Cancer Causes & Control

, Volume 24, Issue 1, pp 175–180 | Cite as

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
Original paper

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.

Keywords

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

Notes

Acknowledgments

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.

Supplementary material

10552_2012_103_MOESM1_ESM.doc (312 kb)
Supplementary material 1 (DOC 311 kb)

References

  1. 1.
    Holmes KK, Sparling PF, Stamm WE et al (eds) (2008) Sexually transmitted diseases, 4th edn. McGraw-Hill Medical, New YorkGoogle Scholar
  2. 2.
    Wynder EL, Mabuchi K, Whitmore WF Jr (1971) Epidemiology of cancer of the prostate. Cancer 28(2):344–360PubMedCrossRefGoogle Scholar
  3. 3.
    Gardner WA Jr, Culberson DE, Bennett BD (1986) Trichomonas vaginalis in the prostate gland. Arch Pathol Lab Med 110(5):430–432PubMedGoogle Scholar
  4. 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
  5. 5.
    Sutcliffe S, Giovannucci E, Alderete JF et al (2006) Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 15(5):939–945PubMedCrossRefGoogle Scholar
  6. 6.
    Stark JR, Judson G, Alderete JF et al (2009) Prospective study of Trichomonas vaginalis infection and prostate cancer incidence and mortality: Physicians’ Health Study. J Natl Cancer Inst 101(20):1406–1411PubMedCrossRefGoogle Scholar
  7. 7.
    Sutcliffe S, Alderete JF, Till C et al (2009) Trichomonosis and subsequent risk of prostate cancer in the prostate cancer prevention trial. Int J Cancer 124(9):2082–2087PubMedCrossRefGoogle Scholar
  8. 8.
    Zariffard MR, Harwani S, Novak RM et al (2004) Trichomonas vaginalis infection activates cells through toll-like receptor 4. Clin Immunol 111(1):103–107PubMedCrossRefGoogle Scholar
  9. 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
  10. 10.
    Schroder NW, Schumann RR (2005) Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis 5(3):156–164PubMedGoogle Scholar
  11. 11.
    den Dekker WK, Cheng C, Pasterkamp G, Duckers HJ (2010) Toll like receptor 4 in atherosclerosis and plaque destabilization. Atherosclerosis 209(2):314–320CrossRefGoogle Scholar
  12. 12.
    Chen YC, Giovannucci E, Lazarus R et al (2005) Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer. Cancer Res 65(24):11771–11778PubMedCrossRefGoogle Scholar
  13. 13.
    Wang A, Wang CC, Alderete JF (1987) Trichomonas vaginalis phenotypic variation occurs only among trichomonads infected with the double-stranded RNA virus. J Exp Med 166(1):142–150PubMedCrossRefGoogle Scholar
  14. 14.
    Khoshnan A, Alderete JF (1995) Characterization of double-stranded RNA satellites associated with the Trichomonas vaginalis virus. J Virol 69(11):6892–6897PubMedGoogle Scholar
  15. 15.
    Lehker MW, Alderete JF (1992) Iron regulates growth of Trichomonas vaginalis and the expression of immunogenic trichomonad proteins. Mol Microbiol 6(1):123–132PubMedCrossRefGoogle Scholar
  16. 16.
    Alderete JF (1999) Iron modulates phenotypic variation and phosphorylation of P270 in double-stranded RNA virus-infected Trichomonas vaginalis. Infect Immun 67(8):4298–4302PubMedGoogle Scholar
  17. 17.
    Lehker MW, Arroyo R, Alderete JF (1991) The regulation by iron of the synthesis of adhesins and cytoadherence levels in the protozoan Trichomonas vaginalis. J Exp Med 174(2):311–318PubMedCrossRefGoogle Scholar
  18. 18.
    Alderete JF, Provenzano D, Lehker MW (1995) Iron mediates Trichomonas vaginalis resistance to complement lysis. Microb Pathog 19(2):93–103PubMedCrossRefGoogle Scholar
  19. 19.
