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Original Contribution
JAMA. 2004;291(5):585-590. doi: 10.1001/jama.291.5.585

C-Reactive Protein and the Risk of Incident Colorectal Cancer

  1. Thomas P. Erlinger, MD, MPH;
  2. Elizabeth A. Platz, ScD, MPH;
  3. Nader Rifai, PhD;
  4. Kathy J. Helzlsouer, MD, MHS
  1. Author Affiliations: Department of Medicine (Drs Erlinger and Helzlsouer) and Sidney Kimmel Comprehensive Cancer Center (Dr Platz), Johns Hopkins Medical Institutions, and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health (Drs Erlinger, Platz, and Helzlsouer), Baltimore, Md; and Department of Pathology, Harvard Medical School, and Department of Laboratory Medicine, Children's Hospital, Boston, Mass (Dr Rifai).

Abstract

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.

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