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Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer

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Abstract

Purpose

In previous studies, we observed a positive association between Trichomonas vaginalis serostatus and risk of prostate cancer, particularly aggressive cancer, which we hypothesized might be due to T. vaginalis-mediated intraprostatic inflammation and cell damage. To explore this hypothesis further, we investigated effect modification by Toll-like receptor 4 (TLR4) variation on this association. We hypothesized that TLR4 variation might serve a marker of the anti-trichomonad immune response because T. vaginalis has been shown to elicit inflammation through this receptor.

Methods

We previously genotyped the non-synonymous TLR4 single nucleotide polymorphism (SNP), rs4986790, and determined T. vaginalis serostatus for 690 incident prostate cancer cases and 692 controls in a nested case–control study within the Health Professionals Follow-up Study.

Results

A non-significant suggestion of effect modification was observed by rs4986790 carrier status on the association between T. vaginalis serostatus and prostate cancer risk (p interaction = 0.07). While no association was observed among men homozygous wildtype for this SNP (odds ratio (OR) = 1.23, 95 % confidence interval (CI): 0.86–1.77), a positive association was observed among variant carriers (OR = 4.16, 95 % CI: 1.32–13.1).

Conclusions

Although not statistically significant, TLR4 variation appeared to influence the association between T. vaginalis serostatus and prostate cancer risk consistent with the hypothesis that inflammation plays a role in this association. Larger studies will be necessary to explore this possible effect modification further.

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Acknowledgments

Funding for this study was provided by grants from the US National Cancer Institute (U01 CA98233 and CA55075). Siobhan Sutcliffe was funded by the Barnes-Jewish Hospital Foundation.

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Authors and Affiliations

  1. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

    Yen Ching Chen & Yi Ling Huang

  2. Research Center for Gene, Environment, and Human Health, National Taiwan University, Taipei, Taiwan

    Yen Ching Chen

  3. Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan

    Yen Ching Chen

  4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Elizabeth A. Platz

  5. School of Molecular Biosciences, Washington State University, Pullman, WA, USA

    John F. Alderete

  6. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    Lu Zheng & Peter Kraft

  7. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Jennifer R. Rider, Peter Kraft & Edward Giovannucci

  8. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Edward Giovannucci

  9. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    Edward Giovannucci

  10. Division of Public Health Sciences, Department of Surgery, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Siobhan Sutcliffe

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  1. Yen Ching Chen
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  2. Yi Ling Huang
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  3. Elizabeth A. Platz
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  4. John F. Alderete
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  5. Lu Zheng
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  6. Jennifer R. Rider
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  7. Peter Kraft
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  8. Edward Giovannucci
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  9. Siobhan Sutcliffe
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Corresponding author

Correspondence to Yen Ching Chen.

Additional information

Yen-Ching Chen and Yi-Ling Huang contributed equally to this work.

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Chen, Y.C., Huang, Y.L., Platz, E.A. et al. Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer. Cancer Causes Control 24, 175–180 (2013). https://doi.org/10.1007/s10552-012-0103-y

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  • DOI: https://doi.org/10.1007/s10552-012-0103-y

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