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 journalArticle

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 2013

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Trichomonas vaginalis
Toll-Like Receptor 4
Prostatic Neoplasms
Prospective Studies
Inflammation
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Case-Control Studies
Health
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer. / Chen, Yen Ching; Huang, Yi Ling; Platz, Elizabeth A; Alderete, John F.; Zheng, Lu; Rider, Jennifer R.; Kraft, Peter; Giovannucci, Edward; Sutcliffe, Siobhan.

In: Cancer Causes and Control, Vol. 24, No. 1, 01.2013, p. 175-180.

Research output: Contribution to journalArticle

Chen, Yen Ching ; Huang, Yi Ling ; Platz, Elizabeth A ; Alderete, John F. ; Zheng, Lu ; Rider, Jennifer R. ; Kraft, Peter ; Giovannucci, Edward ; Sutcliffe, Siobhan. / Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer. In: Cancer Causes and Control. 2013 ; Vol. 24, No. 1. pp. 175-180.
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AU - Alderete, John F.

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AU - Rider, Jennifer R.

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AB - 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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