The relationship between apolipoprotein E gene ε2/ε3/ε4 polymorphism and breast cancer risk: a systematic review and meta-analysis

OBJECTIVE: We conducted a systematic review and meta-analysis aiming to assess the relationship between apolipoprotein E (APOE) gene ε2/ε3/ε4 polymorphism and breast cancer risk. METHODS: Yun-Long Liu and Hao-Min Zhang independently completed literature retrieval and data collection, and statistical analyses were performed by Stata. Individual odds ratio (OR) and 95% confidence interval (CI) were pooled in a random-effects model using the DerSimonian–Laird method. Heterogeneity was evaluated by I(2) statistic at a significance level of 50%. Publication bias was assessed by Egger’s test. RESULTS: Eleven articles including 2,074 breast cancer patients and 2,372 controls were summarized. Using the most common allele ε3 as a reference, the ε2 (OR =0.87, 95% CI =0.72–1.05, P=0.154, I(2)=0.0%) and ε4 (OR =1.07, 95% CI =0.80–1.42, P=0.654, I(2)=71.8%) alleles were not found to be significantly associated with breast cancer risk in the overall analyses. Subgroup analyses revealed that the comparison of allele ε4 with ε3 was significant in Asians (OR =1.58, 95% CI =1.17–6.32, P=0.003, I(2)=12.1%) and in studies that used the restriction fragment length polymorphism (RFLP) genotyping method (OR =1.27; 95% CI =1.01–1.61, P=0.045, I(2)=34.3%), and was marginally significant in hospital-based studies (OR =1.33; 95% CI =0.98–1.79, P=0.065, I(2)=30.2%), without heterogeneity. Moreover, the presence of the ε2 allele was significantly associated with breast cancer in small studies (total sample size <500) (OR =0.73, 95% CI =0.54–1.00, P=0.052, I(2)=0.0%) without heterogeneity. The Egger’s test indicated low probabilities of publication bias. CONCLUSION: We observed a significant association between APOE gene ε4 allele and breast cancer risk in Asian populations. Moreover, the findings of our subgroup analyses suggest that source of controls, genotyping platform, and sample size might be the potential causes of heterogeneity.