Association between C-reactive protein, incident liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case-control study.

Abstract

C-reactive protein (CRP) is a marker of systemic inflammation that has been associated with the incidence and prognosis for a number of different cancers. Recent data suggest that CRP may be a prognostic factor for liver cancer and cirrhosis. However, few long-term studies are available. We prospectively examined associations between serum CRP and subsequent risk of liver cancer incidence or chronic liver disease mortality in a nested case-control study performed in the Linxian Nutrition Intervention Trials cohort. Baseline serum CRP was measured for 220 incident liver cancer cases, 276 participants who died of chronic liver disease, and 1,018 age-, sex-, and trial-matched controls. Unconditional logistical regression models were used to estimate ORs and 95% confidence intervals (CI). Compared with the lowest quartile, subjects in the fourth quartile of serum CRP had a higher risk of liver cancer incidence (OR, 1.63; 95% CI, 1.06-2.51), with a significant Ptrend across quartiles (P = 0.01). The association with liver cancer was only significant among men (Q4 vs. Q1; OR, 2.00; 1.10-3.62), but not among women (Q4 vs. Q1; OR, 1.15; 0.60-2.22). For chronic liver disease deaths, the corresponding risk estimate in men and women was 2.95 (1.90-4.57), with a monotonic trend (P < 0.001). Higher serum CRP concentrations at baseline were associated with subsequent incidence of liver cancer and death from chronic liver disease. Our findings suggest that levels of systemic inflammation may serve as a long-term marker of liver cancer and liver disease.