title: Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. karenchen@ntu.edu.tw
authors.forename: Yen Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Yi Ling
authors.initials: YL
authors.lastname: Huang
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: John F
authors.initials: JF
authors.lastname: Alderete
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Rider
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Siobhan
authors.initials: S
authors.lastname: Sutcliffe
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000097:blood / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D004198:Disease Susceptibility / Q000453:epidemiology; D015987:Effect Modifier, Epidemiologic; D060045:Genes, Modifier; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000502:physiology; D014245:Trichomonas Infections / Q000097:blood / Q000150:complications* / Q000453:epidemiology* / Q000276:immunology; D014246:Trichomonas vaginalis / Q000276:immunology / Q000502:physiology
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4