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Chronic inflammation has been implicated in the development of colorectal cancer (CRC). The presence of low-grade systemic inflammation, as determined by an elevation of high-sensitivity C-reactive protein (CRP), has been associated with an increased risk of cardiovascular diseases and cancers. However, previous studies of CRP and CRC in cohorts that comprised different genders have yielded conflicting results and little is known about CRP levels in individuals with colorectal adenomas, the precursor lesion of CRC. This study aims to elucidate the association of CRP and colorectal neoplasia.Plasma CRP levels were examined using a cross-sectional design in 6,695 consecutive ethnic Chinese adults who had undergone a complete colonoscopy following a thorough routine health evaluation. Logistic regression analysis was used to correlate the risk of colorectal neoplasia with CRP levels.Plasma CRP levels were significantly higher in subjects with colorectal neoplasia than in those without neoplasia (1.85 mg/L vs 1.55 mg/L, P= 0.04). The presence of synchronous neoplasia, advanced neoplasia, and concurrent synchronous and advanced neoplasia were associated with elevated levels of plasma CRP, after adjustment for other risk factors. Gender stratification revealed a positive association between elevated CRP levels and the risk of colorectal neoplasia in men, but no such corresponding association existed in women.Elevated plasma CRP levels are independently associated with an increased risk of colorectal neoplasia in men, but not in women. These data support the association between chronic inflammation and colorectal neoplasia in men and provide new insights into the underlying mechanisms that warrant further investigation.