Molecular Epidemiology of EGFR and KRAS Mutations in 3,026 Lung Adenocarcinomas: Higher Susceptibility of Women to Smoking-Related KRAS-Mutant Cancers

摘要: Purpose: The molecular epidemiology of most EGFR and KRAS mutations in lung cancer remains unclear. Experimental Design: We genotyped 3,026 adenocarcinomas for the major (exon 19 deletions L858R) (G12, G13) examined correlations with demographic, clinical, smoking history data. Results: were found 43% never smokers 11% smokers. occurred 34% 6% In patients histories up to 10 pack-years, predominated over . Among former cancer, multivariate analysis showed that, independent increasing smoking-free years raise likelihood mutation. Never more likely than have G > A transition mutation (mostly G12D; 58% vs. 20%, P = 0.0001). G12C, common T transversion smokers, was frequent women ( 0.007) these younger men same (median 65 69, 0.0008) had smoked less. Conclusions: distinct types versus suggest that -mutant cancers are not due second-hand smoke exposure. higher frequency G12C women, their age, lesser together support a heightened susceptibility tobacco carcinogens. Clin Cancer Res; 18(22); 6169–77. ©2012 AACR