Association of two obesity-related gene polymorphisms LEPG2548A rs7799039 and LEPRQ223R rs1137101 with the risk of breast cancer

Many studies have been performed to investigate the correlation of leptin (LEP) and leptin receptor (LEPR) polymorphisms with breast cancer (BC) risk, however the results are inconclusive. To obtain a more precise estimation, we conducted this meta-analysis. We searched PubMed, EMBASE, and Web of Science databases to identify qualified studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association. Eight eligible studies (2,124 cases and 5,476 controls) for LEP G2548A (rs7799039) polymorphism, and thirteen studies (5,282 cases and 6,140 controls) for LEPR Q223R (rs1137101) polymorphism were included in our study. In general, no significant association between LEP G2548A polymorphism and BC susceptibility was found among five genetic models. In the stratified analysis by ethnicity and sources of controls, significant associations were still not detected in all genetic models. For LEPR Q223R polymorphism, we observed that the association was only statistically significant in Asians (G versus A: OR = 0.532, P = 0.009; GG versus AA: OR = 0.233, P = 0.002; GA versus AA: OR = 0.294, P = 0.006; GG versus AA+AG: OR = 0.635, P = 0; GA+GG versus AA: OR = 0.242, P = 0.003), but not in general populations and Caucasians. In conclusion, LEP G2548A polymorphism has no relationship with BC susceptibility, while LEPR Q223R polymorphism could decrease BC risk in Asians, but not in overall individuals and Caucasians. More multicenter studies with larger sample sizes are required for further investigation.