Association of childhood maltreatment with risk of lung cancer: A mediation analysis from the UK biobank.
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BACKGROUND: Childhood maltreatment (CM) has been associated with a higher risk of developing cancer later in life. However, the association between CM and lung cancer has not been thoroughly validated, and a comprehensive assessment of the mechanistic pathways underlying this relationship remains unaddressed. OBJECTIVE: This study aims to prospectively investigate the impact of CM and its specific subtypes on the risk of incident lung cancer in adulthood, and to explore the mediating effects of unfavorable lifestyles, psychological adversity, and biological alterations. METHODS: We included 117,281 participants enrolled in the UK Biobank between 2006 and 2010, who were followed up until June 1, 2022. CM was retrospectively assessed in 2016 using the online Childhood Trauma Screener. Cox proportional hazard models were employed to examine the association between CM and lung cancer. Mediation analysis was performed to estimate the mediating effects of potential mediators. RESULTS: Over a median follow-up period of 13.46 years, 414 participants were diagnosed with lung cancer. CM was associated with a greater risk of lung cancer. Each additional type of CM corresponding to an 11% higher risk (hazard ratio [HR], 1.11 [95% CI, 1.02-1.20]). The presence of physical abuse (HR, 1.42 [95% CI, 1.12-1.78]) and emotional abuse (HR, 1.33 [95% CI, 1.03-1.71]) was associated with an increased risk of lung cancer, respectively. Mediation analyses indicated that the observed association was largely mediated by smoking status (41.39%), self-rated mental problem (23.26%), and CRP-to-albumin ratio (6.64%). CONCLUSIONS: CM experiences are associated with higher risk of developing lung cancer in later life. Furthermore, smoking and self-rated mental problem constitute the main pathways in this relationship. These findings not only suggest the potential clinical value of incorporating childhood maltreatment assessments into future precision screening models, but also underscore the necessity of deeply integrating mental health support with traditional smoking cessation interventions for this vulnerable demographic. Fundamentally, preventing the occurrence of maltreatment during childhood can effectively mitigate the subsequent risk of lung cancer incidence.