Identifying chemicals linked to lung cancer: Integrating genome-wide association studies with a chemical-gene interaction network

Abstract Background Lung cancer is the most common cancer and the leading cause of cancer-related mortality worldwide. Environmental chemicals play a significant role in tumorigenesis, it is necessary to explore the lung cancer-related chemicals and provide new clues for neoplastic prevention and treatment. Methods The genome-wide association study (GWAS) summary data of malignant neoplasm of bronchus and lung (C34) were downloaded from the UK Biobank. It includes 1,655 samples and 450,609 controls. DNA methylation profiles of non-small cell lung cancer were obtained from the GEO database (GSE75008). A transcriptome-wide association study was applied to detect genes significantly related to lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) by FUSION software. Comparative toxicogenomics database (CTD) enables the construction of chemical-gene-disease networks. We conducted a chemical-related gene set enrichment analysis (GSEA) based on GWAS summary data, DNA methylation data, and the CTD to explore the relationships between chemicals and two major histological subtypes of lung cancer. Venn analysis was used to identify the common related chemicals of the GWAS summary data and the DNA methylation data. Results We detected aluminum, naringenin, and 2-acetylaminofluorene as LUSC-related chemicals and antirheumatic agents, nickel monoxide, and 2-amino-2-methyl-1-propanol as LUAD-related chemicals. Conclusion By integrating GWAS and chemical-gene interaction networks, we made linkages between various chemicals and lung cancer on genetic basis. Moreover, this study provided new clues for exploring the etiology of lung cancer and a new method for finding the chemicals related to tumor or other complex disease.