Abstract
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.
Highlights
Breast cancer is a complex and heterogeneous disease and has become a challenging health issue confronted by women worldwide [1, 2]
Eight eligible studies about LEP G2548A polymorphism and thirteen articles about LEPRQ223R polymorphism were included in our metaanalysis
In the subgroup analysis by ethnicity, we found leptin receptor (LEPR) Q223R polymorphism was associated with a decreased risk of breast cancer (BC) among Asians under the five genetic models: G versus A (OR = 0.532, 95% confidence intervals (CIs) = 0.311-0.856, P = 0.009), GG versus AA (OR = 0.233, 95% CI = 0.092–0.59, P = 0.002), GA versus AA (OR = 0.294, 95% CI = 0.124–0.699, P = 0.006), GG versus AA+AG (OR = 0.635, 95% CI = 0.521–0.787, P < 0.001) and GA+GG versus AA (OR = 0.242, 95% CI = 0.097–0.607, P = 0.003), while no meaningful correlation was observed in Caucasians
Summary
Breast cancer is a complex and heterogeneous disease and has become a challenging health issue confronted by women worldwide [1, 2]. Several published studies have shown that leptin can regulate endothelial cell proliferation and promote angiogenesis; it has an association with www.impactjournals.com/oncotarget progression and poor survival of BC [9, 10, 11]. Leptin exerts it physiological action through the leptin receptor which is overexpressed in BC [12]. Genetic variations in some obesity-related genes have been demonstrated to affect BC risk by the levels and functioning of leptin [13, 14, 15]. LEPR Q223R polymorphism alters amino acid change from neutral to positive that could affect the functionality of the receptor and modifies its signaling capacity [18, 19]
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