AURKA 基因(rs2273535 和 rs1047972)多态性与乳腺癌风险的关联：一项涉及 37221 例受试者的荟萃分析。
Association between genetic polymorphisms in AURKA (rs2273535 and rs1047972) and breast cancer risk: a meta-analysis involving 37,221 subjects.
机构信息
Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China ; Center for Translational Medicine, Frontier Institute of Science and Technology (FIST), Xi'an Jiaotong University, Xi'an, 710049 China.
Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China.
出版信息
Cancer Cell Int. 2014 Sep 5;14(1):91. doi: 10.1186/s12935-014-0091-y. eCollection 2014.
BACKGROUND
Published data on the association between AURKA polymorphisms and breast cancer (BC) risk are inconclusive. This meta-analysis was performed to derive a more precise estimation on the relationship between AURKA polymorphisms (rs2273535 and rs1047972) and BC risk.
METHODS
PubMed, Web of Knowledge and Embase were searched for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of associations. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed for allele contrast genetic model, homozygous genetic model, heterozygote genetic model, dominant model, and recessive model, respectively.
RESULTS
A total of 13 studies (16,349 BC patients and 20,872 case-free controls) were involved in this meta-analysis. Meta-analysis showed that there was significant association between rs2273535 and BC risk in three genetic models in the overall population (A vs. T: OR = 1.08, 95% CI = 1.01-1.15, P = 0.02; AA vs. TT: OR = 1.36, 95% CI = 1.06-1.73, P < 0.00001; AA vs. TT + TA: OR = 1.15, 95% CI = 1.01-1.31, P = 0.04). In the subgroup analysis by ethnicity, the effects remained in Asians (allele contrast genetic model: OR = 1.12, 95% CI = 1.00-1.26, P = 0.04 and homozygote comparison: OR = 1.22, 95% CI = 1.06-1.41, P = 0.007). However, no genetic models reached statistical association in Cauasians. Rs1047972 polymorphism was associated with BC risk in the overall population based on homozygote comparison (AA vs. GG: OR = 0.81, 95% CI = 0.66-0.99, P = 0.04). When stratified by ethnicity, rs1047972 polymorphism had a decreased association with BC risk in Caucasians based on allele contrast genetic model, homozygote comparison, the dominant model and the recessive model. However, there was no association in any genetic model in Asians.
CONCLUSIONS
This meta-analysis suggests that AURKA rs2273535 polymorphism has an increased risk with BC, especially in Asians. However, rs1047972 polymorphism has a decreased BC risk in Caucasians. Further large scale multicenter epidemiological studies are warranted to confirm this finding.
背景
关于 AURKA 多态性与乳腺癌（BC）风险之间的关联，已有发表的数据尚无定论。本荟萃分析旨在更精确地评估 AURKA 多态性（rs2273535 和 rs1047972）与 BC 风险之间的关系。
方法
检索 PubMed、Web of Knowledge 和 Embase 以获取相关研究。使用优势比（OR）及其 95%置信区间（CI）来估计关联的强度。分别采用等位基因对比遗传模型、纯合遗传模型、杂合遗传模型、显性模型和隐性模型对合并的优势比（OR）及其 95%置信区间（CI）进行计算。
结果
共有 13 项研究（16349 例 BC 患者和 20872 例无病例对照）纳入本荟萃分析。荟萃分析显示，rs2273535 与总体人群中三种遗传模型的 BC 风险存在显著关联（A 对 T：OR=1.08，95%CI=1.01-1.15，P=0.02；AA 对 TT：OR=1.36，95%CI=1.06-1.73，P<0.00001；AA 对 TT+TA：OR=1.15，95%CI=1.01-1.31，P=0.04）。按种族进行亚组分析，结果在亚洲人群中仍然存在（等位基因对比遗传模型：OR=1.12，95%CI=1.00-1.26，P=0.04；纯合比较：OR=1.22，95%CI=1.06-1.41，P=0.007）。然而，在高加索人群中，没有遗传模型达到统计学关联。rs1047972 多态性与总体人群中的 BC 风险相关，基于纯合比较（AA 对 GG：OR=0.81，95%CI=0.66-0.99，P=0.04）。按种族分层后，rs1047972 多态性在高加索人群中与 BC 风险的关联在等位基因对比遗传模型、纯合比较、显性模型和隐性模型中均降低。然而，在亚洲人群中，任何遗传模型均无关联。
结论
本荟萃分析表明，AURKA rs2273535 多态性与 BC 风险增加相关，尤其是在亚洲人群中。然而，rs1047972 多态性与高加索人群中的 BC 风险降低相关。需要进一步的大规模多中心流行病学研究来证实这一发现。
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