    Garcia AF, Benchimol M, Alderete JF (2005) Trichomonas vaginalis polyamine metabolism is linked to host cell adherence and cytotoxicity. Infect Immun 73(5):2602–2610PubMedCrossRefGoogle Scholar
  20. 20.
    Provenzano D, Alderete JF (1995) Analysis of human immunoglobulin-degrading cysteine proteinases of Trichomonas vaginalis. Infect Immun 63(9):3388–3395PubMedGoogle Scholar
  21. 21.
    Lama A, Kucknoor A, Mundodi V, Alderete JF (2009) Glyceraldehyde-3-phosphate dehydrogenase is a surface-associated, fibronectin-binding protein of Trichomonas vaginalis. Infect Immun 77(7):2703–2711PubMedCrossRefGoogle Scholar
  22. 22.
    Alderete JF, Newton E, Dennis C, Neale KA (1991) The vagina of women infected with Trichomonas vaginalis has numerous proteinases and antibody to trichomonad proteinases. Genitourin Med 67(6):469–474PubMedGoogle Scholar
  23. 23.
    Kucknoor AS, Mundodi V, Alderete JF (2007) The proteins secreted by Trichomonas vaginalis and vaginal epithelial cell response to secreted and episomally expressed AP65. Cell Microbiol 9(11):2586–2597PubMedCrossRefGoogle Scholar
  24. 24.
    Kucknoor AS, Mundodi V, Alderete JF (2005) Adherence to human vaginal epithelial cells signals for increased expression of Trichomonas vaginalis genes. Infect Immun 73(10):6472–6478PubMedCrossRefGoogle Scholar
  25. 25.
    Zheng SL, Augustsson-Balter K, Chang B et al (2004) Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the cancer prostate in Sweden study. Cancer Res 64(8):2918–2922PubMedCrossRefGoogle Scholar
  26. 26.
    Cheng I, Plummer SJ, Casey G, Witte JS (2007) Toll-like receptor 4 genetic variation and advanced prostate cancer risk. Cancer Epidemiol Biomarkers Prev 16(2):352–355PubMedCrossRefGoogle Scholar
  27. 27.
    Wang MH, Helzlsouer KJ, Smith MW et al (2009) Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II. Prostate 69(8):874–885PubMedCrossRefGoogle Scholar
  28. 28.
    Stark JR, Wiklund F, Gronberg H et al (2009) Toll-like receptor signaling pathway variants and prostate cancer mortality. Cancer Epidemiol Biomarkers Prev 18(6):1859–1863PubMedCrossRefGoogle Scholar
  29. 29.
    Lindstrom S, Hunter DJ, Gronberg H et al (2010) Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies. Cancer Epidemiol Biomarkers Prev 19(3):873–876PubMedCrossRefGoogle Scholar
  30. 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

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Yen Ching Chen
    • 1
    • 2
    • 3
  • Yi Ling Huang
    • 1
  • Elizabeth A. Platz
    • 4
  • John F. Alderete
    • 5
  • Lu Zheng
    • 6
  • Jennifer R. Rider
    • 7
  • Peter Kraft
    • 6
    • 7
  • Edward Giovannucci
    • 7
    • 8
    • 9
  • Siobhan Sutcliffe
    • 10
  1. 1.Institute of Epidemiology and Preventive Medicine, College of Public HealthNational Taiwan UniversityTaipeiTaiwan
  2. 2.Research Center for Gene, Environment, and Human HealthNational Taiwan UniversityTaipeiTaiwan
  3. 3.Department of Public Health, College of Public HealthNational Taiwan UniversityTaipeiTaiwan
  4. 4.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  5. 5.School of Molecular BiosciencesWashington State UniversityPullmanUSA
  6. 6.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  7. 7.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  8. 8.Channing Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  9. 9.Department of NutritionHarvard School of Public HealthBostonUSA
  10. 10.Division of Public Health Sciences, Department of Surgery, Alvin J. Siteman Cancer CenterWashington University School of MedicineSt. LouisUSA

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