American Journal of Gastroenterology ISSN 0002-9270 C  2008 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2008.01952.x Published by Blackwell Publishing Elevation of C-Reactive Protein Level Is Associated With Synchronous and Advanced Colorectal Neoplasm in Men Han-Mo Chiu, M.D., 1,4,6 Jaw-Town Lin, Ph.D., 1,8 Tony H.-H. Chen, Ph.D., 7 Yi-Chia Lee, M.D., MSc., 1,4,7 Yueh-Hsia Chiu, Ph.D., 7 Jin-Tung Liang, M.D., Ph.D., 3 Chia-Tung Shun, M.D., Ph.D., 2 and Ming-Shiang Wu, M.D., Ph.D. 1,5 Departments of 1 Internal Medicine, 2 Pathology, 3 Surgery, 4 Health Management Center, and 5 Primary Care Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine; 6 Institute of Preventive Medicine, and 7 Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan; and 8 Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. (Am J Gastroenterol 2008;103:2317–2325) INTRODUCTION Colorectal cancer (CRC) is increasing worldwide and rep- resents a main cancer burden in Western countries as well as Asia (1). A majority of CRCs arise from colorectal ade- nomas via the well-known adenoma-to-carcinoma sequence (2). Accumulating evidence has indicated that the early detec- tion and removal of colorectal adenomas greatly reduces the mortality and incidence of CRC, and reliable detection and re- section of colorectal neoplasia before they become malignant Preliminary results of this study were presented in Digestive Disease Week 2007, Washington DC (Abstract S1987; Abstract published in Gastroenterology 2007; 32(Supp1):A293–4). is the underlying rationale for CRC screening (3). However, reliable biomarkers for both colorectal neoplasia are lacking and screening depends largely on the fecal occult blood test (FOBT) or endoscopy. Recently, evidence has accumulated that implicates a role for chronic inflammation in the pathogenesis of CRC (4). In- dividuals with inflammatory bowel disease (IBD) are at an increased risk for developing CRC (5), indicating that chronic inflammation may initiate genetic or epigenetic changes as- sociated with cancer development. Moreover, animal mod- els suggest that a continuous inflammatory state may pre- dispose to CRC (6), and epidemiologic observations have demonstrated that the long-term use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) reduce the occurrence of 2317