Inflammatory biomarkers, aspirin, and risk of colorectal cancer: Findings from the physicians' health study.

BACKGROUND: Chronic inflammation has been implicated in colorectal carcinogenesis. However, the associations between plasma inflammatory markers and risk of colorectal cancer have been inconsistent. METHODS: In a nested case-control study in the Physicians' Health Study, we prospectively investigated the associations of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor receptor 2 (TNFR-2) with risk of colorectal cancer, and whether aspirin modified these associations among 268 colorectal cancer patients and 446 age- and smoking-matched controls. RESULTS: In multivariate-adjusted models, plasma levels of CRP, IL-6 and TNFR-2 were not significantly associated with risk of colorectal cancer, although a positive trend was observed for TNFR-2 (RR(highestvs.lowestquartile)=1.55; 95% CI=0.95-2.54; P(trend)=0.05). We observed a statistically significant association between elevated TNFR-2 levels and colorectal cancer risk in the placebo arm (RR(highestvs.lowesttertile)=1.77; 95% CI=1.02-3.06; P(trend)=0.02), but not in the aspirin arm (P(trend)=0.72). However, the interaction between TNFR-2 and aspirin was not statistically significant (P(interaction)=0.34). CONCLUSION: Plasma inflammatory markers were not significantly associated with colorectal cancer risk among men, though there was a statistically non-significant positive trend between TNFR-2 and colorectal cancer risk. More studies are required to understand the relationship between the role of TNFα pathway, aspirin, and colorectal cancer risk.