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

Abstract 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.