Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: Higher susceptibility of women to smoking-related KRAS-mutant cancers Journal Article


Authors: Dogan, S.; Shen, R.; Ang, D. C.; Johnson, M. L.; D'Angelo, S. P.; Paik, P. K.; Brzostowski, E. B.; Riely, G. J.; Kris, M. G.; Zakowski, M. F.; Ladanyi, M.
Article Title: Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: Higher susceptibility of women to smoking-related KRAS-mutant cancers
Abstract: Purpose: The molecular epidemiology of most EGFR and KRAS mutations in lung cancer remains unclear. Experimental Design: We genotyped 3,026 lung adenocarcinomas for the major EGFR (exon 19 deletions and L858R) and KRAS (G12, G13) mutations and examined correlations with demographic, clinical, and smoking history data. Results: EGFR mutations were found in 43% of never smokers and in 11% of smokers. KRAS mutations occurred in 34% of smokers and in 6% of never smokers. In patients with smoking histories up to 10 packyears, EGFR predominated over KRAS. Among former smokers with lung cancer, multivariate analysis showed that, independent of pack-years, increasing smoking-free years raise the likelihood of EGFR mutation. Never smokers were more likely than smokers to have KRAS G > A transition mutation (mostly G12D; 58% vs. 20%, P = 0.0001). KRAS G12C, the most common G > T transversion mutation in smokers, was more frequent in women (P=0.007) and these women were younger thanmen with the same mutation (median 65 vs. 69, P = 0.0008) and had smoked less. Conclusions: The distinct types of KRAS mutations in smokers versus never smokers suggest that most KRAS-mutant lung cancers in never smokers are not due to second-hand smoke exposure. The higher frequency of KRAS G12C in women, their younger age, and lesser smoking history together support a heightened susceptibility to tobacco carcinogens. ©2012 AACR.
Journal Title: Clinical Cancer Research
Volume: 18
Issue: 22
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2012-11-15
Start Page: 6169
End Page: 6177
Language: English
DOI: 10.1158/1078-0432.ccr-11-3265
PROVIDER: scopus
PMCID: PMC3500422
PUBMED: 23014527
DOI/URL:
Notes: --- - "Export Date: 3 December 2012" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Ronglai Shen
    127 Shen
  2. Melissa Lynne Johnson
    19 Johnson
  3. Marc Ladanyi
    863 Ladanyi
  4. Daphne Chua Ang
    14 Ang
  5. Gregory J Riely
    344 Riely
  6. Maureen F Zakowski
    275 Zakowski
  7. Paul K Paik
    88 Paik
  8. Snjezana Dogan
    86 Dogan
  9. Mark Kris
    597 Kris