Lung Cancer: Researchers Find Three Subtypes of Tumors in People That Never Smoked

Doctors at the National Cancer Institute in Bethesda Maryland have discovered more facts about the development of lung cancer in people who have never smoked.

Lung Cancer

Lung cancer is one of the most common cancers in the US. Smoking increases the risk of developing lung cancer on average tenfold by the age of 66. Even non-smokers can get it. Exposure to asbestos, air pollution, or radon can also cause lung cancer. The link between exposure to environmental factors and the development of lung cancer in non-smokers is not always proven. It can occur for no apparent reason.

A team of Americans and Canadians carried out a genomic analysis of cancerous lung tissue taken from people who had never smoked. The doctors were able to identify three subtypes of lung cancer common in non-smokers and their origins. The results were published in Nature Genetics.

A total of 232 tumor tissue samples were analyzed. Doctors sequenced the genome of all tumor cells and compared mutation patterns in diseased and healthy tissue. Three subtypes of lung cancer were identified and classified according to the number of changes in the genome.

Firstly, the mutations detected do not correspond to those caused by smoking or passive smoking. They are endogenous, occurring either through natural mutation or through oxidative stress experienced by all cells. To use a musical metaphor, the three subtypes are named ‘piano’, ‘mezzo forte’, and ‘forte’. “The ‘piano’ subtype, which constituted the majority of the samples analyzed, is characterized by slow growth and the presence of several mutated genes, such as UAB1 or KRAS.

The second subtype, ‘mezzo forte’, is characterized by the amplification of some genes, i.e. the presence of additional copies of the gene, and mutations in the EGFR gene, which encodes the EGF (epidermal growth factor) receptor. Mutations in this receptor are associated with several cancers, including lung and breast cancer. When deregulated, it promotes uncontrolled cell proliferation. Mesoforte lung cancer grows rapidly.

Finally, the ‘forte’ subtype is characterized by polyploidy. In these cancers, the entire genome is duplicated (whole genome duplication). They are no longer diploid (two copies of each gene) but polyploid with at least three copies of the genome.

“We are only beginning to understand how these tumors develop. This analysis shows that lung tumors in people who have never smoked are heterogeneous or diverse,” explains Dr. Maria Teresa Landi from the National Cancer Institute in Bethesda and principal investigator of this study. This research could improve cancer treatment for non-smokers.