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

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.

<p>Leptin rs7799039 (G2548A) polymorphism is associated with cancer risk: a meta-analysis involving 25,799 subjects</p>

“…Based on the selection criteria, 30 publications focusing on the association of the LEP rs7799039 G>A polymorphism with cancer risk were included 21,26–53. One publication contained two independent case–control studies that we treated as two investigations 49.…”

“…A total of 31 case–control studies involving 25,799 subjects were included in this meta-analysis. Among them, 19 were conducted in Caucasians,26–44 eight performed in Asians,21,45–50,54 and four were in mixed populations 51–53. Nine were population-based,27,28,30,33,37,38,43,44,50 and 22 case–control were hospital-based studies 21,26,29,31,32,34–36,39–42,45–49,51–54.…”

“…Nine were population-based,27,28,30,33,37,38,43,44,50 and 22 case–control were hospital-based studies 21,26,29,31,32,34–36,39–42,45–49,51–54. Of all the eligible studies, 11 focused on breast cancer,33,37–40,44,48,49,51,53 four focused on colorectal cancer (CRC),31,32,41,52 three focused on prostate cancer (PC),26,30,34 and 13 focused on other cancers 21,27–29,35,36,42,43,45–47,50,54. Other information includingd case–control studies in the pooled analysis is summarized in Table 1.…”

Signaling Pathways Induced by Leptin during Epithelial–Mesenchymal Transition in Breast Cancer

“…Likewise, the A allele of LEP G2548A is associated with the size of the tumor [ 137 ]. Interestingly, the LEP G2548A polymorphism is related to variations in the levels of leptin in serum; however, this polymorphism was not related to the susceptibility to develop breast cancer [ 138 , 139 ]. On the other hand, the LEPR Q223R polymorphism, involved in receptor functionality, was shown to decrease the risk of developing breast cancer in Asian women but not in Caucasian women [ 138 ].…”

“…Interestingly, the LEP G2548A polymorphism is related to variations in the levels of leptin in serum; however, this polymorphism was not related to the susceptibility to develop breast cancer [ 138 , 139 ]. On the other hand, the LEPR Q223R polymorphism, involved in receptor functionality, was shown to decrease the risk of developing breast cancer in Asian women but not in Caucasian women [ 138 ]. A study of Iranian women with breast cancer showed a higher frequency of breast cancer development associated with the LEP G2548A polymorphism of the A allele, as compared to the control group; interestingly, the polymorphism of the G allele conferred a protective phenotype [ 140 ].…”