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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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.
KeywordsToll-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.
- 1.Holmes KK, Sparling PF, Stamm WE et al (eds) (2008) Sexually transmitted diseases, 4th edn. McGraw-Hill Medical, New YorkGoogle Scholar
- 4.Smith CJ, Gardner WA Jr (1987) Inflammation-proliferation: possible relationships in the prostate. In: Coffey DS, Bruchovsky N, Gardner WA, Resnick MI, Karr JP (eds) Current concepts and approaches to the study of prostate cancer. Alan R. Liss, Inc., New York, pp 317–25Google Scholar
- 9.Chang JH, Kim SK, Choi IH et al (2006) Apoptosis of macrophages induced by Trichomonas vaginalis through the phosphorylation of p38 mitogen-activated protein kinase that locates at downstream of mitochondria-dependent caspase activation. Int J Biochem Cell Biol 38(4):638–647PubMedCrossRefGoogle Scholar
- 30.Shui IM, Stark JR, Penney KL et al (2012) Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality. Prostate 72(2):209–216Google Scholar