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

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Pages (from-to)175-180
Number of pages6
JournalCancer Causes and Control
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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