Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma Journal Article


Authors: Riely, G. J.; Kris, M. G.; Rosenbaum, D.; Marks, J.; Li, A.; Chitale, D. A.; Nafa, K.; Riedel, E. R.; Hsu, M.; Pao, W.; Miller, V. A.; Ladanyi, M.
Article Title: Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma
Abstract: Purpose: KRAS mutations are found in ∼ 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. Experimental Design: 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 smokingrelated (G→Tor 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. © 2008 American Association for Cancer Research.
Keywords: controlled study; oncoprotein; gene mutation; major clinical study; genetics; mutation; proto-oncogene proteins; cigarette smoking; adenocarcinoma; lung neoplasms; genetic association; gene frequency; smoking; lung tumor; lung adenocarcinoma; ras protein; ras proteins; codon; k ras protein; kras protein, human
Journal Title: Clinical Cancer Research
Volume: 14
Issue: 18
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2008-09-15
Start Page: 5731
End Page: 5734
Language: English
DOI: 10.1158/1078-0432.ccr-08-0646
PUBMED: 18794081
PROVIDER: scopus
PMCID: PMC2754127
DOI/URL:
Notes: --- - "Cited By (since 1996): 77" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Allan Rongguo Li
    24 Li
  2. Meier Hsu
    104 Hsu
  3. Khedoudja Nafa
    181 Nafa
  4. William Pao
    141 Pao
  5. Dhananjay Arun Chitale
    33 Chitale
  6. Vincent Miller
    259 Miller
  7. Marc Ladanyi
    861 Ladanyi
  8. Gregory J Riely
    344 Riely
  9. Mark Kris
    597 Kris
  10. Jenifer Lynn Marks
    14 Marks