Abstract
BACKGROUND: While smoking is the dominant global driver of lung cancer, less than a quarter of Ethiopian patients have ever smoked, pointing to locally relevant risk factors. Evidence to guide prevention and early detection in resource-limited settings is scanty. METHODS: To address this gap, we conducted a multicenter matched case-control study including 351 histopathologically confirmed primary lung cancer cases and 702 hospital-based controls matched by sex, age (±5 years), and residence. Directed acyclic graphs informed the selection of variables, and multivariable hierarchical conditional logistic regression was used to identify risk factors beyond smoking. RESULTS: The analysis shows that lung cancer was independently associated with low education, wealth, solid-fuel use, occupational exposure, insufficient physical activity, meat-based and processed food dietary patterns, secondhand smoke (SHS), prior tuberculosis, and family history of cancer. Subgroup analysis by sex revealed consistent associations across males and females, but exposure distributions explained sex-specific patterns: smoking, occupational exposure, meat-based diets, and family history were more common among males, whereas SHS, the use of solid fuels, and processed food dietary patterns predominated in females. CONCLUSIONS: Lung cancer in Ethiopia appears to be associated with several factors in addition to smoking. Gender-sensitive public health interventions targeting these locally relevant risk factors are essential for effective prevention and early detection.