Beyond tobacco: understanding the growing burden of lung adenocarcinoma in women
TL;DR
The findings show that estrogen signaling, especially via estrogen receptor beta (ERβ), contributes to oncogenesis, and that incorporating sex-specific risk assessment, hormonal level modification, and targeted gene therapies into clinical practice may improve screening and outcomes for females with lung adenocarcinoma.
Abstract
Primary lung adenocarcinoma is the most common histological subtype of lung cancer. It disproportionately affects female sex, especially never-smokers. The rising incidence among females without a smoking history suggests roles for hormonal, genetic, and environmental factors. We conducted a comprehensive literature review using several databases. We examined global epidemiology data, molecular mechanisms, hormone-related pathways, and new diagnostic and therapeutic approaches. The findings show that estrogen signaling, especially via estrogen receptor beta (ERβ), contributes to oncogenesis. The mechanism involves cross-talk with EGFR and downstream MAPK/PI3K pathways. EGFR mutations appear more frequently in females. The association between KRAS and other cell cycle drivers is mixed across studies. Non-tobacco exposures, including air pollution and secondhand smoke, further increase risk among females. Diagnostic disparities persist because current screening guidelines focus on smoking. This approach excludes many high-risk never-smoking females. This review aims to narrate and synthesize growing evidence highlighting how female sex is associated with a distinct epidemiological footprint, unique molecular and biological profiles, and tailored therapeutic strategies in lung adenocarcinoma, driven by mechanisms beyond traditional tobacco exposure. Incorporating sex-specific risk assessment, hormonal level modification, and targeted gene therapies into clinical practice may improve screening and outcomes for females with lung adenocarcinoma.