title: Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma.
abstract: OBJECTIVE
  KRAS mutations are found in approximately 25% of lung adenocarcinomas in Western countries and, as a group, have been strongly associated with cigarette smoking. These mutations are predictive of poor prognosis in resected disease as well as resistance to treatment with erlotinib or gefitinib.
  
  
  METHODS
  We determined the frequency and type of KRAS codon 12 and 13 mutations and characterized their association with cigarette smoking history in patients with lung adenocarcinomas.
  
  
  RESULTS
  KRAS mutational analysis was done on 482 lung adenocarcinomas, 81 (17%) of which were obtained from patients who had never smoked cigarettes. KRAS mutations were found in 15% (12 of 81; 95% confidence intervals, 8-24%) of tumors from never smokers. Similarly, 22% (69 of 316; 95% confidence intervals, 17-27%) of tumors from former smokers, and 25% (21 of 85; 95% confidence intervals, 16-35%) of tumors from current smokers had KRAS mutations. The frequency of KRAS mutation was not associated with age, gender, or smoking history. The number of pack years of cigarette smoking did not predict an increased likelihood of KRAS mutations. Never smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A) rather than the transversion mutations known to be smoking-related (G-->T or G-->C; P < 0.0001).
  
  
  CONCLUSIONS
  Based on our data, KRAS mutations are not rare among never smokers with lung adenocarcinoma and such patients have a distinct KRAS mutation profile. The etiologic and biological heterogeneity of KRAS mutant lung adenocarcinomas is worthy of further study.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. rielyg@mskcc.org
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosenbaum
authors.forename: Jenifer
authors.initials: J
authors.lastname: Marks
authors.forename: Allan
authors.initials: A
authors.lastname: Li
authors.forename: Dhananjay A
authors.initials: DA
authors.lastname: Chitale
authors.forename: Khedoudja
authors.initials: K
authors.lastname: Nafa
authors.forename: Elyn R
authors.initials: ER
authors.lastname: Riedel
authors.forename: Meier
authors.initials: M
authors.lastname: Hsu
authors.forename: William
authors.initials: W
authors.lastname: Pao
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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