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Common variants in ZNF365 are associated with both mammographic density and breast cancer risk


High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10−10). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer.

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Figure 1: Regional association plot for ZNF365 across a 300-kb window.

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This study was supported by Public Health Service Grants CA131332, CA087969, CA049449, CA128931, CA116201, CA075016, CA122340 and CA089393 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services and Breast Cancer Research Fund. The Nurses' Health Study (NHS) breast cancer cases and controls were genotyped with support from the National Cancer Institute's Cancer Markers of Susceptibility (CGEMS) initiative. Data evaluation of mammograms and analysis of the EPIC-Norfolk and SIBS studies was supported by Cancer Research UK. The SASBAC study was supported by Märit and Hans Rausing's Initiative against Breast Cancer, National Institutes of Health, Susan Komen Foundation and Agency for Science, Technology and Research of Singapore (A*STAR). Genotyping in the TORONTO/MELBOURNE subjects was supported by the Campbell Family Institute for Breast Cancer Research. Support was also provided by the Ontario Ministry of Health and Long Term Care.

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S.L., C.M.V., J.L.H., P.K., P.H., D.F.E., N.F.B. and R.M.T. designed and executed the study. S.L., J. Li, J.V., A.D.P., D.W., C.G.S., V.S.P., J.S., K.C. and P.K. led the statistical analysis. C.M.V., D.T., R.W., J.B., J. Leyland, T.A., N.J.W., R.J.F.L., A.D.P., L.J.M., S.E.H., A.H., D.J.H., J.L.H., M.C.S., S.J.C., I.d.S.S., J. Liu, L.E., F.J.C., C.A., K.C., P.H., D.F.E., N.F.B. and R.M.T. collected and provided data to the initial GWAS analysis and replication studies. S.L., C.M.V., J. Li, D.T., R.J.F.L., J.L.H., J.S., D.F.E. and R.M.T. wrote the manuscript with contributions from all the authors.

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Correspondence to Rulla M Tamimi.

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The authors declare no competing financial interests.

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Supplementary Figures 1 and 2, Supplementary Tables 1–6 and Supplementary Methods (PDF 369 kb)

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Lindström, S., Vachon, C., Li, J. et al. Common variants in ZNF365 are associated with both mammographic density and breast cancer risk. Nat Genet 43, 185–187 (2011).

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