Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality

Authors

  • Irene M. Shui,

    Corresponding author
    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    • Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, 9th Floor, Boston, MA 02115.
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  • Jennifer R. Stark,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
    3. Department of Urology, University of Orebro, Orebro, Sweden
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  • Kathryn L. Penney,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Fredrick R. Schumacher,

    1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • Mara M. Epstein,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Michael J. Pitt,

    1. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Meir J. Stampfer,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
    3. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
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  • Rulla M. Tamimi,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Sara Lindstrom,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • Howard D. Sesso,

    1. Divisions of Preventive Medicine and Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Katja Fall,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
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  • Jing Ma,

    1. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Peter Kraft,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • Edward Giovannucci,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
    3. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
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  • Lorelei A. Mucci

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratory Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
    3. Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland
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  • Conflict of Interest: The authors declare no conflicts of interest.

Abstract

BACKGROUND

Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer.

METHODS

In a large nested case–control study of prostate cancer in the Physicians' Health Study (1982–2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/T4, M1/N1(T1–T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases.

RESULTS

The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases.

CONCLUSIONS

Results from this prospective nested case–control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality. Prostate 72:209–216, 2012. © 2011 Wiley Periodicals, Inc.

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