Abstract

We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 × 10−12 for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer.

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Acknowledgements

We thank G.H. Olafsdottir for assistance in the ascertainment of individuals with breast cancer. This project was funded in part by contract number 018827 (POLYGENE) from the 6th Framework Programme of the European Union (to S.N.S., T.R. and L.A.K.), the Swedish Cancer Society, the Gustav V Jubilee Foundation, the Bert von Kantzow Foundation and the Nilsson-Ehle Foundation (to A.L. and S.M.) and the US National Cancer Institute (grant CA-RO1 89085-01A to O.I.O).

Author information

Affiliations

  1. deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland.

    • Simon N Stacey
    • , Andrei Manolescu
    • , Patrick Sulem
    • , Steinunn Thorlacius
    • , Sigurjon A Gudjonsson
    • , Gudbjörn F Jonsson
    • , Margret Jakobsdottir
    • , Jon T Bergthorsson
    • , Julius Gudmundsson
    • , Jona Saemundsdottir
    • , Asgeir Sigurdsson
    • , Jelena Kostic
    • , Larus Gudmundsson
    • , Kristleifur Kristjansson
    • , Gisli Masson
    • , Jeffrey R Gulcher
    • , Thorunn Rafnar
    • , Unnur Thorsteinsdottir
    • , Augustine Kong
    •  & Kari Stefansson
  2. Comprehensive Cancer Centre IKO, 6501 BG, Nijmegen, The Netherlands.

    • Katja K Aben
    •  & Lambertus A Kiemeney
  3. Departments of Epidemiology and Biostatistics and Clinical Chemistry and Urology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands.

    • Katja K Aben
    • , Dorine W Swinkels
    •  & Lambertus A Kiemeney
  4. Department of Surgery, Canisius Wilhelmina Hospital, 6500 GS, Nijmegen, The Netherlands.

    • Luc J Strobbe
  5. Department of Surgery, Slingeland Hospital, 7009 BL Doetinchem, The Netherlands.

    • K C Anton van Engelenburg
  6. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

    • Brian E Henderson
    •  & Christopher A Haiman
  7. Cancer Research Center, University of Hawaii, Honolulu, Hawaii 96813, USA.

    • Laurence N Kolonel
    •  & Loic Le Marchand
  8. Division of Medical Oncology, University Hospital, Av. San Juan Bosco 15, 50009 Zaragoza, Spain.

    • Esther Millastre
    • , Raquel Andres
    • , Julio Lambea
    • , Alejandro Tres
    •  & Jose I Mayordomo
  9. Health Science Institute, Nanotechnology Institute of Aragon, 50009 Zaragoza, Spain.

    • Berta Saez
    •  & Javier Godino
  10. Division of Medical Oncology, Ernest Lluch Hospital, 50300 Calatayud, Spain.

    • Eduardo Polo
  11. Department of Molecular Medicine, Karolinska Institutet, S171 76 Stockholm, Sweden.

    • Simone Picelli
    • , Johanna Rantala
    •  & Annika Lindblom
  12. Department of Oncology, Karolinska University Hospital at Södersjukhuset, S118 83 Stockholm, Sweden.

    • Sara Margolin
  13. Departments of Oncology, Surgery, and Radiation Physics, Landspitali-University Hospital, 101 Reykjavik, Iceland.

    • Thorvaldur Jonsson
    • , Helgi Sigurdsson
    • , Thora Jonsdottir
    • , Jon Hrafnkelsson
    • , Jakob Johannsson
    • , Thorarinn Sveinsson
    • , Gardar Myrdal
    • , Hlynur Niels Grimsson
    •  & Oskar T Johannsson
  14. Clinical Research Centre, 110 Reykjavik, Iceland.

    • Steinunn G Sveinsdottir
    •  & Kristin Alexiusdottir
  15. Department of Medicine and Center for Clinical Cancer Genetics, University of Chicago, Chicago, Illinois 60615, USA.

    • James D Fackenthal
    •  & Olufunmilayo I Olopade
  16. Division of Oncology, Department of Surgery, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Oyo State, Nigeria.

    • Clement Adebamowo
    •  & Temidayo Ogundiran

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Contributions

The study was designed by S.N.S., A.M., T. Jonsson, K.K., L.A.K., J.R.G., T.R., U.T., O.T.J., A.K. and K.S. Patient ascertainment, recruitment and medical record review was organized and carried out by S.N.S., S.T., K.K.A., L.J.S., D.W.S., K.C.A.v.E., B.E.H., L.N.K., L.Le.M., E.M., R.A., B.S., J.L., J. Godino, E.P., A.T., S.P., J.R., S.M., H.S., T. Jonsdottir, J.H., J.J., T.S., G. Myrdal, H.N.G., T. Jonsson, L.G., K.K., S.G.S., K.A., J.D.F., C.A., T.O., O.I.O., C.A.H., A.L., J.I.M., L.A.K. and O.T.J. Biological material collection and handling was supervised by S.N.S., K.K., J.I.M., S.G.S, O.I.O., L.A.K., J.S. and U.T. Genotyping was supervised by S.N.S., M.J., A.S., J.K. and U.T. Statistical analysis was carried out by A.M., P.S., G.F.J., J.T.B., J. Gudmundsson and A.K. Bioinformatic analysis was carried out by S.N.S., S.A.G. and G. Masson. S.N.S. and A.M. drafted the manuscript with substantial contributions from P.S., U.T., O.T.J., A.K. and K.S. All authors contributed to the final version of the paper. Principal collaborators for the patient cohorts were O.T.J. (Iceland), L.A.K. (Holland), J.I.M. (Spain), A.L. (Sweden), O.I.O. (Nigeria) and C.A.H. (Multiethnic Cohort, USA).

Competing interests

Authors whose affiliations are listed as deCODE Genetics are shareholders and/or employees of deCODE Genetics, a biotechnology company.

Corresponding authors

Correspondence to Simon N Stacey or Kari Stefansson.

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    Supplementary Methods, Supplementary Figure 1 and Supplementary Tables 1–7

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DOI

https://doi.org/10.1038/ng.131

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