London: Scientists have discovered what they claim is a common gene that raises the risk of developing lung cancer in non-smokers, a breakthrough which may pave the way for new targeted therapies for patients.
Despite several attempts to identify the specific genetic mechanisms responsible, the causes of lung cancer in "never-smokers" remain poorly understood.
Now, an international team, led by Mayo Clinic College of Medicine in New York, has identified the gene known as GPC5 which predisposes non-smokers to lung cancer, leading British newspaper `The Times` reported.
In their research, the scientists, led by Ping Yang, examined DNA samples from 754 "never-smokers", and analysed more than 300,000 DNA variants known as single nucleotide polymorphisms (SNP).
These were compared with samples from members of the public matched to patients by age, sex and ethnicity to show the genetic variations most likely to alter the risk of lung
cancer in never-smokers.
The research also analysed possible links to lung cancer while controlling for history of chronic obstructive pulmonary disease, exposure to second-hand smoke, and family
history of lung cancer.
Two specific genetic markers or SNPs emerged as significant. To validate their findings, the scientists took the 44 most frequently occurring genetic alterations from the research and assessed them in two additional independent groups of never smokers.
The two SNPs remained significant in both these replication sets, and further research backed the conclusion that they were associated with lung cancer in non-smokers through how they regulate the expression of the GPC5 gene.
Additional tests showed that GPC5 expression levels were 50 per cent lower in adenocarcinoma (the most common form of lung cancer) than in matched normal lung tissue, indicating that reduced GPC5 activity can be specific for adenocarcinoma in never smokers.
The findings have been published in the latest edition of `The Lancet Oncology`.