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C-Reactive Protein Levels, Variation in the C-Reactive Protein Gene, and Cancer Risk: The Rotterdam Study

Claire Siemes, Loes E. Visser, Jan-Willem W. Coebergh, Ted A.W. Splinter, Jacqueline C.M. Witteman, André G. Uitterlinden, Albert Hofman, Huibert A.P. Pols, Bruno H.Ch. Stricker

From the Departments of Epidemiology & Biostatistics, Internal Medicine, and Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands

Address reprint requests to Bruno H.Ch. Stricker, MB, PhD, Department of Epidemiology & Biostatistics, Erasmus University Medical Center, PO Box 2040, 3000 DR Rotterdam, the Netherlands; e-mail: b.stricker{at}erasmusmc.nl

Purpose It remains unclear if inflammation itself may induce cancer, if inflammation is a result of tumor growth, or a combination of both exists. The aim of this study was to examine whether C-reactive protein (CRP) levels and CRP gene variations were associated with an altered risk of colorectal, lung, breast, or prostate cancer.

Patients and Methods A total of 7,017 participants age 55 years from the Rotterdam Study were eligible for analyses. Mean follow-up time was 10.2 years. High-sensitivity CRP measurements were performed to identify additional values of 0.2 to 1.0 mg/L compared with standard procedures. Genotypes of the CRP gene were determined with an allelic discrimination assay.

Results High levels (> 3 mg/L) of CRP were associated with an increased risk of incident cancer (hazard ratio, 1.4; 95% CI, 1.1 to 1.7) compared with persons with low levels (< 1 mg/L), even after a potential latent period of 5 years was introduced. Although CRP seems to affect several cancer sites, the association was strongest for lung cancer (hazard ratio, 2.8; 95% CI, 1.6 to 4.9). A CRP single nucleotide polymorphism associated with decreased CRP levels was associated with an increased lung cancer risk of 2.6 (95% CI, 1.6 to 4.4) in homozygous carriers.

Conclusion Baseline CRP levels seem to be a biomarker of chronic inflammation preceding lung cancer, even after subtracting a 5-year latent period. Furthermore, CRP gene variation associated with low CRP blood levels was relatively common in patients with lung cancer. Both chronic inflammation and impaired defense mechanisms resulting in chronic inflammation might explain these results.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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