C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older
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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.
KeywordsProstate cancer Inflammation C-reactive protein (CRP) Interleukin-6 (IL-6) IL-6 rs1800795 (−174)
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.
- 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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, MDGoogle 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, MDGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle Scholar
- 38.Schaid DJ (2004) The complex genetic epidemiology of prostate cancer. Hum Mol Genet 13 Spec No 1:R103–R121Google Scholar