News from the 14th World Conference on Lung Cancer
The 14th World Conference on Lung Cancer (WCLC 2011) hosted by the International Association for the Study of Lung Cancer (IASLC) took place in Amsterdam began July 3 and continues through July 7. The IASLC issued a statement on the use of spiral CT screening for lung cancer, acknowledging the recently published article in the New England Journal of Medicine which highlighted the results from the National Lung Screening Trial (NLST) which showed that lung cancer deaths fell by 20% and all-‐cause mortality fell by 7% when smokers were screened regularly using low-dose spiral CT scans compared to standard x-ray.
The IASLC states it is appropriate for heavy smokers (current or former smokers with 30 or more pack years of smoking) ages 55 to 74 to discuss relevant lung cancer screening with their physicians to assist them in deciding whether to undergo a spiral CT screening.
At a session on Monday at the WCLC 2011, researchers discussed the shift seen with mapping the lung cancer epidemic, both statistically and genetically, from squamous cell carcinoma (SCC) to adenocarcinoma (ADC) as the leading type of lung cancer.
Douglas Flieder, Fox Chase Cancer Center, USA, addressed cigarette evolution as the main reason for the displacement of SCC
by ADC as the leading lung cancer subtype. The development of filters makes smokers inhale more deeply, bringing smoke to the sites of adenocarcinogenesis. And low tar/low nicotine cigarettes cause smokers to puff more often, inhaling a greater volume per
puff. The rise in ADC incidence has also been linked to the availability of blended reconstituted tobacco.
Richard Peto, Clinical Trial Service Unit & Epidemiological Studies Unit, UK, emphasized the importance of stopping on lifetime lung cancer risk: "A recent study showed women who smoke 20 cigarettes per day have a risk of developing lung cancer 30 times higher than non-smokers."
Quitting before age 50 reduces the risk to six times higher, and quitting before 40 reduces it to 1.2 times higher, almost eliminating the effect of smoking altogether.
Research presented by Kelsie Thu, BC Cancer Agency Research Centre in Vancouver, Canada, and colleagues shows lung adenocarcinomas in people who have never smoked show greater genome instability than those in smokers, supporting the theory that lung cancer in never smokers arises through different pathways.
Thu states, "We identified several genomic regions that were differentially altered in the lung tumor genomes of smokers and never smokers. We also found that a greater fraction of lung tumor DNA harbored genetic alterations in never smokers compared to smokers. The discovery that there are different patterns of genetic alterations in smokers and never smokers suggests that lung cancers in these cohorts are likely distinct diseases driven by different molecular mechanisms, and thus, may require different treatments."
Up to 25% of lung cancer cases worldwide occur in people who have never smoked, and never smokers with lung cancer typically exhibit traits different from those of smokers. They are more often women, Asian, have a higher incidence of epidermal growth factor receptor (EGFR) mutations, better responses to EGFR-targeting drugs and are more commonly diagnosed with adenocarcinoma.
In the study, Thu and colleagues extracted 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 independent, publicly available datasets composed of lung adenocarcinomas from never smokers and smokers were used as validation datasets.
On average, never smokers' lung tumors showed higher frequencies of copy number alterations and greater proportions of altered genomes compared with those of smokers. This difference was more pronounced when former smokers were excluded and never smokers were compared with current smokers only.