorphisms and EC risk. However, the overall results are still controversial. This controversy may be partly due to the mix-up of esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). The aim of this study was to investigate the association between COX-2 polymorphisms and susceptibility to ESCC or EAC by conducting a meta-analysis. Seven studies were retrieved reporting a total of 1450 ESCC patients, 523 EAC patients, and 2663 cancer-free control subjects. Five COX-2 polymorphisms were addressed, including -765G>C (rs20417), -1195G>A (rs689465), -1290A>G (rs689466), -8473T>C (rs5275) and -1759G>A (rs3218625). Meta-analysis results showed that the -765C allele is significantly associated with the susceptibility to both ESCC and EAC especially in Asian populations. In addition, there was a significant association between the -8473C allele and the susceptibility to EAC in Caucasian populations. In conclusion, our meta-analysis suggests that the -765C allele of the COX-2 gene might be a potential risk factor for both ESCC and EAC especially in Asian populations, while the -8473C allele might be a risk factor for EAC in Caucasian populations.