Genetic variants of 6q25 and breast cancer susceptibility: a two-stage fine mapping study in a Chinese population
Genetic variants of 6q25 and breast cancer susceptibility: a two-stage fine mapping study in a Chinese population
复制标题
DOI：
10.1007/s10549-011-1527-x
复制
发表时间：
2011-10-01
影响因子：
3.8
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
--
作者：
Han, Jing;Jiang, Tao;Shen, Hongbing
最近的一项全基因组关联研究发现，6q25区域的一种新的单核苷酸多态性（SNP） rs2046210是中国人乳腺癌的易感性位点，随后在一项多中心研究中得到了证实。对该区域的进一步精细定位可能有助于确定乳腺癌的潜在致病snp。我们采用基于块的精细定位分析，研究了6q25区域标记snp rs2046210在41 kb块中的标记snp，并通过两阶段病例对照研究扩展了我们的研究，在ESR1基因中纳入了两个潜在的功能snp (rs2234693和rs1801132)，其中1,792例乳腺癌病例和1,867例对照（测试组878例和900例对照，验证组914例和967例对照）。在控制多重检测后，检测集中6q25区域41 kb片段的rs1038304、rs6929137、rs2046210和rs10484919与乳腺癌风险存在显著相关性。与验证集样本一起，这四个snp都与乳腺癌风险增加显著相关（加性OR从1.25到1.34，加性P从4.84 × 10（-6）到7.17 × 10(-9)）。经过条件回归和连锁不平衡分析，发现rs6929137和rs10484919是该区域乳腺癌的易感标记，根据UCSC （http://genome.ucsc.edu/）基因组数据库，它们都位于组蛋白修饰位点。我们的研究结果支持6q25区域是中国女性乳腺癌的重要易感区域，rs6929137和rs10484919是该区域的致病snp或标记snp。
A recent genome-wide association study identified a novel single nucleotide polymorphism (SNP), rs2046210, in the 6q25 region as a breast cancer susceptibility locus in Chinese and subsequently replicated in a multicenter study. Further fine-mapping of this region may help identify the potential causative SNPs of breast cancer. We employed a block-based fine mapping analysis to investigate the tagging SNPs in a 41 kb block with the marker-SNP rs2046210 in the 6q25 region, and also extended our study by including two potentially functional SNPs (rs2234693 and rs1801132) within the ESR1 gene by a two-stage case-control study with 1,792 breast cancer cases and 1,867 controls (878 cases and 900 controls in the testing set and 914 cases and 967 controls in the validation set). Significant associations with breast cancer risk were observed for rs1038304, rs6929137, rs2046210, and rs10484919 in the 41 kb block of the 6q25 region in the testing set after controlling multiple testing. Together with the validation set samples, these four SNPs were all significantly associated with increased risk of breast cancer (additive OR from 1.25 to 1.34, additive P from 4.84 x 10(-6) to 7.17 x 10(-9)). After conditional regression and linkage disequilibrium analyses, rs6929137 and rs10484919 tend to be susceptible markers of breast cancer in this region and both of them were located at sites of histone modification according to the UCSC (http://genome.ucsc.edu/) genome database. Our results support that the 6q25 region is an important susceptibility region for breast cancer in Chinese women, and rs6929137 and rs10484919 are causative or marker SNPs for this region.