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RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases

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Abstract

RNASEL (encoding ribonuclease L) has recently been proposed as a candidate for the hereditary prostate cancer (HPC1) gene. We determined that the RNASEL variant Arg462Gln has three times less enzymatic activity than the wildtype and is significantly associated with prostate cancer risk (P = 0.007). At least one copy of the mutated allele that causes this substitution is carried by nearly 60% of the men in our study. Men that are heterozygous with respect to the mutated allele have 50% greater risk of prostate cancer than non-carriers, and homozygotes have more than double the risk.

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Figure 1: Nuclease activity of mutant RNASEL was less than that of wildtype RNASEL.

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Acknowledgements

This work was supported by grants from the US National Institutes of Health, Department of Defense, the Urologic Research Foundation and General Motors Foundation.

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Authors and Affiliations

  1. Department of Cancer Biology, ND50, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, 44195, Ohio, USA

    Graham Casey, Phillippa J. Neville, Sarah J. Plummer, Ying Xiang, Lisa M. Krumroy & Robert H. Silverman

  2. Urology Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, 44195, Ohio, USA

    Eric A. Klein

  3. Department of Urologic Surgery, Washington University, St. Louis, Missouri, USA

    William J. Catalona

  4. Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA

    Nina Nupponen, John D. Carpten & Jeffrey M. Trent

  5. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA

    John S. Witte

Authors
  1. Graham Casey
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  2. Phillippa J. Neville
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  3. Sarah J. Plummer
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  4. Ying Xiang
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  5. Lisa M. Krumroy
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  6. Eric A. Klein
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  7. William J. Catalona
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  8. Nina Nupponen
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  9. John D. Carpten
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  10. Jeffrey M. Trent
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  11. Robert H. Silverman
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  12. John S. Witte
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Corresponding authors

Correspondence to Graham Casey or John S. Witte.

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The authors declare no competing financial interests.

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Casey, G., Neville, P., Plummer, S. et al. RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. Nat Genet 32, 581–583 (2002). https://doi.org/10.1038/ng1021

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  • DOI: https://doi.org/10.1038/ng1021

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