Lung cancer is a multifactorial disease driven by environmental exposures, especially cigarette smoking, inherited germline genetic variants and an accumulation of somatic genetic events. Lung cancer genes are reported in a new article in Nature Genetics. Researchers found new links between genes and lung cancer.
Lung cancer genes were identified by a large-scale meta-analysis
To identify links between genes and lung cancer among diverse populations, the researchers performed cross-ancestry genome-wide association studies in European, East Asian, and African populations. The research team analyzed data from more than 61,000 lung cancer patients and nearly 1 million study controls.
They discovered five new susceptibility loci that have not been previously reported and 10 new variant associations from known risk genes. The team also further validated another 24 associations in different populations. They reported that rare-variant associations tended to be specific to populations. Even some commonly known risk factors showed population specificity.
They found that susceptibility candidate genes were frequently linked to biological pathways involving immune and cellular stress response. The researchers also performed functional assays on the susceptibility genes in lung fibroblast cells and found that many of these genes promote DNA damage.
This study can help with identification of people who are at highest risk for developing lung cancer. Knowing the risk can help people change their behaviors to reduce the possibility of developing lung cancer. The genes that promote DNA damage may be good therapeutic targets. The results of this study may help in the developing of more precise personalized therapy of lung cancer.
Quantifying the genomic architecture of lung cancer risk is important to better understanding its pathogenesis. Therefore, improved elucidation of genetics in lung carcinogenesis is critical. For instance, better understanding the genomic diversity of oncogenes, tumor suppressor genes or specific alterations across diverse ancestry populations can help in designing population-specific targeted therapies.
Reference: Byun, J. et al. Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer. Nat Genet (2022). https://doi.org/10.1038/s41588-022-01115-x
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