Association of variants in estrogen-related pathway genes with prostate cancer risk

Authors

  • Sarah K. Holt,

    Corresponding author
    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • Fred Hutchinson Cancer Research Center, Mailstop: M4-A402, P.O. Box 19024, Seattle, WA 98109.
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  • Erika M. Kwon,

    1. Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland
    2. Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Rong Fu,

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

    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 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, University of Washington, Seattle, Washington
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  • Elaine A. Ostrander,

    1. Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland
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  • Janet L. Stanford

    1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Epidemiology, University of Washington, Seattle, Washington
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  • There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Abstract

BACKGROUND

Through mediation of estrogen receptors, estradiol has been shown to have both carcinogenic and anti-carcinogenic effects on the prostate. We performed a population-based case–control study to investigate variants in estrogen-related genes ESR1, ESR2, CYP19A1, CYP1A1, and CYP1B1 and the potential association with risk of prostate cancer (PCa).

MATERIALS AND METHODS

We evaluated PCa risk conferred by 73 single nucleotide polymorphisms in 1,304 incident PCa cases and 1,266 age-matched controls. Analysis included stratification by clinical features and assessment of environmental modifiers.

RESULTS

There was evidence of altered risk of developing PCa for variants in ESR1, CYP1A1, and CYP1B1, however, only CYP1B1 rs1056836 retained significance after adjustment for multiple comparisons. An association with risk for more aggressive PCa was observed for variants in ESR1, ESR2, and CYP19A1, but none was significant after adjustment for multiple comparisons. There was no effect modification by obesity.

CONCLUSIONS

Germline genetic variation of these estrogen pathway genes may contribute to risk of PCa. Additional studies to validate these results and examine the functional consequence of validated variants are warranted. Prostate 73: 1–10, 2013. © 2012 Wiley Periodicals, Inc.

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