J Korean Med Sci.  2018 Jul;33(29):e207. 10.3346/jkms.2018.33.e207.

Radon Exposure-induced Genetic Variations in Lung Cancers among Never Smokers

• Choi JR
• Koh SB
• Kim HR
• Lee H
• Kang DR

• KMID: 2416148
• DOI: http://doi.org/10.3346/jkms.2018.33.e207

Abstract

BACKGROUND
Lung cancer in never smokers (LCINS) differs etiologically and clinically from lung cancer attributed to smoking. After smoking, radon exposure is the second leading cause and the primary risk factor of lung cancer among never smokers. Exposure to radon can lead to genetic and epigenetic alterations in tumor genomes affecting genes and pathways involved in lung cancer development. The present study sought to explore genetic alterations associated with LCINS exposed to radon gas indoors.
METHODS
Genetic associations were assessed via a case-control study of LCINS (39 cases and 30 controls) using next generation sequencing. Associations between genetic mutations and high exposure to radon were investigated by OncoPrint and heatmap graphs. Bioinformatic analysis was conducted using various tools. According radon exposure levels, we divided subjects in two groups of cases and controls.
RESULTS
We found that ABL2 rs117218074, SMARCA4 rs2288845, PIK3R2 rs142933317, MAPK1 rs1803545, and androgen receptor (AR) rs66766400 were associated with LCINS exposed to high radon levels. Among these, Chromodomain helicase DNA-binding protein 4 (CHD4) rs74790047, TSC2 rs2121870, and AR rs66766408 were identified as common exonic mutations in both lung cancer patients and normal individuals exposed to high levels of radon indoor.
CONCLUSION
We identified that CHD4 rs74790047, TSC2 rs2121870, and AR rs66766408 are found to be common exonic mutations in both lung cancer patients and normal individuals exposed to radon indoors. Further analysis is needed to determine whether these genes are completely responsible for LCINS exposed to residential radon.

Keyword

Lung Cancer in Never Smokers; Radon Exposure; Genetic Alteration; Next Generation Sequencing

MeSH Terms

Case-Control Studies
Computational Biology
Epigenomics
Exons
Genetic Variation*
Genome
Humans
Lung Neoplasms*
Lung*
Radon*
Receptors, Androgen
Risk Factors
Smoke
Smoking
Radon
Receptors, Androgen
Smoke