Association Of Leptin Receptor Gene Polymorphisms With Risk Of Breast Cancer: A Systematic Review And Meta-analysis

Objective: A lot of epidemiological researches have shown the potential connection between leptin and body fat extent along with breast cancer.Leptin plays its physiological role through the leptin receptor(LEPR).However,published data on the association between LEPR alleles and breast cancer occurrence are conflicting each other.This study systematically evaluated the overall risk of LEPR polymorphisms associated with the risk of breast cancer and provided some guidance for the diagnosis and treatment of breast cancer.Methods: PubMed,PubMed Central,ISI Web of Knowledge,CNKI and Embase databases were searched to identify potentially eligible studies published up to April,20,2012 based on the key words.Eligible studies were enrolled according to the inclusion and exclusion criteria.Meta-analysis was performed by Stata 10.0.The strength of associations between leptin receptor gene polymorphisms and risk of breast and was described as odds ratio(OR)and its 95% confidence intervals(CI).The heterogeneity between studies was assessed by the Q statistic and I-squared tset.The random effects model was selected when there was significant heterogeneity;otherwise,the fixed effects model was used.Potential sources of heterogeneity were explored by subgroup analyses and sensitivity analysis.The publication bias was evaluated by Begg funnel plot and Egger's linear regression test.Results: A total of 10 studies involving 4644 cases and 5485 controls for LEPR rs1137101 polymorphism were enrolled in the meta-analysis.Five studies with 2759 cases and 4464 controls were included in the meta-analysis for rs1137100 polymorphism and 2studies were included for rs8179183,rs4655537,and rs3762274 polymorphisms.Overall,when all studies were conbined in the meta-analysis,a significant association was foundbetween LEPR rs1137101 polymorphism and breast cancer risk in the allele contrast model(OR= 0.71,95%CI= 0.551–0.997).In the subgroup analysis by the variable of ethnicity,Asians showed a higher risk of breast cancer in the allele contrast model(OR= 0.414,95%CI= 0.312–0.550)and dominant model(OR= 0.537,95 % CI 0.370–0.781)and Africans also presented a higher risk of breast cancer in the allele contrast model(OR0.716,95%CI= 0.595–0.861),homozygote codominant(OR= 0.537,95%CI= 0.370–0.781)and dominant model(OR= 1.595,95%CI= 1.207–2.108).And for the LEPR rs1137100 polymorphism,there was a significant higher risk in the allele contrast(OR= 0.666,95%CI= 0.603–0.720)and homozygote codominant models(OR= 0.344,95%CI=0.282–0.421).For LEPR rs8179183,rs4655537,and rs3762274 polymorphisms,no statistically significant correlation was found in all comparison models.Conclusions: This comprehensive meta-analysis indicated that rs1137101 and rs1137100 polymorphisms were significantly associated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant had lower risk of breast cancer.Further,no significant associations were found between LEPR rs8179183,rs4655537,and rs3762274 polymorphisms and risk of breast cancer.