Chronic inflammation has been implicated in colorectal carcinogenesis. Several studies have investigated the relationship between C-reactive protein (CRP), a biomarker of inflammation, and colorectal cancer and adenomas, resulting in inconsistent findings. The present study examined the relationship between circulating levels of high-sensitivity CRP and colorectal adenomas. The study subjects comprised 646 cases of colorectal adenoma and 635 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces. Statistical adjustment was made for cigarette smoking, alcohol use, body mass index, physical activity, and other potential confounders. The multivariate-adjusted geometric means showed no measurable differences between adenoma cases and controls, but were higher among cases with larger adenomas (trend P = 0.03). Likewise, although the prevalence odds of colorectal adenomas did not differ according to CRP levels as categorized at the 30th, 60th, and 90th percentiles in the controls, higher levels of CRP were associated with a statistically significant increase in the prevalence odds of large adenomas (> or = 5 mm), but not of small adenomas (<5 mm). The multivariate-adjusted odds ratios of large adenomas for the lowest to highest categories of CRP were 1.00 (referent), 1.81 (95% confidence interval 1.17-2.80), 1.61 (95% confidence interval 1.03-2.52), and 2.21 (95% confidence interval 1.28-3.84), respectively (trend P = 0.01). A positive association between CRP and prevalence odds of large adenomas was not modified by either smoking or overweight. These findings suggest that inflammation is linked to the growth of colorectal adenomas.