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.
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.
Authors: Irene M Shui; Jennifer R Stark; Kathryn L Penney; Fredrick R Schumacher; Mara M Epstein; Michael J Pitt; Meir J Stampfer; Rulla M Tamimi; Sara Lindstrom; Howard D Sesso; Katja Fall; Jing Ma; Peter Kraft; Edward Giovannucci; Lorelei A Mucci Journal: Prostate Date: 2011-05-11 Impact factor: 4.104
Authors: Sara Lindström; David J Hunter; Henrik Grönberg; Pär Stattin; Fredrik Wiklund; Jianfeng Xu; Stephen J Chanock; Richard Hayes; Peter Kraft Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-03-03 Impact factor: 4.254
Authors: S Lilly Zheng; Katarina Augustsson-Bälter; Baoli Chang; Maria Hedelin; Liwu Li; Hans-Olov Adami; Jeanette Bensen; Ge Li; Jan-Erik Johnasson; Aubrey R Turner; Tamara S Adams; Deborah A Meyers; William B Isaacs; Jianfeng Xu; Henrik Grönberg Journal: Cancer Res Date: 2004-04-15 Impact factor: 12.701
Authors: Jennifer R Stark; Gregory Judson; John F Alderete; Vasanthakrishna Mundodi; Ashwini S Kucknoor; Edward L Giovannucci; Elizabeth A Platz; Siobhan Sutcliffe; Katja Fall; Tobias Kurth; Jing Ma; Meir J Stampfer; Lorelei A Mucci Journal: J Natl Cancer Inst Date: 2009-09-09 Impact factor: 13.506