Gunter MJ, Stolzenberg-Solomon R, Cross AJ, et al. A prospective study of serum C-reactive protein and colorectal cancer risk in men

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland 20852, USA.
Cancer Research (Impact Factor: 9.33). 03/2006; 66(4):2483-7. DOI: 10.1158/0008-5472.CAN-05-3631
Source: PubMed


Chronic inflammation has been implicated in the etiology of colorectal cancer. C-reactive protein (CRP), a sensitive marker of inflammation, has been investigated with regard to colorectal cancer in only three previous studies, and the results from these investigations were inconsistent. We examined serum CRP levels in relation to colorectal cancer incidence in a nested case-control study within the Alpha Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 Finnish males enrolled from 1985 to 1988 with follow-up through April 2002. Colorectal cancer cases were ascertained by the Finnish Cancer Registry; this analysis included 130 cases of colorectal cancer (with available blood), which occurred between 1990 and April 30, 2002, and 260 matched controls. Baseline median CRP levels were approximately 25% higher among colorectal cancer cases (3.4 mg/L) than controls (2.6 mg/L; P = 0.04). Relative to men in the lowest quartile of CRP concentration, men in the highest quartile had an odds ratio of 2.9 (95% confidence interval, 1.4-6.0) for developing colorectal cancer with a dose-response relationship supported (P(trend) = 0.006). The relation between CRP and incident colorectal cancer was modified by body mass index such that the association was stronger among lean individuals than in heavier individuals (P(interaction) = 0.018). These results support the notion that chronic low-grade inflammation is a marker for increased risk of colorectal cancer.

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Available from: Richard J Wood, Apr 23, 2014
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    • "Chronic inflammation is considered a risk factor for many common malignancies including cancers of the breast[1], lung[2], and colon[3]. Colorectal cancer is the third most common type of cancer and the third leading cause of cancer-associated mortality in both males and females in the United States[4]. "
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    ABSTRACT: Necroptosis, a novel form of programmed cell death, was recently shown to be strongly associated with intestinal inflammation in mice and in pediatric patients with inflammatory bowel disease (IBD). Persistent inflammation of the colon is an important risk factor for colorectal cancer. Necrostatin-1 (Nec-1), known as a specific inhibitor of necroptosis, through preventing the receptor-interacting protein (RIP) 1 and RIP3 interaction. In the present study, the anti-inflammatory and antitumorigenic efficacy of necrostatin-1 was studied in mouse models of colitis and colitis-associated cancer (CAC). We found that in acute dextran sulfate sodium (DSS)-induced colitis, treatment with necrostatin-1 significantly suppressed colitis symptoms in mice, including weight loss, colon shortening, colonic mucosa damage and severity, and excessive production of interleukin-6. Necrostatin-1 administration inhibited the upregulation of RIP1 and RIP3 and enhanced the expression of caspase-8 in DSS-induced colitis. In addition, the anti-inflammatory effect of necrostatin-1 was confirmed by in vitro analyses. Necrostatin-1 treatment reduced the production of proinflammatory cytokine and extracellular HMGB1 release in HT-29 cells in active necroptosis. Furthermore, In a mouse model of colitis-associated tumorigenesis, necrostatin-1 administration significantly suppressed tumor growth and development through inhibiting JNK/c-Jun signaling. Taken together, these findings suggest that necrostatin-1 might be a promising therapeutic option for the treatment of colitis-associated colorectal cancer in patients with IBD.
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    • "Cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) were found to decrease the incidence of colorectal adenoma, and NSAIDs were also found to reduce the incidence of CRC [4]. Elevated C-reactive protein (CRP), which is a marker of systemic inflammation was reported as the risk factor for CRC [5]. "
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    ABSTRACT: Purpose This study was conducted to evaluate the systemic inflammatory response in colorectal cancer patients, and to estimate the usefulness of the Glasgow prognostic score (GPS) as a prognostic factor. Methods Patients with biopsy-proven colorectal adenocarcinoma who were operated between April 2005 and December 2008 were enrolled in this study. The GPS was estimated based on the measurement of CRP and serum albumin level. The GPS was compared with other clinicopathological factors. Univariate and multivariate analyses were performed to evaluate the factors affecting cancer-specific survival. Results GPS was significantly higher in patients with anemia, thrombocytosis, a high neutrophil to lymphocyte ratio, tumor of the colon, and large tumor. Patient age, gender, serum CEA level, tumor gross appearance, TNM stage, and tumor differentiation were not related with the GPS. In univariate analysis, hemoglobin, CEA, gross appearance of tumor, TNM stage, tumor differentiation, and GPS were associated with cancer-specific survival. In multivariate analysis, TNM stage (III or IV : I or II; hazard ratio [HR], 12.322; P = 0.015), tumor differentiation (poorly differentiated : well or moderately differentiated; HR, 3.112; P = 0.021), and GPS (GPS 2 : GPS 0 or 1; HR, 5.168; P = 0.003) were identified as independent prognostic factors in colorectal cancer. Conclusion Our study showed that the GPS was an independent variable from tumor stage and a good and convenient prognostic factor in colorectal cancer patients.
    Full-text · Article · Jun 2014 · Annals of Surgical Treatment and Research
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    • "These results suggest the predictable potency of CRP in the mortality of CRC patients. Therefore, the results of the present study to a certain extent confirmed the conclusions of a number of previous studies which considered the positive pathological role of CRP in CRC (32–34,43). Possible reasons for the difference between the previous studies which indicated a negative association between CRP levels and clinical and pathological features in CRC patients, and other previous positive studies including the present one are probably partly attributable to the variable potential biological features, different stages, distribution of the patient population and the disparate territory. "
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    ABSTRACT: Elevated levels of C-reactive protein (CRP) have been described as a prognostic factor in various types of human malignancy. In the present study, the prognostic potency of CRP was validated for patients with colorectal cancer (CRC) in order to guide patient management and define high-risk populations for follow-up or for therapeutic purposes. The association between the high sensitivity-CRP (hs-CRP) levels of a total of 123 patients with CRC and their clinicopathological characteristics was explored. Subsequently, univariate and multivariate analyses were performed to investigate the survival impact of pre-treatment hs-CRP levels in this cohort study. Statistically significant correlations between the serum levels of hs-CRP and lymph node and distant metastasis (P<0.001 and P=0.012, respectively), vascular and perineural invasion (P<0.001 and P<0.001), grades (P=0.022) and clinical stages (P=0.001), but not age and gender (P=0.616 and 0.676, respectively), were found. The five-year survival rate of patients with elevated (>5.0 mg/l) hs-CRP levels was demonstrated to be significantly less than that of those in the normal group (≥5.0 mg/l) by applying the Kaplan-Meier method (13.3 versus 57.0%, log-rank test P<0.001). Furthermore, following identification as a prognostic factor through using univariate analysis, high levels of hs-CRP (P<0.001) were validated as an independent prognosticator in CRC in the present study through using multivariate analysis. Pre-treatment serum CRP levels were associated with advanced and progressed CRC patients, therefore these levels may serve as a potential prognostic marker for CRC patients.
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