Inverse correlation between EGFR mutation and FHIT, RASSF1A and RUNX3 methylation in lung adenocarcinoma: relation with smoking status.

BACKGROUND Epidemiological studies have demonstrated a causal link between tobacco smoking and lung cancer. However, lung adenocarcinoma (AC) is also frequently found in non-smokers compared with other non-small cell lung carcinoma (NSCLC) subtypes. MATERIALS AND METHODS Mutations of both epithelial growth factor receptor (EGFR) and KRAS, and the methylation status of 10 tumor suppressor or tumor-related genes were examined in 62 ACs, and the relationship with smoking status, and the relationship between the genetic alterations and epigenetic alterations were investigated. RESULTS The frequency of EGFR mutation was strongly correlated with smoking status, and the frequency of KRAS mutation, and methylation of retinoic acid receptor beta (RAR-β), p16, FHIT and RASSF1A were weakly related with smoking status. Inverse correlation was found between EGFR mutation and FHIT, RASSF1A and RUNX3 methylation. CONCLUSION Tobacco smoking is correlated with the frequencies of EGFR and KRAS mutations as to pathogenesis of ACs.