Cancer Causes & Control

, Volume 24, Issue 1, pp 175–180 | Cite as

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

  • Yen Ching Chen
  • Yi Ling Huang
  • Elizabeth A. Platz
  • John F. Alderete
  • Lu Zheng
  • Jennifer R. Rider
  • Peter Kraft
  • Edward Giovannucci
  • Siobhan Sutcliffe
Original paper



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.


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.


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).


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.


Toll-like receptor 4 T. vaginalis Prostate cancer SNP Aspirin 



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.

Supplementary material

10552_2012_103_MOESM1_ESM.doc (312 kb)
Supplementary material 1 (DOC 311 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Yen Ching Chen
    • 1
    • 2
    • 3
  • Yi Ling Huang
    • 1
  • Elizabeth A. Platz
    • 4
  • John F. Alderete
    • 5
  • Lu Zheng
    • 6
  • Jennifer R. Rider
    • 7
  • Peter Kraft
    • 6
    • 7
  • Edward Giovannucci
    • 7
    • 8
    • 9
  • Siobhan Sutcliffe
    • 10
  1. 1.Institute of Epidemiology and Preventive Medicine, College of Public HealthNational Taiwan UniversityTaipeiTaiwan
  2. 2.Research Center for Gene, Environment, and Human HealthNational Taiwan UniversityTaipeiTaiwan
  3. 3.Department of Public Health, College of Public HealthNational Taiwan UniversityTaipeiTaiwan
  4. 4.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  5. 5.School of Molecular BiosciencesWashington State UniversityPullmanUSA
  6. 6.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  7. 7.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  8. 8.Channing Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  9. 9.Department of NutritionHarvard School of Public HealthBostonUSA
  10. 10.Division of Public Health Sciences, Department of Surgery, Alvin J. Siteman Cancer CenterWashington University School of MedicineSt. LouisUSA

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