Variation in selenoenzyme genes and prostate cancer risk and survival

Authors

  • Milan S. Geybels,

    1. Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
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  • Carolyn M. Hutter,

    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington
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  • Erika M. Kwon,

    1. National Human Genome Research Institute, Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland
    2. Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Elaine A. Ostrander,

    1. National Human Genome Research Institute, Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland
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  • Rong Fu,

    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington
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  • Ziding Feng,

    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington
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  • Janet L. Stanford,

    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington
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  • Ulrike Peters

    Corresponding author
    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington
    • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M4-B874, Seattle, WA 98109-1024.
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Abstract

BACKGROUND

While several studies showed that selenium may prevent prostate cancer (PCa), few studies have evaluated variation in selenoenzyme genes in relation to PCa risk and survival.

METHODS

We studied common variants in seven selenoenzymes genes in relation to risk of PCa and PCa-specific mortality (PCSM). In a population-based case–control study of men of European ancestry (1,309 cases, 1,266 controls), we evaluated 35 common, tagging single nucleotide polymorphisms (SNPs) in GPX1 (n = 2), GPX2 (n = 4), GPX3 (n = 6), GPX4 (n = 6), SEP15 (n = 4), SEPP1 (n = 6), and TXNRD1 (n = 7) in relation to PCa risk, and among cases, associations between these variants and risk of PCSM. We used logistic regression and Cox proportional hazards regression to estimate the relative risk of PCa and PCSM, respectively.

RESULTS

Of the SNPs examined, only GPX1 rs3448 was associated with overall PCa risk with an odds ratio of 0.62 for TT versus CC (95% confidence interval, 0.44–0.88). SNPs in GPX2, GPX3, GPX4, SEP15, and SEPP1 had different risk estimates for PCa in subgroups based on stage and grade. We observed associations between SNPs in GPX4, and TXNRD1 and risk of PCSM. None of these associations, however, remained significant after adjustment for multiple comparisons.

CONCLUSIONS

We found evidence that genetic variation in a subset of selenoenzyme genes may alter risk of PCa and PCSM. These results need validation in additional subsets. Prostate 73: 734–742, 2013. © 2012 Wiley Periodicals, Inc.

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