Context: Inflammation may play a role in the pathogenesis of colorectal cancer; however, epidemiological evidence supporting this hypothesis in average-risk persons is sparse.
Objective: To determine the risk of incident colon and rectal cancer associated with elevated baseline plasma concentrations of C-reactive protein (CRP).
Design, setting, and participants: Prospective, nested case-control study of a cohort of 22 887 adults (>18 years and Washington County, Maryland, residents) enrolled between May and October 1989 and followed up through December 2000. A total of 172 colorectal cancer cases were identified through linkage with the Washington County and Maryland State Cancer registries. Up to 2 controls (n = 342) were selected from the cohort for each case and matched by age, sex, race, and date of blood draw.
Main outcome measure: Odds ratio (OR) of incident colon and rectal cancer.
Results: Plasma CRP concentrations were higher among all colorectal cases combined than controls (median CRP, 2.44 vs 1.94 mg/L; P =.01). The highest concentration was found in persons who subsequently developed colon cancer vs matched controls (median CRP, 2.69 vs 1.97 mg/L; P<.001). Among rectal cancer cases, CRP concentrations were not significantly different from controls (median CRP, 1.79 vs 1.81 mg/L; P =.32). The risk of colon cancer was higher in persons in the highest vs lowest quartile of CRP (OR, 2.55; 95% confidence interval [CI], 1.34-4.88; P for trend =.002). In nonsmokers, the corresponding association was stronger (OR, 3.51; 95% CI, 1.64-7.51; P for trend<.001). A 1-SD increase in log CRP (1.02 mg/L) was associated with an increased risk of colon cancer after adjusting for potential confounders and excluding cases occurring within 2 years of baseline (OR, 1.35; 95% CI, 1.05-1.74) or excluding those with late-stage colon cancer at the time of diagnosis (OR, 1.38; 95% CI, 0.99-1.91).
Conclusions: Plasma CRP concentrations are elevated among persons who subsequently develop colon cancer. These data support the hypothesis that inflammation is a risk factor for the development of colon cancer in average-risk individuals.