Molecular Biology Reports

, Volume 39, Issue 7, pp 7263–7269

Association of Toll-like receptor (TLR) 2, 3 and 9 genes polymorphism with prostate cancer risk in North Indian population

  • Raju K. Mandal
  • Ginu P. George
  • Rama D. Mittal
Article

Abstract

Prostate cancer (PCa) is the most common cancer among men. It has been suggested that toll like receptors (TLRs) may contribute to PCa pathogenesis by stimulating prostate epithelial cell proliferation in response to infectious stimuli. We performed case control study to analyze the genetic variants of TLR2, 3 and 9 gene polymorphisms with PCa risk in a North Indian population. For this study we genotyped age matched, unrelated 195 PCa patients and 250 healthy controls of similar ethnicity in a case–control study. They were genotyped for TLR2 (−196 to −174 Del), TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] gene polymorphisms using polymerase chain reaction and restriction fragment length polymorphism method. Variant allele Del (D) carriers i.e. (ID + DD) of TLR2 (−196 to −174 Del) SNP, demonstrated 1.57 fold increased risk (p = 0.040; OR = 1.57, 95% CI = 1.02–2.24) as compared to Ins (I) allele, suggesting a dominant effect model involved in the risk of this polymorphism in PCa. However, variants of TLR3 and 9 gene polymorphisms were not associated with PCa risk. Our results suggested the low penetrance variant of TLR2 (−196 to −174 Del) to be at increased PCa risk in North Indian population. Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for PCa etiology.

Keywords

Toll-like receptors Polymorphism Prostate cancer 

References

  1. 1.
    Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 5:277–300CrossRefGoogle Scholar
  2. 2.
    Sinha R, Anderson DE, McDonald SS, Greenwald P (2003) Cancer risk and diet in India. J Postgrad Med 49:222–228PubMedGoogle Scholar
  3. 3.
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M et al (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85PubMedCrossRefGoogle Scholar
  4. 4.
    Tanner MA, Shoskes D, Shahed A, Pace NR (1999) Prevalence of corynebacterial 16S rRNA sequences in patients with bacterial and “nonbacterial” prostatitis. J Clin Microbiol 37:1863–1870PubMedGoogle Scholar
  5. 5.
    Boldogh I, Baskar JF, Mar EC, Huang ES (1983) Human cytomegalovirus and herpes simplex type 2 virus in normal and adenocarcinomatous prostate glands. J Natl Cancer Inst 70:819–826PubMedGoogle Scholar
  6. 6.
    Serth J, Panitz F, Paeslack U, Kuczyk MA, Jonas U (1999) Increased levels of human papillomavirus type 16 DNA in a subset of prostate cancers. Cancer Res 59:823–825PubMedGoogle Scholar
  7. 7.
    Aderem A, Ulevitch RJ (2000) Toll-like receptors in the induction of the innate immune response. Nature 406:782–787PubMedCrossRefGoogle Scholar
  8. 8.
    Cheng I, Plummer SJ, Casey G, Witte JS (2007) Toll-like receptor 4 genetic variation and advanced prostate cancer risk. Cancer Epidemiol Biomarkers Prev 16:352–355PubMedCrossRefGoogle Scholar
  9. 9.
    Chen YC, Giovannucci E, Lazarus R, Kraft P, Ketkar S, Hunter DJ (2005) Sequence variants of toll-like receptor 4 and susceptibility to prostate cancer. Cancer Res 65:11771–11778PubMedCrossRefGoogle Scholar
  10. 10.
    Kundu SD, Lee C, Billips BK, Habermacher GM, Zhang Q, Liu V et al (2008) The toll-like receptor pathway: a novel mechanism of infection-induced carcinogenesis of prostate epithelial cells. Prostate 68:223–229PubMedCrossRefGoogle Scholar
  11. 11.
    Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145PubMedCrossRefGoogle Scholar
  12. 12.
    Pandey S, Agrawal DK (2006) Immunobiology of toll-like receptors: emerging trends. Immunol Cell Biol 84:333–341PubMedCrossRefGoogle Scholar
  13. 13.
    El Omar EM, Ng MT, Hold GI (2008) Polymorphisms in toll like receptor genes and risk of Cancer. Oncogene 27:244–252PubMedCrossRefGoogle Scholar
  14. 14.
    Schroder NW, Schumann RR (2005) Single nucleotide polymorphisms of toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis 5:156–164PubMedGoogle Scholar
  15. 15.
    Gleason DF, Mellinger GT (1974) Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111:58–64PubMedGoogle Scholar
  16. 16.
    Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedCrossRefGoogle Scholar
  17. 17.
    Tahara T, Arisawa T, Wang F, Shibata T, Nakamura M, Sakata M et al (2007) Toll-like receptor 2—196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer. Cancer Sci 98:1790–17904PubMedCrossRefGoogle Scholar
  18. 18.
    Pandey S, Mittal B, Srivastava M, Singh S, Srivastava K, Lal P et al (2010) Evaluation of toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in cervical cancer susceptibility. Mol Biol Rep 38:4715–4721PubMedCrossRefGoogle Scholar
  19. 19.
    Le Bon A, Tough DF (2002) Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol 14:432–436PubMedCrossRefGoogle Scholar
  20. 20.
    Platz EA, De Marzo AM (2004) Epidemiology of inflammation and prostate cancer. J Urol 271:36–40CrossRefGoogle Scholar
  21. 21.
    Srivastava K, Srivastava A, Kumar A, Mittal B (2010) Significant association between toll-like receptor gene polymorphisms and gallbladder cancer. Liver Int 30:1067–1072PubMedCrossRefGoogle Scholar
  22. 22.
    Noguchi E, Nishimura F, Fukai H, Kim J, Ichikawa K, Shibasaki M et al (2004) An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population. Clin Exp Allergy 34:177–183PubMedCrossRefGoogle Scholar
  23. 23.
    He JF, Jia WH, Fan Q, Zhou XX, Qin HD, Shugart YY et al (2007) Genetic polymorphisms of TLR3 are associated with Nasopharyngeal carcinoma risk in Cantonese population. BMC Cancer 7:194PubMedCrossRefGoogle Scholar
  24. 24.
    Etokebe GE, Knezević J, Petricević B, Pavelić J, Vrbanec D, Dembić Z (2009) Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in case-control study with breast cancer. Genet Test Mol Biomarkers 13:729–734PubMedCrossRefGoogle Scholar
  25. 25.
    Hold GL, Rabkin CS, Gammon MD, Berry SH, Smith MG, Lissowska J et al (2009) CD14-159C/T and TLR9-1237T/C polymorphisms are not associated with gastric cancer risk in Caucasian populations. Eur J Cancer Prev 18:117–119PubMedCrossRefGoogle Scholar
  26. 26.
    Mollaki V, Georgiadis T, Tassidou A, Ioannou M, Daniil Z, Koutsokera A et al (2009) Polymorphisms and haplotypes in TLR9 and MYD88 are associated with the development of Hodgkin’s lymphoma: a candidate-gene association study. J Hum Genet 54:655–659PubMedCrossRefGoogle Scholar
  27. 27.
    Tsan MF (2006) Toll-like receptors, inflammation, and cancer. Semin Cancer Biol 16:32–37PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Raju K. Mandal
    • 1
  • Ginu P. George
    • 1
  • Rama D. Mittal
    • 1
  1. 1.Department of Urology and Renal TransplantationSanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia

Personalised recommendations