Etiology and risk factors for lung cancer in female Asian never smokers: a systematic review

Background Lung cancer remains the leading cause of cancer-related mortality worldwide, with a growing proportion of cases occurring in female Asian never-smokers (FANS). Although tobacco exposure remains the predominant risk factor, emerging evidence highlights the substantial role of non-tobacco determinants. However, the relative contributions of these factors remain poorly defined. Objectives This systematic review aimed to synthesize existing evidence on biological, clinical, and environmental risk factors for lung cancer among FANS to identify consistent and potentially modifiable exposures to inform risk-stratified prevention strategies. Genetic and molecular determinants were excluded. Design Systematic review. Data sources and methods Following PRISMA-P guidelines, we systematically searched PubMed, Embase, CINAHL, and Web of Science for articles published between January 2000 and July 2025 to identify peer-reviewed observational studies reporting non-tobacco risk factors for lung cancer in FANS. Due to the heterogeneity in study designs, a narrative synthesis was performed on the final 42 studies. Results Indoor air pollution, such as high-temperature cooking oil fumes, prolonged solid-fuel use, and inadequate household or workplace ventilation, consistently conferred elevated risks (2-4× higher). Risk estimates increased up to 12-fold for high cumulative exposures. This risk was also seen in occupational exposures such as commercial cooking and International Agency for Research on Cancer-classified industrial jobs. Family history of lung cancer, especially among first-degree relatives, nearly doubled risk in several large cohorts. Prior non-malignant lung diseases such as tuberculosis, asthma, and lymphangioleiomyomatosis were also significantly associated with increased risk. Conclusion Lung cancer in FANS may be driven by largely modifiable non-tobacco exposures. These findings underscore the need to expand risk assessments beyond smoking history to incorporate detailed household, occupational, and clinical exposures, and to develop targeted, culturally informed prevention and screening strategies for this high-risk population. Trial registration The protocol was registered in PROSPERO (CRD420251111993).