Abstract 3632: The relationships between c-reactive protein, smoking, and lung cancer mortality in the Third National Health and Nutrition Examination Survey.
Authors: Bittoni Marisa A. , Harris Randall E. , Clinton Steven K. , Focht Brian C. 
Published: August 2014

Background: Chronic inflammation plays an important role in carcinogenesis for several cancers. C-reactive protein (CRP) is an acute-phase protein that displays a rapid and distinct rise in its plasma concentration in response to acute inflammation, infection and tissue damage. CRP levels have been found to be moderately elevated in individuals with chronic inflammatory diseases, including lung cancer. Few studies have examined associations between lung cancer, CRP, smoking, and other inflammatory factors. The purpose of this study was to examine serum CRP, smoking, obesity, and serum vitamin D levels in relation to lung cancer mortality. It was hypothesized that increased serum CRP levels, smoking, obesity and decreased serum vitamin D levels would result in increased lung cancer mortality.

Methods: Data from cancer-free individuals over age 40 in the Third National Health and Nutrition Examination Survey (NHANESIII:1988-1994) were examined prospectively in relation to inflammatory factors and lung cancer mortality. Mortality status was ascertained through probabilistic record matching using the National Death Index, with mortality follow-up through 2006. Baseline demographic and clinical data were acquired from interviews and laboratory examinations. Cox proportional hazards regression models were used to assess factors related to inflammation and lung cancer mortality.

Results: Of 10,735 participants, 219 individuals died of lung cancer during follow-up. Individuals who died from lung cancer were significantly more likely to be male (67% vs 47%), non-white (34% vs 27%), older (65 vs 62 years), to have elevated serum CRP levels (&gt;3mg/L; 41% vs 33%), lower mean BMI (26 vs 28 kg/m2), and to have ever smoked &gt;100 cigarettes (94% vs 54%) than lung cancer survivors. Mean serum vitamin D levels were similar for both groups (25.4 ng/ml). Multivariate regression analysis revealed greater lung cancer mortality risk for elevated CRP levels when adjusting for age, gender, BMI and ever having smoked (HR=1.80; p&lt;0.001). The lung cancer mortality risk for smokers increased 10-fold when adjusting for other factors (p&lt;0.0001). Also, lung cancer mortality risk increased with older age and male gender (HR=1.05 and 1.45;p&lt;0.01, respectively), but higher BMI levels showed a slightly protective effect (HR=0.92;p&lt;0.0001).

Conclusions: The multivariate models in this study showed associations between elevated CRP and lung cancer mortality risk even when adjusting for other factors related to inflammation, such as obesity and smoking. The lung cancer mortality risk for smokers increased 10-fold when adjusting for other factors, whereas higher obesity levels showed a protective effect. Future studies should further explore CRP as a biomarker of lung cancer risk and mechanisms that mediate the CRP-lung cancer relationship, such as obesity, diet and smoking.

Citation Format: Marisa A. Bittoni, Randall E. Harris, Steven K. Clinton, Brian C. Focht. The relationships between c-reactive protein, smoking, and lung cancer mortality in the Third National Health and Nutrition Examination Survey. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3632. doi:10.1158/1538-7445.AM2013-3632