Association between environmental tobacco smoke exposure and the occurrence of EGFR mutations and ALK -rearrangements in never-smokers with non-small cell lung cancer: analyses from a prospective multinational ETS registry

• Published in: Clinical lung cancer 2017-09, Vol.18 (5), p.535-542
• Main Authors: Soo, Ross A., MD, Kubo, Akihito, MD PhD, Ando, Masahiko, MD PhD, Kawaguchi, Tomoya, MD PhD, Ahn, Myung-Ju, MD PhD, Ou, Sai-Hong Ignatius, MD PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; ALK gene rearrangements; Carcinoma, Non-Small-Cell Lung - genetics; EGFR mutations; Female; Gene Rearrangement; Hematology, Oncology and Palliative Medicine; Humans; Internationality; Japan; Lung cancer; Lung Neoplasms - genetics; Male; Middle Aged; Mutation; Never smoker; Passive smoking; Prospective Studies; Pulmonary/Respiratory; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Epidermal Growth Factor - genetics; Registries; Republic of Korea; Sex Factors; Singapore; Tobacco Smoke Pollution - adverse effects; Tobacco Smoke Pollution - statistics & numerical data; United States
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2017.01.005

Abstract Background Molecular studies have demonstrated actionable driver oncogene alterations are more frequent in never-smokers with non-small cell lung cancer (NSCLC). The etiology of these driver oncogenes in NSCLC patients remains unknown and environmental tobacco smoke (ETS) is a potential cause in these cases. Materials and methods We assembled clinical and genetic information for never-smoker NSCLC patients accrued in Japan, Korea, Singapore, and the US. To determine an association between cumulative ETS and activating EGFR mutations or ALK rearrangements, the Mantel extension test was used. Multivariate analysis on activating EGFR and ALK gene rearrangements was performed using the generalized linear mixed model with nations as a random effect. Results From July 2007 and December 2012, 498 never-smokers with pathologically proven NSCLC were registered and tested for the association between ETS and EGFR and ALK status. EGFR mutations were more frequent in ever ETS cohort (58.4%) compared with never ETS cohort (39.6%) and the incidence of EGFR mutations was significantly associated with the increment of cumulative ETS (cETS) in female never-smokers (P = 0.033), whereas the incidence of ALK rearrangements was not significantly different between ever ETS and never ETS cohort. Odds ratio for EGFR mutations for each 10 year increment in cETS was 1.091 and 0.89 for female and male never-smokers (p=0.031 and 0.263, respectively). Conclusion Increased ETS exposure was closely associated with EGFR mutations in female never-smokers with NSCLC in the expanded multinational cohort. However, the association of ETS and ALK rearrangements in never-smokers with NSCLC was not significant.