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

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dc.contributor.authorLim, SM-
dc.contributor.authorChoi, JW-
dc.contributor.authorHong, MH-
dc.contributor.authorJung, D-
dc.contributor.authorLee, CY-
dc.contributor.authorPark, SY-
dc.contributor.authorShim, HS-
dc.contributor.authorSheen, S-
dc.contributor.authorKwak, KI-
dc.contributor.authorKang, DR-
dc.contributor.authorCho, BC-
dc.contributor.authorKim, HR-
dc.date.accessioned2020-11-17T05:32:58Z-
dc.date.available2020-11-17T05:32:58Z-
dc.date.issued2019-
dc.identifier.issn0169-5002-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/19110-
dc.description.abstractOBJECTIVES: 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.
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dc.language.isoen-
dc.subject.MESHAdenocarcinoma of Lung-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAir Pollutants, Radioactive-
dc.subject.MESHAir Pollution, Indoor-
dc.subject.MESHCarcinogenesis-
dc.subject.MESHDNA Repair-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHLung Neoplasms-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutagenesis-
dc.subject.MESHMutation-
dc.subject.MESHNeoplasm Staging-
dc.subject.MESHRadiation Exposure-
dc.subject.MESHRadon-
dc.subject.MESHTranscriptome-
dc.titleIndoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma-
dc.typeArticle-
dc.identifier.pmid31027691-
dc.subject.keywordMutation-
dc.subject.keywordNon-small-cell lung cancer-
dc.subject.keywordRadon-
dc.contributor.affiliatedAuthor신, 승수-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.lungcan.2019.04.002-
dc.citation.titleLung cancer (Amsterdam, Netherlands)-
dc.citation.volume131-
dc.citation.date2019-
dc.citation.startPage139-
dc.citation.endPage146-
dc.identifier.bibliographicCitationLung cancer (Amsterdam, Netherlands), 131. : 139-146, 2019-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1872-8332-
dc.relation.journalidJ001695002-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pulmonary & Critical Care Medicine
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