Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis
- 993 Downloads
We investigated the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) with cancer risk.
We examined the associations of CRP and IL-6 with incident cancer in two prospective cohorts, the British Women’s Heart and Health Study (4,286 women aged 60–80) and the Caerphilly Cohort (2,398 men aged 45–59) using Cox regression and pooled our findings with previous prospective studies’ in fixed and random effects meta-analyses.
CRP and IL-6 were associated with some incident cancers in our cohorts, but the numbers of cancer cases were small. In our meta-analyses elevated CRP was associated with an increased overall risk of cancer (random effects estimate (RE): 1.10, 95% CI: 1.02, 1.18) and lung cancer (RE: 1.32, 95% CI: 1.08, 1.61). Its associations with colorectal (RE: 1.09, 95% CI: 0.98, 1.21) and breast cancer risks (RE: 1.10, 95% CI: 0.97, 1.26) were weaker. CRP appeared unrelated to prostate cancer risk (RE: 1.00 0.88, 1.13). IL-6 was associated with increased lung and breast cancer risks and decreased prostate cancer risk, and was unrelated to colorectal cancer risk.
Our findings suggest an etiological role for CRP and IL-6 in some cancers. Further large prospective and genetic studies would help to better understand this role.
KeywordsCancer Inflammation C-reactive protein Interleukin-6 Meta-analysis
The BWHHS is co-directed by Peter Whincup and Goya Wannamethee in addition to Shah Ebrahim and Debbie Lawlor. We thank Rita Patel, Carol Bedford, Alison Emerton, Nicola Frecknall, Karen Jones, Mark Taylor, Simone Watson, and Katherine Wornell for collecting and entering data; all the general practitioners and their staff who have supported data collection; and the women who have participated in the study. We also thank Karen Craig, Estelle Poorhang, and Paul Welsh for technical assistance with the CRP and IL-6 assays. The BWHHS is funded by the Department of Health. Grants from the British Heart Foundation supported CRP and IL6 assays. Debbie Lawlor is funded by a (UK) Department of Health career scientist award and when this work was conducted, Katriina Heikkilä was funded by the (UK) Medical Research Council PhD Studentship.
Conflict of interest
None declared. The views expressed in this paper are those of the authors and not necessarily those of any funding body.
- 16.MRC Epidemiology Unit C (2007) Caerphilly prospective study. Department of Social Medicine, University of BristolGoogle Scholar
- 26.Lawlor DA, Davey Smith G, Rumley A, Lowe GD, Ebrahim S (2005) Associations of fibrinogen and C-reactive protein with prevalent and incident coronary heart disease are attenuated by adjustment for confounding factors. British Women’s Heart and Health Study. Thromb Haemost 93(5):955–963PubMedGoogle Scholar
- 30.Berg J, Fellier H, Christoph T, Grarup J, Stimmeder D (1999) The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res 48(7):369–379. doi: 10.1007/s000110050474 PubMedCrossRefGoogle Scholar
- 31.Gonzalez E, de la Cruz CC, de Nicolas NR, Egido J, Herrero-Beaumont G (1994) Long-term effect of nonsteroidal anti-inflammatory drugs on the production of cytokines and other inflammatory mediators by blood cells of patients with osteoarthritis. Agents Actions 41(3–4):171–178. doi: 10.1007/BF02001912 PubMedCrossRefGoogle Scholar
- 39.MRC Unit (South Wales) (1985) The Caerphilly Collaborative Heart Disease Study Project Description and Manual of Operations. MRC Unit, South WalesGoogle Scholar
- 42.Otani T, Iwasaki M, Sasazuki S, Inoue M, Tsugane S (2006) Plasma C-reactive protein and risk of colorectal cancer in a nested case–control study: Japan Public Health Center-based prospective study. Cancer Epidemiol Biomarkers Prev 15(4):690–695. doi: 10.1158/1055-9965.EPI-05-0708 PubMedCrossRefGoogle Scholar
- 50.Llorca J, Lopez-Diaz MJ, Gonzalez-Juanatey C, Ollier WE, Martin J, Gonzalez-Gay MA (2007) Persistent chronic inflammation contributes to the development of cancer in patients with rheumatoid arthritis from a defined population of northwestern Spain. Semin Arthritis Rheum 37(1):31–38. doi: 10.1016/j.semarthrit.2007.01.002 PubMedCrossRefGoogle Scholar
- 68.Weinberg RA (2007) Crowd control: tumour immunology and immunotherapy. In: The biology of cancer, 1st edn. Garland Science, Taylor and Francis Group, LLC Google Scholar