Never smokers who develop lung cancer have different types of tumors than those that form in smokers.
Principal investigator, Kelsie Thu, from the British Columbia Cancer Agency Research Centre in Vancouver, Canada, found many differences in the alteration of genes in smoker's lung cancer and non-smoker's lung cancers. In non-smokers, a larger percentage of lung tumor DNA contained genetic alterations compared to smokers.
This discovery suggests that lung cancers in these two groups are very likely distinct diseases driven by different molecular mechanisms, and thus, may require different treatments.
Interestingly, almost 25 percent of lung cancer cases worldwide occur in people who have never smoked, and they typically exhibit traits different from those of smokers. This group of patients are more often Asian, female, have a higher incidence of epidermal growth factor receptor (EGFR) mutations, respond better to EGFR-targeting drugs and are more commonly diagnosed with adenocarcinoma, which is a highly treatable type of lung cancer found mostly in women.
Thu observes that prior to this study there were few known differences between lung cancers in smokers and non-smokers. This research has shown that the differences are genetic. Genome-wide patterns in lung cancer differ between the two groups.
Thu predicts that the genetic alterations specific to never-smokers may play an important role in the development of their lung cancer.
Researchers obtained DNA from lung adenocarcinomas and matched non-malignant tissues for 30 never-smokers, 14 former smokers and 39 current smokers. The DNA was assessed for EGFR and KRAS mutations. Copy number profiles were generated for each tumor using matched non-malignant lung tissue as a baseline for the identification of somatic copy number alterations. Two datasets composed of lung adenocarcinomas from never-smokers and smokers were used for validation.
On average, people who never smoked had lung tumors that contained a higher frequency of copy number alterations and more altered genomes compared with those of smokers.
This difference became even more pronounced when former smokers were eliminated from the comparison and never-smokers were compared with current smokers only.
This research was presented at the 14th World Conference on Lung Cancer in Amsterdam, hosted by the International Association for the Study of Lung Cancer (IASLC). Until research is published in a peer-reviewed journal, findings are considered preliminary.