Section of Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey, UK.
Nat Genet. 2010 Jun;42(6):504-7. doi: 10.1038/ng.586. Epub 2010 May 9.
Breast cancer is the most common cancer in women in developed countries. To identify common breast cancer susceptibility alleles, we conducted a genome-wide association study in which 582,886 SNPs were genotyped in 3,659 cases with a family history of the disease and 4,897 controls. Promising associations were evaluated in a second stage, comprising 12,576 cases and 12,223 controls. We identified five new susceptibility loci, on chromosomes 9, 10 and 11 (P = 4.6 x 10(-7) to P = 3.2 x 10(-15)). We also identified SNPs in the 6q25.1 (rs3757318, P = 2.9 x 10(-6)), 8q24 (rs1562430, P = 5.8 x 10(-7)) and LSP1 (rs909116, P = 7.3 x 10(-7)) regions that showed more significant association with risk than those reported previously. Previously identified breast cancer susceptibility loci were also found to show larger effect sizes in this study of familial breast cancer cases than in previous population-based studies, consistent with polygenic susceptibility to the disease.
在发达国家，乳腺癌是女性最常见的癌症。为了鉴定常见的乳腺癌易感等位基因，我们进行了一项全基因组关联研究，对 3659 例有家族病史的病例和 4897 例对照者的 582886 个 SNP 进行了基因分型。在第二阶段，对包含 12576 例病例和 12223 例对照者的样本进行了有前途的关联评估。我们在染色体 9、10 和 11 上鉴定到了五个新的易感位点（P = 4.6 x 10(-7) 至 P = 3.2 x 10(-15)）。我们还在 6q25.1(rs3757318，P = 2.9 x 10(-6))、8q24(rs1562430，P = 5.8 x 10(-7))和 LSP1(rs909116，P = 7.3 x 10(-7))区域鉴定到了与风险相关的 SNP，其关联比以前报道的更为显著。本研究还发现，以前鉴定到的乳腺癌易感位点在家族性乳腺癌病例的研究中比以前基于人群的研究中显示出更大的效应大小，这与疾病的多基因易感性一致。
