Department of Orthopedics Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
PLoS One. 2013 Sep 6;8(9):e73611. doi: 10.1371/journal.pone.0073611. eCollection 2013.
The association between polymorphisms on 5p12 and breast cancer (BC) has been widely evaluated since it was first identified through genome-wide association approach; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two wildly studied polymorphisms (rs10941679 and rs4415084) on 5p12.
Databases including Pubmed, EMBASE, Web of Science, EBSCO, and Cochrane Library databases were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias.
A total of 19 articles involving 100,083 cases and 163,894 controls were included. An overall random-effects per-allele OR of 1.09 (95% CI: 1.06-1.12; P = 4.5 × 10(-8)) and 1.09 (95% CI: 1.05-1.12; P = 4.2 × 10(-7)) was found for the rs10941679 and rs4415084 polymorphism respectively. Significant results were found in Asians and Caucasians when stratified by ethnicity; whereas no significant associations were found among Africans/African-Americans. Similar results were also observed using dominant or recessive genetic models. In addition, we find both rs4415084 and rs10941679 conferred significantly greater risks of ER-positive breast cancer than of ER-negative tumors.
Our findings demonstrated that rs10941679-G allele and rs4415084-T allele might be risk-conferring factors for the development of breast cancer, especially in Caucasians and East-Asians.
自全基因组关联研究首次发现 5p12 上的多态性与乳腺癌（BC）之间存在关联以来，人们广泛评估了这种关联；然而，这些研究的结果却相互矛盾。我们试图通过对 5p12 上两个广泛研究的多态性（rs10941679 和 rs4415084）进行综合荟萃分析来解决这种不一致性。
我们检索了 Pubmed、EMBASE、Web of Science、EBSCO 和 Cochrane Library 数据库，以查找相关研究。使用优势比（OR）及其 95%置信区间（CI）来评估关联的强度。应用随机效应模型，以解决异质性和发表偏倚。
共纳入 19 项研究，涉及 100083 例病例和 163894 例对照。rs10941679 和 rs4415084 多态性的总体随机效应等位基因 OR 分别为 1.09（95%CI：1.06-1.12；P=4.5×10(-8)）和 1.09（95%CI：1.05-1.12；P=4.2×10(-7)）。按种族分层，在亚洲人和高加索人中发现了显著结果；而在非洲裔/非裔美国人中则没有发现显著关联。在显性或隐性遗传模型中也观察到了相似的结果。此外，我们发现 rs4415084 和 rs10941679 均与 ER 阳性乳腺癌的风险显著增加相关，而非 ER 阴性肿瘤。
我们的研究结果表明，rs10941679-G 等位基因和 rs4415084-T 等位基因可能是乳腺癌发展的风险因素，尤其是在高加索人和东亚人群中。
