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Indoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma

Authors
Lim, SM; Choi, JW; Hong, MH; Jung, D; Lee, CY; Park, SY; Shim, HS; Sheen, S; Kwak, KI; Kang, DR; Cho, BC; Kim, HR
Citation
Lung cancer (Amsterdam, Netherlands), 131. : 139-146, 2019
Journal Title
Lung cancer (Amsterdam, Netherlands)
ISSN
0169-50021872-8332
Abstract
OBJECTIVES: Radon, a natural radiation, is the leading environmental cause of lung cancer in never-smokers. However, the radon exposure impact on the mutational landscape and tumor mutation burden (TMB) of lung cancer in never-smokers has not been explored. The aim of this study was to investigate the mutational landscape of lung adenocarcinoma in never-smokers who were exposed to various degrees of residential radon.
MATERIALS AND METHODS: To investigate the effect of indoor radon exposure, we estimated the cumulative exposure to indoor radon in each house of patients with lung cancer with a never-smoking history. Patients with at least 2 year-duration of residence before the diagnosis of lung adenocarcinoma were included. Patients were subgrouped based on the median radon exposure level (48 Bq/m(3)): radon-high vs. radon-low and targeted sequencing of tumor and matched blood were performed in all patients.
RESULTS: Among 41 patients with lung adenocarcinoma, the TMB was significantly higher in the radon-high group than it was in the radon-low group (mean 4.94 vs. 2.6 mutations/Mb, P = 0.01). The recurrence rates between radon-high and radon-low group did not differ significantly. Mutational signatures of radon-high tumors showed features associated with inactivity of the base excision repair and DNA replication machineries. The analysis of tumor evolutionary trajectories also suggested a series of mutagenesis induced by radon exposure. In addition, radon-high tumors revealed a significant protein-protein interaction of genes involved in DNA damage and repair (P < 0.001).
CONCLUSIONS: Indoor radon exposure increased the TMB in never-smoker patients with lung adenocarcinoma and their mutational signature was associated with defective DNA mismatch repair.
Keywords
MutationNon-small-cell lung cancerRadon
MeSH terms
Adenocarcinoma of Lung / genetics*AdultAgedAir Pollutants, Radioactive / adverse effects*Air Pollution, Indoor / adverse effects*Carcinogenesis / geneticsDNA Repair / geneticsDNA Repair / radiation effectsFemaleHumansLung Neoplasms / genetics*MaleMiddle AgedMutagenesis / radiation effectsMutation / genetics*Neoplasm StagingRadiation Exposure / adverse effects*Radon / adverse effects*Transcriptome
DOI
10.1016/j.lungcan.2019.04.002
PMID
31027691
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pulmonary & Critical Care Medicine
AJOU Authors
신, 승수
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