Background: Chronic inflammation has been implicated in the etiology of colorectal cancer (CRC), but epidemiologic findings on the association between circulating inflammatory markers and CRC risk are inconsistent. We hypothesized that increased concentrations of systemic inflammatory markers-white blood cell count (WBC), fibrinogen, von Willebrand factor (VWF), factor VIII (FVIII), and C-reactive protein (CRP)- and decreased albumin concentration would be associated with increased CRC risk in the Atherosclerosis Risk in Communities prospective cohort. Methods: WBC, fibrinogen, VWF, FVIII, and albumin, measured in 1987-1989 in 13,414 men and women, were transformed to z-scores and summed up to construct a blood "inflammation z-score." Albumin was included with a negative sign, because its concentration decreases with greater inflammation. A total of 308 incident CRC cases were identified through 2006 in initially cancer-free participants. CRP was measured in 1996-1998 in 9,836 cancer-free people who developed 166 CRCs through 2006. Proportional hazard models were used to estimate the HR and 95% CI of CRC in relation to each individual marker and the inflammation z-score. Results: After multivariate adjustment, for the highest versus lowest quartile, there was a statistically significant positive association of CRC risk with fibrinogen: HR = 1.50 (95% CI, 1.05-2.15), P = 0.03; inflammation z-score: HR = 1.65 (95% CI, 1.15-2.35), P = 0.01; and CRP: HR = 1.97 (95% CI, 1.13-3.43, P = 0.02. Conclusions: These findings indicate that greater levels of fibrinogen, CRP, and blood inflammation z-score are associated with increased CRC risk. Impact: The study provides further evidence that precancer inflammation may contribute to CRC etiology.
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