Research advances on molecular mechanisms of lung cancer regulated by environmental factors via DNA methylation and clinical translation
- VernacularTitle:环境因素通过DNA甲基化调控肺癌的分子机制及临床转化研究进展
- Author:
Zhimin XIAO
1
;
Yan GU
1
Author Information
- Publication Type:Review
- Keywords: environmental exposure; DNA methylation; lung cancer epigenetic marker; DNA methyltransferase inhibitor; multi-omics integration; clinical translation
- From: Journal of Environmental and Occupational Medicine 2025;42(12):1536-1545
- CountryChina
- Language:Chinese
- Abstract: Environmental factors play a pivotal role in the pathogenesis and progression of lung cancer, with epigenetic regulation, particularly DNA methylation, serving as a central molecular mechanism. This review systematically elaborated on the mechanisms by which environmental exposures dynamically regulate lung cancer development through influencing DNA methylation and summarized recent advances in the clinical translation of related epigenetic biomarkers for early diagnosis and targeted therapy. Relevant studies published between December 2018 and March 2025 were retrieved from Chinese and English databases, and 64 articles were included in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Environmental exposures can specifically induce abnormal methylation of tumor suppressor genes such as the aryl hydrocarbon receptor repressor (AHRR) and Ras‑associated domain family 1 isoform A (RASSF1A), thereby promoting genomic instability and activation of oncogenes. In terms of clinical translation, methylation detection of genes including short stature homeobox 2 (SHOX2) and RASSF1A in plasma has demonstrated favorable diagnostic performance, with a sensitivity of 87.0% (95%CI: 80.2%, 91.5%) and a specificity of 98.0% (95%CI: 94.9%, 99.4%), indicating its applicability for early screening of lung cancer. However, although current DNA methyltransferase (DNMT) inhibitors can achieve epigenetic reprogramming, their applications still face challenges related to insufficient selectivity among different tumor subtypes. Given that environmental factors drive lung carcinogenesis via epigenetic mechanisms, there is an urgent need to establish a three‑tier prevention and control framework encompassing “environmental monitoring – methylation biomarker screening – targeted intervention.” Future efforts should focus on deepening integrated multi‑omics analyses, developing subtype‑selective DNMT inhibitors, and optimizing multimodal detection strategies for methylation biomarkers to advance precision prevention and treatment of lung cancer.
