Abstract

Inflammation is hypothesized to play a role in colorectal tumorigenesis. Circulating levels of C-reactive protein (CRP), a serologic marker of the inflammatory response, have been positively associated with colorectal cancer development in some studies; however, there are limited data on the relation of CRP with colorectal adenomas, established precursors of colorectal cancer. A nested case-control investigation of CRP levels and incident colorectal adenoma was conducted in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized trial of 154,942 individuals designed to test the efficacy of flexible sigmoidoscopy on colorectal cancer mortality when performed once, and then repeated 3 to 5 years later. Serum CRP levels were measured in baseline blood specimens from participants who were free of polyps in the left-sided colorectum at the baseline screening procedure, but who were found at the subsequent screen to have at least one colorectal adenoma (n=356), and in a set of polyp-free, frequency-matched controls (n=396). In a multivariable logistic regression model that included established colorectal adenoma risk factors, a 1-unit increase in log CRP level was associated with a 15% reduction in risk of developing colorectal adenoma (OR=0.85, 95% CI, 0.75-0.98, Ptrend=0.01). This association did not differ according to body size, smoking behavior, gender, use of nonsteroidal antiinflammatory drugs, or adenoma location. High circulating CRP levels may be protective against colorectal adenoma development. Though at contrast with mechanistic data on inflammation and colorectal tumorigenesis, this finding is not inconsistent with prior results on CRP and colorectal adenoma and warrants further investigation.

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