[China Wumeng Mountain Lung Cancer: Evidence Chain, Clinical and Molecular Characteristics of Regional Lung Cancer Related to Coal Pollution in the Yunnan-Guizhou Plateau].

Abstract

Background: Long-term household coal burning, differences in coal sources and mineral compositions, energy structure, and socioeconomic conditions jointly constitute the regional exposure basis for lung cancer. This study conducts a multi-sectional, multi-dimensional and multi-omics investigation on the correlation between coal-burning pollution in the "Wumeng Mountain region" and "China Wumeng Mountain lung cancer", and explores the concept boundaries, evidence chain, carcinogenic components, clinical and molecular characteristics, as well as the precise prevention and control pathways of "China Wumeng Mountain lung cancer", with the aim of providing evidences and references for the primary, secondary, tertiary and quaternary prevention of lung cancer in high-incidence areas of "China Wumeng Mountain lung cancer", as well as the screening and molecular typing management of high-risk populations.

Methods: Based on the relatively complete evidence chain established in our previous research, covering household coal smoke exposure, coal source differences, polycyclic aromatic hydrocarbons (PAHs), stove intervention, lung cancer and tumor multi-omics characteristics, a narrative review method was applied for literature search and evidence integration. The search databases included PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang Database, with the time range from the establishment of each database to May 2026; search terms included: Xuanwei, Fuyuan, Wumeng Mountains, household coal combustion, smoky coal, lung cancer, PAHs, methylated PAHs, stove improvement, never-smoking women, germline susceptibility, microbiome and multi-omics. The evidence integration adopted the "exposure-pollutant component-biological effect-clinical molecular characteristics-prevention transformation" evidence chain.

Results: (1) PAHs/methylated PAHs, particulate matter 2.5 (PM2.5)/black carbon, inorganic minerals/metals, carbonyl compounds and mixed exposure are the main carcinogenic components of coal-burning pollution-related lung cancer; (2) It is prevalent among non-smoking women, with a high proportion of adenocarcinoma, low age of onset, easy early metastasis, multiple lung lesions and family aggregation are the clinical characteristics of coal-burning pollution-related lung cancer in the Wumeng Mountain region; (3) The total epidermal growth factor receptor (EGFR) mutation is relatively high, but the proportions of classic EGFR 19 exon deletion and L858R mutation are relatively low, while EGFR-G719X, S768I mutations, Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations, and anaplastic lymphoma kinase (ALK) and c-ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene fusion mutations are significantly higher than those in non-Wumeng Mountain lung cancer; (4) Germline mutation genes ARHGEF5, MYO18B and MUC16 are potential genetic susceptibility genes for coal-burning pollution-related lung cancer in the Wumeng Mountain region, and they interact with telomere length maintenance genes POT1, TERT and TERF2, and may have a close relationship with the existence of lung cancer family aggregation in this region; (5) Indoor coal-burning pollution leads to changes in the microbial community of sputum, and long-term chronic infection of the respiratory tract jointly affect abnormal pathways related to the immune microenvironment and pollutant metabolism, increasing the risk of lung cancer.

Conclusions: China Wumeng Mountain lung cancer is a type of lung cancer related to indoor and outdoor coal-burning pollution, with a predilection for never-smoking women, high proportion of adenocarcinoma, low age of onset, multiple lung lesions, as well as special chronic respiratory infections, abnormal pollutant metabolism and immune microenvironment, as well as special driver gene and germline mutation gene mutation spectra.