Abstract 3235: Pre-diagnosis neutrophil-to-lymphocyte ratio and lung cancer risk in heavy smokers
Authors: Grieshober Laurie , Graw Stefan , Barnett Matt J. , Thornquist Mark D. , Goodman Gary E. , Chen Chu , Koestler Devin C. , Marsit Carmen J. , Doherty Jennifer A. 
Published: August 2018

Abstract
The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that is inversely associated with survival for many chronic diseases, including lung cancer. We hypothesize that the inflammatory profile reflected by DNA methylation-derived NLR (mdNLR) may also be associated with lung cancer risk. We assessed the relationship between pre-diagnosis mdNLR and lung cancer risk in a nested case-control study of the β-Carotene and Retinol Efficacy Trial (CARET), a population at high risk for lung cancer due to heavy smoking (≥20 pack years; current smoker or quit ≤6 years before enrollment) or substantial occupational asbestos exposure (current smoker or quit ≤15 years before enrollment). We matched 319 incident lung cancer cases to controls based on time at risk, age at blood draw, smoking status, sex, race, asbestos exposure, and enrollment year. We computed mdNLR using the ratio of predicted neutrophil and lymphocyte proportions derived from DNA methylation signatures in whole blood samples collected prior to diagnosis (mean 4.31 years in cases). Conditional logistic regression models were adjusted for potential confounding factors: age, pack years of smoking, cigarettes per day, and body mass index. Mean mdNLR was higher in cases at 2.06 than in controls at 1.86 (p=0.04). Each unit increase in mdNLR was associated with a 21% increased risk of lung cancer (Odds Ratio (OR) 1.21, 95% Confidence Interval (CI) 1.01-1.45). There was a 30% increased risk of non-small cell lung cancer (NSCLC; n=240 pairs; 1.30, 1.03-1.63); estimates for adenocarcinoma and squamous cell NSCLC were similar. mdNLR was not associated with small cell lung cancer (n=68 pairs; 1.06, 0.77-1.47). The association between mdNLR and NSCLC risk was most pronounced in those with asbestos exposure (3.39, 1.32-8.67; all men). Estimates for NSCLC cases without asbestos exposure were similar for men (1.15, 0.88-1.51) and women (1.22, 0.75-1.98). We assessed whether mdNLR and NSCLC risk associations varied by tertiles of time at risk among cases: 0-2.7 years, 2.8-5.4 years, and 5.5-9.8 years. Though NSCLC risk was suggestively elevated in each time period stratum, the magnitude of the association was largest for the time period closest to diagnosis (1.49, 0.92-2.41; 1.26, 0.86-1.84; and 1.30, 0.88-1.91, respectively). This is the first study to evaluate whether pre-diagnosis mdNLR is associated with lung cancer risk, and we assessed this association in a sample of heavy smokers. Our findings suggest that the inflammatory response produced by both smoking and asbestos may be reflected by mdNLR. A better understanding of the role of mdNLR in NSCLC etiology may improve detection of nascent lung cancer, thereby improving treatment strategies in NSCLC patients.
Citation Format: Laurie Grieshober, Stefan Graw, Matt J. Barnett, Mark D. Thornquist, Gary E. Goodman, Chu Chen, Devin C. Koestler, Carmen J. Marsit, Jennifer A. Doherty. Pre-diagnosis neutrophil-to-lymphocyte ratio and lung cancer risk in heavy smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3235.