Abstract LB231: The mutagenic forces shaping the genomic landscape of lung cancer in never smokers
Abstract
While most lung cancers are associated with tobacco smoking, prior studies have indicated that 15-20% of cases are found in never smokers. Lung cancer in never smokers (LCINS) shows demographic variations, being more common in females and Asian populations. Epidemiological studies have also identified environmental risk factors for LCINS, including exposure to secondhand tobacco smoke and air pollution. As part of the Sherlock-Lung project (current data freeze of 1217 samples), we generated deep WGS data from a large international cohort of 871 treatment-naïve LCINS recruited from 28 locations across four continents. Our cohort allowed mapping the genomic landscape operative in lung cancer histologies commonly found in never smokers, including adenocarcinomas (n=737) and carcinoids (n=61), as well as other histologies rarely attributed to never smokers (n=73). Information on passive smoking was collected for 458 patients, with 250 being exposed to secondhand smoke. We identified driver alterations and performed mutational signature analyses for single base substitutions (SBS), indels, doublet base substitutions (DBS), copy number alterations, and structural variants.
We detected eighteen SBS signatures, with eight not previously linked to LCINS, including SBS4, associated with smoking but also observed in lifelong non-smokers exposed to different environmental mutagens, such as indoor pollution. Several additional signatures were detected in other variant types, including a…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 737 participants or records.
Read the paper
Related studies
- Tobacco and COPD: presenting the World Health Organization (WHO) Tobacco Knowledge Summary
- Comparative effects of e-cigarette smoking on periodontal status, salivary pH, and cotinine levels
- Association between exposure to environmental pollutants and increased oral health risks, a comprehensive review
- Influence of gestational window on offspring vascular health in rodents with in utero exposure to electronic cigarettes
- Natural products as kinase inhibitors in lung cancer: molecular mechanisms, therapeutic potential, and clinical trials
- Nicotine in electronic cigarettes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.