Original paper

Cancer Causes & Control

, Volume 24, Issue 1, pp 175-180

First online:

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

  • Yen Ching ChenAffiliated withInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan UniversityResearch Center for Gene, Environment, and Human Health, National Taiwan UniversityDepartment of Public Health, College of Public Health, National Taiwan University Email author 
  • , Yi Ling HuangAffiliated withInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University
  • , Elizabeth A. PlatzAffiliated withDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health
  • , John F. AldereteAffiliated withSchool of Molecular Biosciences, Washington State University
  • , Lu ZhengAffiliated withDepartment of Biostatistics, Harvard School of Public Health
  • , Jennifer R. RiderAffiliated withDepartment of Epidemiology, Harvard School of Public Health
  • , Peter KraftAffiliated withDepartment of Biostatistics, Harvard School of Public HealthDepartment of Epidemiology, Harvard School of Public Health
  • , Edward GiovannucciAffiliated withDepartment of Epidemiology, Harvard School of Public HealthChanning Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Nutrition, Harvard School of Public Health
  • , Siobhan SutcliffeAffiliated withDivision of Public Health Sciences, Department of Surgery, Alvin J. Siteman Cancer Center, Washington University School of Medicine

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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.

Keywords

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