Is residential radon associated with mutations in drivers genes in never smokers lung cancer cases? The case of EGFR and ALK

Objetive: Lung cancer in never smokers has different molecular pathways than lung cancer occurring in ever-smokers, including driver mutations/alterations in genes EGFR and ALK. Residential radon is the first risk factor in never smokers. There are no studies analyzing if residential radon is related with driver mutations in both genes. We aimed to analyze if residential radon concentrations were different in individuals having EGFR or ALK alterations. Methods: We performed a multicentre case-control study including exclusively never smokers. All patients had confirmed lung cancer diagnosis and radon detectors were placed at their homes. We retrieved clinical information from participants. We compared median values of residential radon between patients with EGFR or ALK positive versus those negative. Results: We recruited 323 patients, 209 were included in the genetic analysis (64.7%). Median age: 70, 19.5% males. 42% and 15% of patients were positive for EGFR and ALK, respectively. The most frequent alterations for EGFR were exon 19 deletions and L858R mutations. ALK positive patients were 10 years younger than ALK negative. Residential radon was twofold in patients with exon 19 deletion compared with patients with L858R mutation (216 vs 118 Bq/m3; p = 0.057). No differences between negative and positive EGFR patients regarding residential radon. ALK positive patients (n=11) had higher residential radon compared with negative patients, though differences were not significant (290 vs 164 Bq/m3, respectively). Conclusions: These results provide a plausible and alternative explanation to alterations found in driver genes in never smoking lung cancer patients.