4 - Lung Cancer in Never-Smokers: A Different Disease

Abstract

Major clinical, ethnic, gender, and histology differences between lung cancers arising from smokers and never-smokers, coupled with their different etiologic factors and major molecular differences, indicate that they represent different tumor types. Genetic factors play an increasing role in the etiology of lung cancer in never-smokers. These include rare high penetrance mutations in crucial genes such as the T790M mutation in the EGFR gene. The molecular alterations in lung cancers arising in smokers and never-smokers are different, as are the specific mutational targets. KRAS mutations are more frequent in ever-smoker tumors, while EGFR mutations and ALK translocations are more frequent in never-smokers. Ethnic differences between lung cancers arising in ever-smokers and never-smokers point out the importance of genetic susceptibility loci in the development of lung cancers. Lung cancer specialists must recognize that these tumors should be regarded as separate with different pathogeneses and that lung cancers in never-smokers represent a different form of cancer.