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C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older

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Abstract

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (−174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03–2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation.

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References

  1. Sutcliffe S, Platz EA (2007) Inflammation in the etiology of prostate cancer: an epidemiologic perspective. Urol Oncol 25:242–249. doi:10.1016/j.urolonc.2006.09.014

    PubMed  CAS  Google Scholar 

  2. De Marzo AM, Platz EA, Sutcliffe S et al (2007) Inflammation in prostate carcinogenesis. Nat Rev Cancer 7:256–269. doi:10.1038/nrc2090

    Article  PubMed  CAS  Google Scholar 

  3. Dennis LK, Lynch CF, Torner JC (2002) Epidemiologic association between prostatitis and prostate cancer. Urology 60:78–83. doi:10.1016/S0090-4295(02)01637-0

    Article  PubMed  Google Scholar 

  4. Dennis LK, Dawson DV (2002) Meta-analysis of measures of sexual activity and prostate cancer. Epidemiology 13:72–79. doi:10.1097/00001648-200201000-00012

    Article  PubMed  Google Scholar 

  5. Sun J, Turner A, Xu J, Gronberg H, Isaacs W (2007) Genetic variability in inflammation pathways and prostate cancer risk. Urol Oncol 25:250–259. doi:10.1016/j.urolonc.2006.10.001

    PubMed  CAS  Google Scholar 

  6. Platz EA, De Marzo AM (2004) Epidemiology of inflammation and prostate cancer. J Urol 171:S36–S40. doi:10.1097/01.ju.0000108131.43160.77

    Article  PubMed  Google Scholar 

  7. Latif Z, McMillan DC, Wallace AM et al (2002) The relationship of circulating insulin-like growth factor 1, its binding protein-3, prostate-specific antigen and C-reactive protein with disease stage in prostate cancer. BJU Int 89:396–399. doi:10.1046/j.1464-4096.2001.01641.x

    Article  PubMed  CAS  Google Scholar 

  8. Lehrer S, Diamond EJ, Mamkine B, Droller MJ, Stone NN, Stock RG (2005) C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer. BJU Int 95:961–962. doi:10.1111/j.1464-410X.2005.05447.x

    Article  PubMed  CAS  Google Scholar 

  9. McArdle PA, McMillan DC, Sattar N, Wallace AM, Underwood MA (2004) The relationship between interleukin-6 and C-reactive protein in patients with benign and malignant prostate disease. Br J Cancer 91:1755–1757. doi:10.1038/sj.bjc.6602211

    Article  PubMed  CAS  Google Scholar 

  10. Trautner K, Cooper EH, Haworth S, Ward AM (1980) An evaluation of serum protein profiles in the long-term surveillance of prostatic cancer. Scand J Urol Nephrol 14:143–149

    Article  PubMed  CAS  Google Scholar 

  11. Ward AM, Cooper EH, Houghton AL (1977) Acute phase reactant proteins in prostatic cancer. Br J Urol 49:411–418. doi:10.1111/j.1464-410X.1977.tb04168.x

    Article  PubMed  CAS  Google Scholar 

  12. Siemes C, Visser LE, Coebergh JW et al (2006) C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol 24:5216–5222. doi:10.1200/JCO.2006.07.1381

    Article  PubMed  CAS  Google Scholar 

  13. Platz EA, De Marzo AM, Erlinger TP et al (2004) No association between pre-diagnostic plasma C-reactive protein concentration and subsequent prostate cancer. Prostate 59:393–400. doi:10.1002/pros.10368

    Article  PubMed  CAS  Google Scholar 

  14. Licastro F, Candore G, Lio D et al (2005) Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2:8. doi:10.1186/1742-4933-2-8

    Article  PubMed  CAS  Google Scholar 

  15. Carlson CS, Aldred SF, Lee PK et al (2005) Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. Am J Hum Genet 77:64–77. doi:10.1086/431366

    Article  PubMed  CAS  Google Scholar 

  16. Lange LA, Carlson CS, Hindorff LA et al (2006) Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. JAMA 296:2703–2711. doi:10.1001/jama.296.22.2703

    Article  PubMed  CAS  Google Scholar 

  17. Paik JK, Kim OY, Koh SJ et al (2007) Additive effect of interleukin-6 and C-reactive protein (CRP) single nucleotide polymorphism on serum CRP concentration and other cardiovascular risk factors. Clin Chim Acta 380:68–74. doi:10.1016/j.cca.2006.11.011

    Article  PubMed  CAS  Google Scholar 

  18. Walston JD, Fallin MD, Cushman M et al (2007) IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study. Hum Genet 122(5):485–494

    Article  PubMed  CAS  Google Scholar 

  19. Wong LY, Leung RY, Ong KL, Cheung BM (2007) Plasma levels of fibrinogen and C-reactive protein are related to interleukin-6 gene -572C>G polymorphism in subjects with and without hypertension. J Hum Hypertens 21(11):875–882

