K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos

Int J Cancer. 1993 Jan 21;53(2):250-6. doi: 10.1002/ijc.2910530213.


We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed--in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation--a clear association of K-ras mutations with heavy life-time smoking (> or = 50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2-19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6-8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adult
  • Aged
  • Asbestos / adverse effects*
  • Base Sequence
  • Female
  • Genes, ras / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Occupational Exposure / adverse effects
  • Point Mutation*
  • Polymerase Chain Reaction
  • Smoking / genetics*


  • Asbestos