The impact of inflammation on the incidence of different pathological types of lung cancer: the Kailuan study

Background: Chronic inflammation drives lung cancer pathogenesis; however, evidence on its association with incident risk across pathological subtypes remains limited. Objective: To evaluate associations of 15 inflammatory indicators with long-term and 10-year risk of overall and subtype specific lung cancer. Methods and results: This study included 99, 925 participants from the Kailuan cohort (mean follow-up, 14.85 years). During follow-up, 1, 804 incident lung cancer cases were identified. After multivariable adjustment and false discovery rate correction, several inflammatory markers, particularly the novel composite indices SIRI and AISI, were significantly associated with increased overall lung cancer risk. Per 1 Z-score increase, white blood cell count (HR = 1.112, 95% CI: 1.064-1.163), monocytes (HR = 1.060, 95% CI: 1.033-1.087), lymphocytes (HR = 1.050, 95% CI: 1.014-1.087), neutrophils (HR = 1.083, 95% CI: 1.037-1.130), CLR (HR = 1.031, 95% CI: 1.006-1.058), SIRI (HR = 1.536, 95% CI: 1.183-1.995), and AISI (HR = 1.070, 95% CI: 1.023-1.119) showed significant associations. For 10-year risk, similar associations were observed, with SIRI and AISI increasing risk by 75.7% (HR = 1.757, 95% CI: 1.350-2.278) and 9.0% (HR = 1.090, 95% CI: 1.029-1.154), respectively. Subtype analyses revealed significant positive associations for squamous cell carcinoma (e.g., SIRI: HR = 1.782, 95% CI: 1.352-2.350) and other pathological types (e.g., SIRI: HR = 1.638, 95% CI: 1.263-2.125) but not for adenocarcinoma or small cell lung cancer. Stratified analyses showed effect modification by age for SIRI in overall lung cancer (stronger in participants aged ≥60 years), and by sex, age, and smoking status for multiple markers in subtype-specific analyses. SIRI showed the strongest effects across all analyses. Conclusion: Chronic inflammation is differentially associated with lung cancer risk by subtype; SIRI and AISI are independent risk factors, with SIRI showing the strongest effects, particularly for squamous cell carcinoma, in individuals aged ≥ 60 years, and these associations are modified by sex and smoking status.