Zheng Wei, Long Jirong, Gao Yu-Tang, Li Chun, Zheng Ying, Xiang Yong-Bin, Wen Wanqing, Levy Shawn, Deming Sandra L, Haines Jonathan L, Gu Kai, Fair Alecia Malin, Cai Qiuyin, Lu Wei, Shu Xiao-Ou
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Nat Genet. 2009 Mar;41(3):324-8. doi: 10.1038/ng.318. Epub 2009 Feb 15.
We carried out a genome-wide association study among Chinese women to identify risk variants for breast cancer. After analyzing 607,728 SNPs in 1,505 cases and 1,522 controls, we selected 29 SNPs for a fast-track replication in an independent set of 1,554 cases and 1,576 controls. We further investigated four replicated loci in a third set of samples comprising 3,472 cases and 900 controls. SNP rs2046210 at 6q25.1, located upstream of the gene encoding estrogen receptor alpha (ESR1), showed strong and consistent association with breast cancer across all three stages. Adjusted odds ratio (95% CI) were 1.36 (1.24-1.49) and 1.59 (1.40-1.82), respectively, for genotypes A/G and A/A versus G/G (P for trend 2.0 x 10(-15)) in the pooled analysis of samples from all three stages. We also found a similar, albeit weaker, association in an independent study comprising 1,591 cases and 1,466 controls of European ancestry (P(trend) = 0.01). These results strongly implicate 6q25.1 as a susceptibility locus for breast cancer.
我们在中国女性中开展了一项全基因组关联研究，以确定乳腺癌的风险变异。在分析了1505例病例和1522例对照中的607,728个单核苷酸多态性（SNP）后，我们选择了29个SNP在另一组独立的1554例病例和1576例对照中进行快速验证。我们在包含3472例病例和900例对照的第三组样本中进一步研究了4个验证位点。位于雌激素受体α（ESR1）编码基因上游的6q25.1处的SNP rs2046210在所有三个阶段均显示出与乳腺癌有强烈且一致的关联。在对所有三个阶段的样本进行汇总分析时，基因型A/G和A/A与G/G相比，调整后的优势比（95%可信区间）分别为1.36（1.24 - 1.49）和1.59（1.40 - 1.82）（趋势P值为2.0×10⁻¹⁵）。在一项包含1591例欧洲血统病例和1466例对照的独立研究中，我们也发现了类似的关联，尽管较弱（趋势P值 = 0.01）。这些结果有力地表明6q25.1是乳腺癌的一个易感位点。
