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Evidence for two independent prostate cancer risk–associated loci in the HNF1B gene at 17q12

Nature Genetics volume 40, pages 1153–1155 (2008)Cite this article

Abstract

We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, ∼26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 × 10−9 for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.

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Figure 1: Schematic view of genetic association between SNPs at 17q12 and prostate cancer risk in two study populations.

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Acknowledgements

We thank all the study subjects who participated in this study. We also thank the Regional Cancer Registries and the CAPS-steering committee, including E. Varenhorst. We acknowledge the support of W.T. Gerrard, M. Duhon, Jennifer and John Chalsty and D. Koch. We also thank the National Cancer Institute Cancer Genetic Markers of Susceptibility Initiative (CGEMS) for making the data available publicly. We take full responsibility for the study design, data collection, analysis and interpretation of the data, the decision to submit the manuscript for publication, and the writing of the manuscript. The study is supported by National Cancer Institute (CA106523, CA106523 and CA95052 to J.X., CA112517, CA58236 to W.B.I., CA86323 to A.W.P., Department of Defense grant PC051264 to J.X.), as well as support from Swedish Cancer Society (Cancerfonden) and Swedish Research Council to H.G.

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Author notes

  1. Jielin Sun and Siqun Lilly Zheng: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, 27157, North Carolina, USA

    Jielin Sun, Siqun Lilly Zheng, Lina D Purcell, Zhengrong Gao, Fang-Chi Hsu, Seong-Tae Kim, Wennuan Liu, Yi Zhu, Latchezar Dimitrov, Jishan Sun, Tao Li, Aubrey R Turner, Tamara S Adams, Bao-Li Chang & Jianfeng Xu

  2. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, 27157, North Carolina, USA

    Jielin Sun, Siqun Lilly Zheng, Lina D Purcell, Zhengrong Gao, Seong-Tae Kim, Wennuan Liu, Yi Zhu, Latchezar Dimitrov, Jishan Sun, Tao Li, Aubrey R Turner, Tamara S Adams, Bao-Li Chang & Jianfeng Xu

  3. Department of Medical Epidemiology and Biostatistics, CLINTEC, Karolinska Institute, Stockholm, SE-17177, Sweden

    Fredrik Wiklund, Hans-Olov Adami & Henrik Grönberg

  4. Department of Urology, Johns Hopkins Medical Institutions, Baltimore, 21287, Maryland, USA

    Sarah D Isaacs, Kathleen E Wiley, Bruce J Trock, Alan W Partin, Patrick C Walsh & William B Isaacs

  5. Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, 27157, North Carolina, USA

    Fang-Chi Hsu

  6. Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University Hospital, Umeå, SE-90787, Sweden

    Pär Stattin

  7. Department of Epidemiology, Harvard School of Public Health, Boston, 02115, Massachusetts, USA

    Hans-Olov Adami

  8. Oncological Center, CLINTEC, Karolinska Institutet, Stockholm, SE-17177, Sweden

    Jan Adolfsson

  9. Department of Urology, Örebro University Hospital, Örebro, SE-70182, Sweden

    Jan-Erik Johansson

  10. Translational Genomics Research Institute, Phoenix, 85004, Arizona, USA

    James Lowey, Jeffrey M Trent, David Duggan & John Carpten

Authors
  1. Jielin Sun
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  2. Siqun Lilly Zheng
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  3. Fredrik Wiklund
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  4. Sarah D Isaacs
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  5. Lina D Purcell
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  6. Zhengrong Gao
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  9. Wennuan Liu
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  10. Yi Zhu
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  13. Kathleen E Wiley
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  15. Jishan Sun
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  16. Tao Li
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  17. Aubrey R Turner
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  18. Tamara S Adams
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  19. Jan Adolfsson
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  28. Bao-Li Chang
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  29. Henrik Grönberg
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  30. William B Isaacs
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  31. Jianfeng Xu
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Contributions

J.X., W.B.I., H.G., J.C., D.D. and J.M.T. designed and directed the study. S.L.Z. directed genotyping. Jielin Sun, F.W., F.-C.H., S.-T.K., Y.Z., L.D., Jishan Sun, J.L., B.-L.C. and J.X. conducted data analysis. S.D.I., K.E.W., B.J.T., A.W.P., P.C.W. and W.B.I. were involved in the sample collection at Johns Hopkins Hospital. P.S., H.-O.A., J.A., J.-E.J. and H.G. were involved in the sample collection in Sweden. L.D.P., Z.G., W.L. and T.L. performed laboratory analyses. A.R.T. and T.S.A. provided administrative and technical support for the study.

Corresponding authors

Correspondence to Henrik Grönberg or William B Isaacs.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Tables 1–6, Supplementary Figure 1 (PDF 1008 kb)

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Sun, J., Zheng, S., Wiklund, F. et al. Evidence for two independent prostate cancer risk–associated loci in the HNF1B gene at 17q12. Nat Genet 40, 1153–1155 (2008). https://doi.org/10.1038/ng.214

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