Research Article Relationship between Biomarkers of Cigarette Smoke Exposure and Biomarkers of Inflammation, Oxidative Stress, and Platelet Activation in Adult Cigarette Smokers

Background: Cigarette smoking is a risk factor for several diseases, including cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, but the role of specific smoke constituents in these diseases has not been clearly established. Methods: The relationships between biomarkers of potential harm (BOPH), associated with inflammation [white blood cell (WBC), high sensitivity C-reactive protein (hs-CRP), fibrinogen, and von Willebrand factor (vWF)], oxidative stress [8-epi-prostaglandin F2a (8-epiPGF2a)] and platelet activation [11-dehydro-throm-boxin B2 (11-dehTxB2)], and machine-measured tar yields (grouped into four categories), biomarkers of exposure (BOE) to cigarette smoke: nicotine and its five metabolites (nicotine equivalents), 4-methylnitro-samino-1-(3-pyridyl)-1-butanol (total NNAL), carboxyhemoglobin, 1-hydroxypyrene, 3-hydroxypropylmer-capturic acid, andmonohydroxybutenyl-mercapturic acid, were investigated in 3,585 adult smokers and 1,077 nonsmokers. Results: Overall, adult smokers had higher levels of BOPHs than nonsmokers. Body mass index (BMI), smoking duration, tar category, and some of the BOEs were significant factors in the multiple regression models. Based on the F value, BMI was the highest ranking factor in the models for WBC, hs-CRP, fibrinogen, and 8-epiPGF2a, respectively, and gender and smoking duration for 11-dehTxB2 and vWF, respectively. Conclusions: Although several demographic factors and some BOEs were statistically significant in the model, the R2 values indicate that only up to 22 % of the variability can be explained by these factors, reflecting the complexity and multifactorial nature of the disease mechanisms. Impact: The relationships between the BOEs and BOPHs observed in this study may help with the identification of appropriate biomarkers and improve the design of clinical studies in smokers. Cancer Epidemiol Biomarkers Prev; 20(8); 1760–9. 2011 AACR