Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development

Lung Cancer. 2012 Feb;75(2):156-60. doi: 10.1016/j.lungcan.2011.07.013. Epub 2011 Aug 11.


Background: In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis.

Methods: A nested case-study was performed on 233 non-small cell lung carcinomas. Cases were selected on the basis of progressive disease or disease-free post surgery based on specific criteria. KRAS mutation analysis was performed with the point-EXACCT method.

Results: KRAS mutations were found in 39 adenocarcinomas and 1 squamous cell carcinoma in the 233 NSCLC. The median quitting smoking time (QST) for patients with and without KRAS mutations was 9 years, interquartile range [IQR 16-38] and 3 years, IQR [13-50], respectively (p=0.039). No difference was found for age at initiation of smoking, duration of smoking, average tobacco consumption, and smoking status at the time of diagnosis.

Conclusion: The QST was longer for patients with KRAS mutations, supporting the notion that the presence of a KRAS mutation is a dominant early effect, supporting its role as a driver oncogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Humans
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Mutation*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Smoking / adverse effects*
  • Smoking Cessation
  • Time Factors
  • ras Proteins / genetics*


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins