Prospective evaluation of C-reactive protein, smoking and lung cancer death in the Third National Health and Nutrition Examination Survey

Chronic inflammation plays an important role in lung carcinogenesis. Few prospective studies have examined associations between lung cancer, serum C-reactive protein (CRP), a measure of systemic inflammation, and inflammatory lifestyle factors, such as smoking and obesity. This study prospectively examined the relationship between CRP and lung cancer death and its interrelationships with several lifestyle factors. Baseline data on smoking and other lifestyle variables were collected for 8,950 participants in the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994). Baseline CRP levels were measured in serum samples by nephelometry. Mortality status was ascertained through probabilistic record matching using the National Death Index through 2006. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for CRP and lung cancer death, with adjustment for smoking and other variables. During 18 years of follow-up, 219 individuals died from lung cancer. Multivariate regression models revealed a dose-response effect for elevated CRP and risk of lung cancer death when adjusting for age, gender, BMI and smoking. Compared to individuals with CRP <3 mg/l, lung cancer death was significantly associated with elevated levels of CRP: HR=1.63 (95% CI=1.15-2.26) for 3-7 mg/l and HR=2.44 (95% CI=1.81-3.45) for CRP >7 mg/l, P-trend <0.0001). The risk of lung cancer death for smokers increased 9-fold in adjusted models (P<0.0001). When stratified by gender and smoking status the effects of CRP were similar for smokers and males but did not reach statistical significance for females and non-smokers. This study supports a dose-dependent relationship between lung cancer death and CRP for males and smokers, but additional efforts are needed to better elucidate these relationships in women and non-smokers. The results suggest that CRP may emerge as a valuable tool in identifying high-risk subgroups of smokers for lung cancer prevention strategies.