title: The impact of cigarette smoking on the frequency of and qualitative differences in KRAS mutations in Korean patients with lung adenocarcinoma.
abstract: OBJECTIVE
  This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients.
  
  
  METHODS
  Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing.
  
  
  RESULTS
  The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G→A or C→T) rather than a transversion mutation (G→T or G→C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation.
  
  
  CONCLUSIONS
  Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.
authors.affiliation: Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.forename: Jung Ryun
authors.initials: JR
authors.lastname: Ahn
authors.forename: Jin Gu
authors.initials: JG
authors.lastname: Lee
authors.forename: Doo Hee
authors.initials: DH
authors.lastname: Bang
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.forename: Yun Kyoung
authors.initials: YK
authors.lastname: Hong
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Ki Chang
authors.initials: KC
authors.lastname: Nam
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Ross A
authors.initials: RA
authors.lastname: Soo
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.forename: Joo Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: EGFR; EGFR-tyrosine kinase inhibitors; KRAS; cigarette smoking; pulmonary adenocarcinoma