Abstract 2789: C-reactive protein and risk of lung cancer

Abstract

Abstract Background: Chronic inflammation could act as a co-factor to tobacco smoke in increasing lung cancer risk, underscoring the potential for both lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP) and CRP single nucleotide polymorphisms (SNPs) with prospective risk of lung cancer. Methods: We conducted a nested case-control study of 592 lung cancers and 670 controls with available pre-diagnostic serum and 378 cases and 447 controls with available DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N=77,464). Controls were matched to cases on age, sex, entry year, follow-up time, and smoking status (cumulative amount and time since quitting). We measured CRP levels in baseline serum samples and genotyped 5 common CRP SNPs. Results: Elevated CRP levels were associated with increased lung cancer risk (odds ratio [OR] for individuals in the fourth quartile (Q4, ≥5.6 mg/L) vs. those in Q1 (<1.0 mg/L)=1.98; 95% CI=1.35-2.89), with a trend for increasing risk across CRP quartiles (p-trend<0.001). This association was most apparent for squamous cell carcinomas (OR=2.92; 95% CI=1.30-6.54), in the 2-5 years before lung cancer diagnosis (OR=2.33; 95% CI=1.24-4.39), and among former (OR=2.48; 95% CI=1.53-4.03) and current smokers (OR=1.90; 95% CI=1.06-3.41). Although CRP SNPs and haplotypes were associated with significant differences in CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels, among both former (Q4=2.55% vs. Q1=1.39%) and current smokers (Q4=7.37% vs. Q1=4.03%). Conclusions: Elevated CRP levels are associated with subsequently increased lung cancer risk, in support of an etiologic role for chronic pulmonary inflammation in lung carcinogenesis. The separation in lung cancer absolute risks across circulating CRP levels among former and current smokers provides preliminary evidence for the utility of CRP measurements in lung cancer risk stratification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2789.