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Two-locus genome-wide linkage scan for prostate cancer susceptibility genes with an interaction effect

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Abstract

Prostate cancer represents a significant worldwide public health burden. Epidemiological and genetic epidemiological studies have consistently provided data supporting the existence of inherited prostate cancer susceptibility genes. Segregation analyses of prostate cancer suggest that a multigene model may best explain familial clustering of this disease. Therefore, modeling gene–gene interactions in linkage analysis may improve the power to detect chromosomal regions harboring these disease susceptibility genes. In this study, we systematically screened for prostate cancer linkage by modeling two-locus gene–gene interactions for all possible pairs of loci across the genome in 426 prostate cancer families from Johns Hopkins Hospital, University of Michigan, University of Umeå, and University of Tampere. We found suggestive evidence for an epistatic interaction for six sets of loci (target chromosome-wide/reference marker-specific P≤0.0001). Evidence for these interactions was found in two independent subsets from within the 426 families. While the validity of these results requires confirmation from independent studies and the identification of the specific genes underlying this linkage evidence, our approach of systematically assessing gene–gene interactions across the entire genome represents a promising alternative approach for gene identification for prostate cancer.

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Authors and Affiliations

  1. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Bao-Li Chang, Latchezar Dimitrov, S. Lilly Zheng & Jianfeng Xu

  2. Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Christopher J. Valis, Carl D Langefeld & Jianfeng Xu

  3. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    Ethan M. Lange & Leslie A. Lange

  4. Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA

    Ethan M. Lange

  5. National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA

    Elizabeth M. Gillanders & Joan E. Bailey-Wilson

  6. Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Kathleen E. Wiley, Sarah D. Isaacs, Patrick C. Walsh & William B. Isaacs

  7. Department of Internal Medicine and Urology, University of Michigan, Ann Arbor, MI, USA

    Kathleen A. Cooney

  8. Department of Radiation Sciences, Oncology, University of Umeå, Umeå, Sweden

    Fredrik Wiklund & Henrik Gronberg

  9. Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA, USA

    Agnes Baffoe-Bonnie

  10. Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland

    Mika P. Matikainen & Teuvo Tammela

  11. Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland

    Mika P. Matikainen, Tarja Ikonen, Henna Fredriksson & Johanna Schleutker

  12. Translational Genomics Research Institute (TGen), Phoenix, AZ, USA

    Edward Suh, Jeffrey M. Trent & Jianfeng Xu

  13. Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Jianfeng Xu

Authors
  1. Bao-Li Chang
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  2. Ethan M. Lange
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  3. Latchezar Dimitrov
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  4. Christopher J. Valis
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  5. Elizabeth M. Gillanders
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  6. Leslie A. Lange
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  7. Kathleen E. Wiley
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  8. Sarah D. Isaacs
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  9. Fredrik Wiklund
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  10. Agnes Baffoe-Bonnie
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  11. Carl D Langefeld
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  12. S. Lilly Zheng
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  13. Mika P. Matikainen
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  14. Tarja Ikonen
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  15. Henna Fredriksson
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  16. Teuvo Tammela
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  17. Patrick C. Walsh
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  18. Joan E. Bailey-Wilson
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  19. Johanna Schleutker
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  20. Henrik Gronberg
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  21. Kathleen A. Cooney
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  22. William B. Isaacs
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  23. Edward Suh
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  24. Jeffrey M. Trent
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  25. Jianfeng Xu
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Corresponding author

Correspondence to Jianfeng Xu.

Additional information

Bao-Li Chang and Ethan M. Lange have contributed equally to the work

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Chang, BL., Lange, E.M., Dimitrov, L. et al. Two-locus genome-wide linkage scan for prostate cancer susceptibility genes with an interaction effect. Hum Genet 118, 716–724 (2006). https://doi.org/10.1007/s00439-005-0099-4

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  • DOI: https://doi.org/10.1007/s00439-005-0099-4

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