Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Cancer Epidemiol Biomarkers Prev. 2013 Jul;22(7):1297-303. doi: 10.1158/1055-9965.EPI-12-1393. Epub 2013 May 15.
Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study (GWAS) conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations.
We evaluated nine of those nonreplication loci in East Asians to identify new risk variants for breast cancer in these regions. First, we analyzed single-nucleotide polymorphisms (SNP) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (stage 1). In each region, we selected an SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (stage 2). Logistic regression models were used to calculate adjusted ORs and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants.
Two SNPs were replicated in stage 2 at P < 0.05: rs1419026 at 6q14 [per allele OR, 1.07; 95% confidence interval (CI), 1.03-1.12; P = 3.0 × 10(-4)] and rs941827 at 10q25 (OR, 0.92, 95% CI, 0.89-0.96; P = 5.3 × 10(-5)). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR, 0.88; 95% CI, 0.82-0.97; P = 5.3 × 10(-5)).
We identified a new breast cancer risk variant at 10q25 in East Asian women.
Results from this study improve the understanding of the genetic basis for breast cancer.
最近，在一项针对欧洲后裔的全基因组关联研究（GWAS）中，发现了 41 个新的乳腺癌风险遗传易感性位点。这些风险变异体中的大多数尚未在亚洲人群中得到直接复制。
我们评估了东亚人群中这 9 个非复制位点，以确定这些地区乳腺癌的新风险变异体。首先，我们使用中国和韩国女性进行的两项 GWAS 中的数据分析了这些区域的单核苷酸多态性（SNP），包括 5083 例病例和 4376 例对照（阶段 1）。在每个区域中，我们选择与乳腺癌风险关联最强的 SNP 用于对东亚血统的 7294 例病例和 9404 例对照进行独立复制（阶段 2）。使用逻辑回归模型计算调整后的 OR 和 95%置信区间（CI）作为乳腺癌风险和遗传变异体关联的度量。
在阶段 2 中，有两个 SNP 达到了 P < 0.05 的复制水平：位于 6q14 的 rs1419026[每个等位基因的 OR，1.07；95%置信区间（CI），1.03-1.12；P = 3.0×10(-4)]和位于 10q25 的 rs941827（OR，0.92，95%CI，0.89-0.96；P = 5.3×10(-5)）。在调整了最初在欧洲裔女性中发现的风险变异体后，rs941827 的相关性仍然具有统计学意义（OR，0.88；95%CI，0.82-0.97；P = 5.3×10(-5)）。
我们在东亚女性中发现了 10q25 上的一个新的乳腺癌风险变异体。
本研究的结果提高了对乳腺癌遗传基础的认识。
