Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer

• Type of Material: Article
• Authors: Laurie Grieshober, University of Utah; Stefan Graw, Emory University; Matt J Barnett, Fred Hutchinson Cancer Research Center; Gary E Goodman, Fred Hutchinson Cancer Research Center; Chu Chen, Fred Hutchinson Cancer Research Center; Devin C Koestler, University of Kansas; Carmen Marsit, Emory University; Jennifer A Doherty, University of Utah
• Language: English
• Date: 2021-07-08
• Publisher: SPRINGER
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s10552-021-01469-3
• Title of Journal or Parent Work: CANCER CAUSES & CONTROL
• Volume: 32
• Issue: 11
• Start Page: 1227
• End Page: 1236
• Grant/Funding Information: The research reported in this publication was supported by the National Center for Advancing Translational Sciences (NCATS) of the NIH under Award Number TL1 TR002540 and the National Cancer Institute (NCI) of the NIH R01 CA151989 (to J.A. Doherty), the Munck-Pfefferkorn Fund at Dartmouth College (to J.A. Doherty and C.J. Marsit), the Huntsman Cancer Foundation (to J.A. Doherty), and the Kansas IDeA Network of Biomedical Research Excellence Bioinformatics Core (to D.C. Koestler), and supported in part by the National Institute of General Medical Science (NIGMS) award P20 GM103418 (to D.E. Wright), and the NCI under award numbers P30 CA042014 (to M.E. Beckerle), P30 CA168524 (to R.A. Jensen), and R01 CA111703 (to C. Chen). Support for CARET is from NCI grants UM1 CA167462 and U01 CA63673 (to G.E. Goodman) and U01 CA167462 (to C. Chen). The funding bodies had no roles in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: DISEASE; Mortality; PROGNOSIS; METAANALYSIS; Public, Environmental & Occupational Health; EMPHYSEMA; RISK-FACTORS; Oncology; INFLAMMATION; Science & Technology; NEUTROPHIL/LYMPHOCYTE; Life Sciences & Biomedicine; SMOKING; HOMEOSTASIS; NLR; Lung cancer; Non-small cell lung cancer; DNA METHYLATION; Methylation; Small cell lung cancer
• Research Categories: Health Sciences, Public Health; Biology, Biostatistics; Health Sciences, Oncology; Health Sciences, Epidemiology

Abstract

Purpose: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods: We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results: Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion: Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.