The Impact of Inflammation on the Incidence of Different Pathological Types of Lung Cancer: The Kailuan Study

Background Prior lung cancer studies on inflammatory indicators have examined single subtypes or aggregated types; however, there have been no systematic comparisons among major subtypes [adenocarcinoma (LUAD), squamous cell carcinoma (LUSC), small cell lung cancer (SCLC)]. The accuracy of novel indicators of incident lung cancer risk [systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI)] remains unexamined. Objective We aimed to assess associations of 15 inflammatory indicators (including SIRI and AISI) with both long-term and 10-year incident lung cancer risks, stratified by the pathological subtype. Methods and Results A prospective cohort of 99,925 cancer-free participants (mean age, 51.9 ± 12.7 years) was followed for 14.9 ± 3.1 years, identifying 1,804 incident lung cancers (317 LUAD, 215 LUSC, 138 SCLC, and 1,134 others). Multivariable analyses (using Cox or Fine-Gray models) showed that for each 1-Z score increase in several biomarkers, there was an associated increase in the long term hazard for lung cancer: Overall lung cancer HR increases : WBC (1.106), monocytes (1.058), lymphocytes (1.046), neutrophils (1.081), CLR (1.030), SIRI (1.535), AISI (1.068, stronger in men); LUSC HR increases : monocytes (1.102), MLR (1.026), PLR (1.063), SIRI (1.773), AISI (1.147), MHR (1.027). Long term Survival was not found to be associated with LUAD but showed an inverse association with SCLC [PLR (0.668)]. Notably, SIRI showed the strongest associations (+ 53.5% overall; +77.3% LUSC). Ten-year risk associations were generally stronger than long-term for most markers across subtypes. Conclusion Elevated inflammation elevates long-term overall lung cancer risk (particularly in men) and LUSC risk but not LUAD risk. PLR inversely associates with SCLC. Most indicators increase 10-year risk across all subtypes, with SIRI showing the strongest association.