Impact of environmental tobacco smoke (ETS) on ALK rearrangements in never smokers (NS) with non-small cell lung cancer (NSCLC): Analyses on a prospective multinational ETS registry.

Abstract

7565 Background: EGFR and ALK are important driver mutations in NS. While we reported the significant association of increased ETS with EGFR mutations in Japanese cohort (Kawaguchi, Clin Cancer Res, 2011), ETS association with ALK has not been reported. Methods: ETS exposure on NS with NSCLC was evaluated using the standardized questionnaire including exposure period, place, and duration. Cumulative dose of ETS (CETS) was defined as a sum of the number of the exposure years in childhood and in adulthood, and was treated as a continuous variable or quintile. EGFR mutations and ALK rearrangements were tested by PCR-based detection and fluorescence in situ hybridization, respectively. Multivariate analyses were done using the generalized linear mixed model (GLIMMIX procedure, SAS v9.3). Results: From March 2008 to December 2012, 498 NS with NSCLC were registered with the following patient characteristics: ethnicity (nationality) of Asian/ Caucasian/ others, 425 (Japanese 250, Korean 102, Chinese 46, others 2)/ 48/ 25; male/female, 114/384; age <65/>=65, 286/212. EGFR status was wild type 43.6%, exon 19 deletion 25.3%, L858R 21.5% and other mutations 9.6%. ALK status was wild type 52.0%, rearranged 10.6% and unknown 37.3%. Average CETS (years) of NS with EGFR (+), ALK (+) and wild type tumors were 45.4, 26.9 and 37.7, respectively. In multivariate generalized linear mixed model, incidence of activating EGFR mutations, not ALK rearrangements, was significantly associated with the increment of CETS in female, not in male gender. Odds ratios (OR) for EGFR mutations in female (n=384) were 1.084 (95% CI, 1.003-1.171; p=0.0422) for each increment of 10 years in CETS while OR in male (n=114) were not significant (OR 0.890; 95% CI, 0.725-1.093; p=0.2627). OR for ALK rearrangements in female (n=238) and those in male gender (n=74) were 0.930 (0.791-1.094; p=0.3814) and 0.854 (0.620-1.178; p=0.3319). Conclusions: Increased ETS exposure was closely associated with EGFR mutations in NS with female gender and NSCLC in the expanded multinational cohort. However, the association of ETS and ALK rearrangements in NS with NSCLC was not significant.