title: Inverse correlation between EGFR mutation and FHIT, RASSF1A and RUNX3 methylation in lung adenocarcinoma: relation with smoking status.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Tobacco smoking is correlated with the frequencies of EGFR and KRAS mutations as to pathogenesis of ACs.
authors.affiliation: Department of Pathology, Yamagata University, Yamagata 990-9585, Japan. nyanagaw@med.id.yamagata-u.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Yanagawa
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oizumi
authors.forename: Makoto
authors.initials: M
authors.lastname: Endoh
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Sadahiro
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D057890:Epigenomics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D050677:Core Binding Factor Alpha 3 Subunit; D004273:DNA, Neoplasm; D066246:ErbB Receptors; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C411762:RASSF1 protein, human; C493729:Runx3 protein, human; C512478:EGFR protein, human