C-reactive protein and the risk of cancer: a mendelian randomization study.
Elevated plasma levels of C-reactive protein (CRP), a marker of inflammation, are associated with an increased risk of cancer, but it is unclear whether this association is causal. We examined whether four common single-nucleotide polymorphisms (SNPs) in the CRP gene that are associated with altered plasma CRP levels are causally associated with an increased risk of cancer. The study population included participants in a prospective study (n = 10 215) and a cross-sectional study (n = 36 403) of the adult general population in Denmark, all of whom were genotyped for the CRP SNPs. The association between plasma CRP levels measured by a high-sensitivity turbidimetry assay and the risk of cancer was examined for 8224 participants in the prospective study. The hazard ratio of cancer for a doubling of the plasma CRP level was 1.09 (95% confidence interval [CI] = 1.03 to 1.14). The nine most common genotype combinations of the four CRP SNPs were associated with up to a 72% increase (95% CI = 58% to 87%) in CRP levels but not with an increased risk of cancer. The estimated causal odds ratio for cancer associated with a genetically induced doubling in CRP level was 0.94 (95% CI = 0.81 to 1.08). This finding suggests that elevated CRP levels do not cause cancer.
Allin
Kristine H
KH
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Nordestgaard
Børge G
BG
Zacho
Jeppe
J
Tybjaerg-Hansen
Anne
A
Bojesen
Stig E
SE
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000453:epidemiology*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
D014408:Biomarkers, Tumor; D002097:C-Reactive Protein