A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer (original) (raw)

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Acknowledgements

We thank B. Egan, L. Egan, H. Judge Ellis, H. Ranu and P. Soule for assistance, and we thank the participants in the Nurses' Health Studies. We thank P. Prorok (Division of Cancer Prevention, National Cancer Institute); the Screening Center investigators and staff of PLCO; T. Riley, C. Williams and staff (Information Management Services, Inc.); B. O'Brien and staff (Westat, Inc.) and B. Kopp, T. Sheehy and staff (SAIC-Frederick). We acknowledge the study participants for their contributions in making this study possible. We thank C. Lichtman for data management and the participants on the CPS-II. We thank M. Minichiello for providing the Margarita program and for discussions. We acknowledge D. Easton and colleagues for sharing prepublication results. The Nurses' Health Studies are supported by US NIH grants CA65725, CA87969, CA49449, CA67262, CA50385 and 5UO1CA098233. The ACS study is supported by UO1 CA098710. The PLCO study is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS.

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Authors and Affiliations

  1. Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, 02115, Massachusetts, USA
    David J Hunter, David G Cox, Susan E Hankinson & Walter C Willett
  2. Department of Epidemiology, Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
    David J Hunter, Peter Kraft & David G Cox
  3. Broad Institute of Harvard and MIT, Cambridge, 02142, Massachusetts, USA
    David J Hunter
  4. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services (DHHS), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, 20892, Maryland, USA
    David J Hunter, Meredith Yeager, Sholom Wacholder, Zhaoming Wang, Robert Welch, Amy Hutchinson, Junwen Wang, Kai Yu, Nilanjan Chatterjee, Regina G Ziegler, Richard B Hayes, Margaret Tucker, Joseph F Fraumeni Jr, Robert N Hoover, Gilles Thomas & Stephen J Chanock
  5. Bioinformed Consulting Services, Gaithersburg, 20877, Maryland, USA
    Kevin B Jacobs
  6. SAIC-Frederick, NCI-FCRDC, Frederick, 21702, Maryland, USA
    Meredith Yeager, Zhaoming Wang, Robert Welch, Amy Hutchinson & Junwen Wang
  7. Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, DHHS, Bethesda, 20892, Maryland, USA
    Nick Orr & Stephen J Chanock
  8. Department of Nutrition, Harvard School of Public Health, Boston, 02115, Massachusetts, USA
    Walter C Willett
  9. Washington University School of Medicine, St. Louis, 63130, Missouri, USA
    Graham A Colditz
  10. Division of Cancer Prevention, NCI, NIH, DHHS, Bethesda, 20892, Maryland, USA
    Christine D Berg
  11. Department of Internal Medicine, University of Utah, Salt Lake City, 84112, Utah, USA
    Saundra S Buys
  12. The Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, 54449, Wisconsin, USA
    Catherine A McCarty
  13. Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, 30329, Georgia, USA
    Heather Spencer Feigelson, Eugenia E Calle & Michael J Thun
  14. Office of Cancer Genomics, NCI, NIH, DHHS, Bethesda, 20892, Maryland, USA
    Daniela S Gerhard

Authors

  1. David J Hunter
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  2. Peter Kraft
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  3. Kevin B Jacobs
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  4. David G Cox
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  5. Meredith Yeager
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  6. Susan E Hankinson
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  7. Sholom Wacholder
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  8. Zhaoming Wang
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  9. Robert Welch
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  10. Amy Hutchinson
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  11. Junwen Wang
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  12. Kai Yu
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  13. Nilanjan Chatterjee
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  14. Nick Orr
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  15. Walter C Willett
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  16. Graham A Colditz
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  17. Regina G Ziegler
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  18. Christine D Berg
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  19. Saundra S Buys
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  20. Catherine A McCarty
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  21. Heather Spencer Feigelson
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  22. Eugenia E Calle
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  23. Michael J Thun
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  24. Richard B Hayes
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  25. Margaret Tucker
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  26. Daniela S Gerhard
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  27. Joseph F Fraumeni Jr
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  28. Robert N Hoover
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  29. Gilles Thomas
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  30. Stephen J Chanock
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Corresponding author

Correspondence toDavid J Hunter.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Distribution of the admixture vector of each NHS participant as determined by STRUCTURE. (PDF 41 kb)

Supplementary Fig. 2

Probability-probability plot of the uncorrected P values (blue dots) compared with the expected uniform distribution (green line), where magenta dots show the P values corrected for age in 5-year intervals, an indicator for recent hormone use, and three eigenvectors controlling for population stratification. (PDF 77 kb)

Supplementary Fig. 3

ARG analysis with 81 SNPs after 106 permutations. (PDF 55 kb)

Supplementary Table 1

Identification of protective and at-risk haplotypes for the FGFR2 susceptibility locus. (PDF 79 kb)

Supplementary Table 2

Evidence for association between the six most significant SNPs in the NHS genome-wide association scan, the three replication studies, and the pooled scan and replication data. (PDF 56 kb)

Supplementary Methods (PDF 20 kb)

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Hunter, D., Kraft, P., Jacobs, K. et al. A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer.Nat Genet 39, 870–874 (2007). https://doi.org/10.1038/ng2075

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