Association between the polymorphisms of urokinase plasminogen activation system and cancer risk: a meta-analysis

PURPOSE The present study aimed to investigate the potential association between the urokinase plasminogen activation (uPA) system polymorphisms (rs4065, rs2227564, and rs344781) and cancer risk. METHODS An extensive search was performed to identify published case-control studies on the association between the uPA system polymorphisms and cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the relationship between the uPA system polymorphisms and cancer risk. RESULTS A total of 20 studies comprising 7,037 cancer cases and 10,094 controls were identified and included in the present meta-analysis. Overall, significantly increased cancer risk was associated with the uPA polymorphism rs4065 (T vs C: OR 1.50, 95% CI: 1.19-1.89; TT vs CC: OR 4.63, 95% CI: 3.10-6.91; dominant model: OR 1.93, 95% CI: 1.60-2.33; recessive model: OR 3.02, 95% CI: 1.26-7.25) and the uPA receptor polymorphism rs344781 (T vs C: OR 1.13, 95% CI: 1.04-1.23; TC vs CC: OR 1.26, 95% CI: 1.06-1.49; TT vs CC: OR 1.35, 95% CI: 1.13-1.63; dominant model: OR 1.29, 95% CI: 1.10-1.52). No significant association was found between the uPA polymorphism rs2227564 and cancer risk. Subgroup analysis suggests that the T allele of the rs4065 (T allele vs C allele: OR 1.50, 95% CI: 1.19-1.89) and rs344781 polymorphisms (T allele vs C allele: OR 1.13, 95% CI: 1.04-1.23) was associated with increased cancer risk in Asians. CONCLUSION Our results suggest that the uPA polymorphism rs4065 and the uPA receptor polymorphism rs344781 are associated with increased cancer risk.