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

 Sun Min Lim  ;  Jae Woo Choi  ;  Min Hee Hong  ;  Dongmin Jung  ;  Chang Young Lee  ;  Seong Yong Park  ;  Hyo Sup Shim  ;  Seungsoo Sheen  ;  Kyeong Im Kwak  ;  Dae Ryong Kang  ;  Byoung Chul Cho  ;  Hye Ryun Kim 
 LUNG CANCER, Vol.131 : 139-146, 2019 
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Issue Date
Mutation ; Non-small-cell lung cancer ;  Radon
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/m3): 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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Seong Yong(박성용)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Chang Young(이창영)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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