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Genome-wide association study identifies five new breast cancer susceptibility loci


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 × 10−7 to P = 3.2 × 10−15). We also identified SNPs in the 6q25.1 (rs3757318, P = 2.9 × 10−6), 8q24 (rs1562430, P = 5.8 × 10−7) and LSP1 (rs909116, P = 7.3 × 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.

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Figure 1: Manhattan plot of 1-d.f.


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This work was supported by the Wellcome Trust and by Cancer Research UK. D.F.E. is a Principal Research Fellow of Cancer Research UK. C.T. is funded by a Medical Research Council Clinical Research Fellowship. The samples were collected and screened for BRCA mutations through funding from Cancer Research UK; US Military Acquisition (ACQ) Activity, Era of Hope Award (W81XWH-05-1-0204) and the Institute of Cancer Research (UK). This study makes use of data generated by the Wellcome Trust Case Control Consortium (WTCCC) 2. A full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. Funding for this project was provided by the Wellcome Trust under award 085475. We thank the SEARCH team and Eastern Cancer Registry and Information Centre (ECRIC) for recruitment of the SEARCH cases. We acknowledge the clinicians from the Rotterdam Family Cancer Clinic who were involved in collecting the RBCS samples: C. Seynaeve, J. Klijn, J. Collee and R. Oldenburg.

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Authors and Affiliations




D.F.E., N.R., M.R.S., P.D.P.P. and A.M.D. obtained funding for the study. D.F.E. designed the study and drafted the manuscript. D.F.E. and C.T. conducted the statistical analyses. J.M. provided data management and bioinformatics support. C.T. and N.R. coordinated the Familial Breast Cancer Study (FBCS). D.P., A.R., S.S., S.H., D.H., M.W.-P., C.T. and N.R. coordinated the FBCS genotyping. P.D.P.P. and D.F.E. coordinated Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH). S.A., M.M., M.G., C.S.H. and A.M.D. coordinated the stage 2 genotyping of the SEARCH and RBCS samples. M.H., M.S. and A.v.d.O. coordinated and provided samples and data from RBCS. C.L. coordinated the stage 1 genotyping. G.R. and R.H. provided data and samples from the Royal Marsden Hospital (RMH) study. W.T. and D.E. provided data and samples from the Prospective study of Outcomes in Sporadic vs. Hereditary breast cancer (POSH) study. D.E. and D.G.E. provided data and samples for FBCS. All authors provided critical review of the manuscript.

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Correspondence to Douglas F Easton.

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The authors declare no competing financial interests.

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A full list of members is provided in the Supplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1–6, Supplementary Figure 1 and Supplementary Note (PDF 123 kb)

Supplementary Table 3

Genotype counts in cases and controls for all SNPs tested in stages 1 and 2 (XLS 29 kb)

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Turnbull, C., Ahmed, S., Morrison, J. et al. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42, 504–507 (2010).

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