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

Authors Liu Y, Zhang H, Pan H, Bao Y, Xue J, Wang T, Dong X, Li X, Bao H

Received 11 August 2015

Accepted for publication 21 November 2015

Published 7 March 2016 Volume 2016:9 Pages 1241—1249

DOI https://doi.org/10.2147/OTT.S94228

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Yun-Long Liu,1 Hao-Min Zhang,1 Hong-Ming Pan,2 Yu-Hang Bao,2 Jing Xue,2 Tian-Chang Wang,1 Xiao-Cheng Dong,1 Xiao-Ling Li,3 Hong-Guang Bao1

1Department of Chest Surgery, The Second Affiliated Hospital of Qiqihar Medical University, 2Basic Medical Science College, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China; 3Department of Anatomy, Basic Medical Science College, Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China

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 I2 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, I2=0.0%) and ε4 (OR =1.07, 95% CI =0.80–1.42, P=0.654, I2=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, I2=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, I2=34.3%), and was marginally significant in hospital-based studies (OR =1.33; 95% CI =0.98–1.79, P=0.065, I2=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, I2=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.

Keywords: apolipoprotein E, breast cancer, polymorphism, meta-analysis

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