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

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 372 lung cancer 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 those who developed small cell lung cancer (SCLC, N = 81), individuals 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 in SCLC (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). mdNLR was not associated with mortality for individuals diagnosed with adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115).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 other lung cancer histotypes.

Methylation-derived Inflammatory Measures and Lung Cancer Risk and Survival

“…Our study is not directly comparable to prior studies since we measured mdNLR using blood samples from subjects with a median of 14 years prior to lung cancer diagnosis. To our knowledge, only one other cohort, the multicenter β-Carotene and Retinol Efficacy Trial (CARET), examined pre-diagnosis mdNLR and lung cancer risk and survival using blood drawn years prior to diagnosis (median 4.7 years) (29, 30). In this study of heavy smokers from CARET, researchers reported a 21% increased risk of lung cancer per one standard deviation increase in mdNLR (OR: 1.21 [1.01, 1.45]), a 30% increased risk of NSCLC for one standard deviation increase in mdNLR (OR: 1.30 [1.03, 1.63], and no association between higher pre-diagnosis mdNLR and risk of developing SCLC (OR: 1.06 [0.77, 1.47]) (29).…”

“…CARET researchers recently reported that pre-diagnosis mdNLR is positively associated with increased mortality for SCLC cases, but not for other case types (30). In comparison, we observed a positive association between pre-diagnosis mdNLR and lung cancer-specific and NSCLC-specific mortality.…”