Estimation of absolute risk for prostate cancer using genetic markers and family history

Authors

  • Jianfeng Xu,

    Corresponding author
    1. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    2. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    • Center for Cancer Genomics, Medical Center Blvd, Winston-Salem, NC 27157.
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  • Jielin Sun,

    1. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    2. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • A. Karim Kader,

    1. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    2. Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • Sara Lindström,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • Fredrik Wiklund,

    1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • Fang-Chi Hsu,

    1. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    2. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    3. Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • Jan-Erik Johansson,

    1. Department of Urology, Örebro University Hospital, Örebro, Sweden
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  • S. Lilly Zheng,

    1. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    2. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • Gilles Thomas,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Maryland
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  • Richard B. Hayes,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Maryland
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  • Peter Kraft,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Maryland
    2. Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • David J. Hunter,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Maryland
    2. Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • Stephen J. Chanock,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Maryland
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  • William B. Isaacs,

    Corresponding author
    1. The Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland
    • Marburg 115, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21287.
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  • Henrik Grönberg

    1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • There is no potential conflict of interest relevant to this article.

Abstract

BACKGROUND

Multiple DNA sequence variants in the form of single-nucleotide polymorphisms (SNPs) have been found to be reproducibly associated with prostate cancer (PCa) risk.

METHODS

Absolute risk for PCa among men with various numbers of inherited risk alleles and family history of PCa was estimated in a population-based case–control study in Sweden (2,893 cases and 1,781 controls), and a nested case–control study from the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening Trial in the U.S. (1,172 cases and 1,157 controls).

RESULTS

Increased number of risk alleles and positive family history were independently associated with PCa risk. Considering men with 11 risk alleles (mode) and negative family history as having baseline risk, men who had ≥14 risk alleles and positive family history had an odds ratio (OR) of 4.92 [95% confidence interval (CI): 3.64–6.64] in the Swedish study. These associations were confirmed in the U.S. population. Once a man's SNP genotypes and family history are known, his absolute risk for PCa can be readily calculated and easily interpreted. For example, 55-year-old men with a family history and ≥14 risk alleles have a 52% and 41% risk of being diagnosed with PCa in the next 20 years in the Swedish and U.S. populations, respectively. In comparison, without knowledge of genotype and family history, these men had an average population absolute risk of 13%.

CONCLUSION

This risk prediction model may be used to identify men at considerably elevated PCa risk who may be selected for chemoprevention. Prostate 69: 1565–1572, 2009. © 2009 Wiley-Liss, Inc.

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