Abstract Background: The Advanced Lung Cancer Inflammation Index (ALI)—a composite of BMI, albumin, and neutrophil-to-lymphocyte ratio—is a validated prognostic marker in lung cancer. However, its potential as a pre-diagnostic biomarker for systemic inflammation remains underexplored, especially in the context of behavioral risk factors and sociodemographic disparities. We aimed to identify predictors of high-risk ALI in cancer-free young adults in the United States. Methods: We used NHANES 2015–2018 data and included adults aged 20–50 years without a history of lung cancer and with complete ALI components (n=4,830). High-risk ALI was defined as the lowest tertile of the ALI distribution. The primary exposure was current cigarette and/or e-cigarette use. Survey-weighted logistic regression was used to estimate adjusted odds ratios (aORs) for high-risk ALI, adjusting for sociodemographic variables, comorbidities, physical activity, alcohol use, and insurance status. Results: Overall, 34.7% of participants had high-risk ALI. Exclusive cigarette smoking was significantly associated with high-risk ALI (aOR 1.55; 95% CI: 1.29–1.88; p0.0001). E-cigarette use alone or dual use was not significant. Other predictors of high-risk ALI included female sex (aOR 1.86), U.S. birth (aOR 1.29), and heavy alcohol use (aOR 1.56). Compared to White, non-Hispanic participants, Black, non-Hispanic individuals had lower odds (aOR 0.40). Higher education was protective (aOR 0.73). Conclusion: In cancer-free adults, ALI may reflect early, biologically plausible immune-metabolic stress linked to tobacco exposure and socially patterned health risks. These findings underscore the potential of ALI as a pre-diagnostic biomarker in population-level surveillance. Our results emphasize the need for longitudinal validation and prevention strategies targeting systemic inflammation in vulnerable groups. Citation Format: Nehemias A. Guevara Rodriguez, Noemy E. Coreas, Syeda Ashna. Fatima Kamal, Sumrah Khan, Brian Abboud, Joanne Salas, Asha Ricciuti. Systemic inflammation before diagnosis: Smoking, disparities, and ALI in cancer-free young adults — a nationwide signal of lung cancer risk? abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B132.
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Nehemias Antonio Guevara Rodriguez
Saint Louis University
Noemy Coreas
University of El Salvador
Syeda Ashna Fatima Kamal
Saint Louis University Hospital
Cancer Epidemiology Biomarkers & Prevention
Saint Louis University
University of El Salvador
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Rodriguez et al. (Thu,) studied this question.
synapsesocial.com/papers/68d464f131b076d99fa64441 — DOI: https://doi.org/10.1158/1538-7755.disp25-b132