    Article  PubMed  CAS  Google Scholar 

  20. Fishman D, Faulds G, Jeffery R et al (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376. doi:10.1172/JCI2629

    Article  PubMed  CAS  Google Scholar 

  21. Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275:18138–18144. doi:10.1074/jbc.M000379200

    Article  PubMed  CAS  Google Scholar 

  22. Fried LP, Borhani NO, Enright P et al (1991) The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1:263–276

    Article  PubMed  CAS  Google Scholar 

  23. Tell GS, Fried LP, Hermanson B, Manolio TA, Newman AB, Borhani NO (1993) Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol 3:358–366

    PubMed  CAS  Google Scholar 

  24. Cushman M, Cornell ES, Howard PR, Bovill EG, Tracy RP (1995) Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem 41:264–270

    PubMed  CAS  Google Scholar 

  25. Chen C, Lewis SK, Voigt L, Fitzpatrick A, Plymate SR, Weiss NS (2005) Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin. Cancer 103:76–84. doi:10.1002/cncr.20727

    Article  PubMed  CAS  Google Scholar 

  26. Johnson CH (ed) (2004) The SEER program coding and staging manual 2004, revision 1. NIH Pub. No. 04-5581. National Cancer Institute, Bethesda, MD

  27. Sieh W, Edwards KL, Fitzpatrick AL et al (2006) Genetic susceptibility to prostate cancer: prostate-specific antigen and its interaction with the androgen receptor (United States). Cancer Causes Control 17:187–197. doi:10.1007/s10552-005-0454-8

    Article  PubMed  Google Scholar 

  28. Young JL Jr, Roffers SD, Ries LAG, Fritz AG, Hurlbut AA (eds) (2001) The SEER program code manual—2000: coes and coding instructions. NIH Pub. No. 01-4969. National Cancer Institute, Bethesda, MD

  29. Lewis MR, Callas PW, Jenny NS, Tracy RP (2001) Longitudinal stability of coagulation, fibrinolysis, and inflammation factors in stored plasma samples. Thromb Haemost 86:1495–1500

    PubMed  CAS  Google Scholar 

  30. Harris TB, Ferrucci L, Tracy RP et al (1999) Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 106:506–512. doi:10.1016/S0002-9343(99)00066-2

    Article  PubMed  CAS  Google Scholar 

  31. Macy EM, Hayes TE, Tracy RP (1997) Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clin Chem 43:52–58

    PubMed  CAS  Google Scholar 

  32. Jenny NS, Tracy RP, Ogg MS et al (2002) In the elderly, interleukin-6 plasma levels and the -174G>C polymorphism are associated with the development of cardiovascular disease. Arterioscler Thromb Vasc Biol 22:2066–2071. doi:10.1161/01.ATV.0000040224.49362.60

    Article  PubMed  CAS  Google Scholar 

  33. Pearson TA, Mensah GA, Alexander RW et al (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:499–511. doi:10.1161/01.CIR.0000052939.59093.45

    Article  PubMed  Google Scholar 

  34. Brull DJ, Montgomery HE, Sanders J et al (2001) Interleukin-6 gene -174g>c and -572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 21:1458–1463. doi:10.1161/hq0901.094280

    Article  PubMed  CAS  Google Scholar 

  35. Kelberman D, Fife M, Rockman MV, Brull DJ, Woo P, Humphries SE (2004) Analysis of common IL-6 promoter SNP variants and the AnTn tract in humans and primates and effects on plasma IL-6 levels following coronary artery bypass graft surgery. Biochim Biophys Acta 1688:160–167

    PubMed  CAS  Google Scholar 

  36. Sun J, Hedelin M, Zheng SL et al (2004) Interleukin-6 sequence variants are not associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 13:1677–1679

    PubMed  CAS  Google Scholar 

  37. Tan D, Wu X, Hou M et al (2005) Interleukin-6 polymorphism is associated with more aggressive prostate cancer. J Urol 174:753–756. doi:10.1097/01.ju.0000168723.42824.40

    Article  PubMed  CAS  Google Scholar 

  38. Schaid DJ (2004) The complex genetic epidemiology of prostate cancer. Hum Mol Genet 13 Spec No 1:R103–R121

    Google Scholar 

  39. Zeegers MP, Jellema A, Ostrer H (2003) Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma: a meta-analysis. Cancer 97:1894–1903. doi:10.1002/cncr.11262

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors have no conflicts of interest to disclose. The authors would like to thank Dr. Leslie A. Lange and Elaine Cornell for their helpful suggestions related to this analysis. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. Financial Support: This work was supported by the training grant R25-CA94880, contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke.

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Correspondence to Brandon L. Pierce.

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This work was performed at the Institute for Public Health Genetics at the University of Washington and the Fred Hutchinson Cancer Research Center.

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Pierce, B.L., Biggs, M.L., DeCambre, M. et al. C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older. Cancer Causes Control 20, 1193–1203 (2009). https://doi.org/10.1007/s10552-009-9320-4

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  • DOI: https://doi.org/10.1007/s10552-009-9320-4

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