A new study, by researchers from the University of Taxes Southwestern Medical Center, has found that lung cancer patients who have never smoked are more likely than smokers to harbour one of two genetic mutations that are linked to the disease.
This substantiates the suspicion that an individual smoker’s genes can help determine his or her risk of getting lung cancer.
This study, which spanned lung cancer patients from the United States, Australia, Taiwan, and Japan and entailed studies on 600 lung tumours, concluded that mutations in a specific domain of the epidermal growth factor receptor (EGFR) gene had an occurrence rate of 51 per cent in people who didn’t smoke, as compared to 10 per cent in those who did.
During the research, Dr Gazdar and his team analysed tissue samples from primary tumours of 519 patients. In addition, mutations in the DNA of non-malignant lung tissue from many of these patients and from other cancer tissues were examined. The results showed that mutations in the EGFR gene had a higher rate of occurrence in lung cancer patients who never smoked as compared to smokers.
The occurrence in adenocarcinomas was 40 per cent compared to other lung cancers, where it was 3 per cent. Women showed higher cases of mutation as compared to men. Also, patients with Asian ancestry showed 30 per cent mutation in EGFR gene as compared to other ethnicities, where it was hardly 8 per cent.
Dr Adi Gazdar, professor at Nancy B and Jake L Hamon Center for Therapeutic Oncology Research and senior author of the study, said that the new study describes the first known mutation to occur in lung cancer patients who have never smoked. He added that these findings might help explain why certain lung cancer patients respond well to a specific form of targeted therapy, while others have little or no response.
Mutations in the epidermal growth factor receptor (EGFR) gene are present mainly in adenocarcinomas, the most common form of lung cancer. These mutations have shown increased sensitivity to gefitinib (Iressa) and erlotinib (Tarceva), drugs targeting the gene.
Mutations in the KRAS gene, which is essentially a gene in the EGFR signalling pathway, were found in 8 per cent of lung cancers but in none with the EGFR mutation. This mutation was more common in males, Caucasians, and those who were smokers or had been smokers in the past.
According to Dr Gazdar, results indicated that two distinct molecular pathways were involved in the formation of lung cancer. In smokers, the pathway involved KRAS gene mutations, while the pathway in in non-smokers involved EGFR gene mutations.
The next step now is to use these findings to develop better treatments for lung cancer, Dr Gazdar said.
