C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study.
OBJECTIVE
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.


METHODS
A total of 7,017 participants age > or = 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.


CONCLUSIONS
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.
Siemes
Claire
C
Department of Epidemiology & Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Visser
Loes E
LE
Coebergh
Jan-Willem W
JW
Splinter
Ted A W
TA
Witteman
Jacqueline C M
JC
Uitterlinden
André G
AG
Hofman
Albert
A
Pols
Huibert A P
HA
Stricker
Bruno H Ch
BH
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000453:epidemiology; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D002908:Chronic Disease; D015179:Colorectal Neoplasms / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000097:blood; D008175:Lung Neoplasms / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000453:epidemiology; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors
D014408:Biomarkers, Tumor; D002097:C-Reactive Protein