Vital knowledge has been gained from studying driver mutations of cancer, but a few mutations in a limited number of genes cannot fully describe the complexity of carcinogenesis. The recent development of NGS has enabled the identification of genome wide mutational signatures and provided important insights into the underlying causes of human cancer. Although humans mainly are exposed to complex mixtures of agents contributing to cancer development, like air pollution and lung cancer, this research has entirely focused on single mutagens, which likely has impeded the application of mutational signatures in cancer research. The public health impact of understanding these associations is significant; identifying causes of cancer is essential for effective preventative interventions. Here, the aim is to determine mutational signatures of environmental complex mixtures using urban air PM samples and normal lung and liver cells. Mutational signatures will be determined by whole genome sequencing followed by somatic variant-calling, and the air PM samples have been collected in three cities differently impacted by emission sources. The signatures will be functionally validated by transcriptome gene expression analysis and association analyses between enriched pathways and mutational signatures. The proposed project comprises a novel approach by combining advanced NGS technology and environmental samples to establish the mutagenic impact of complex mixtures in cancer development.