Comparing lung cancer in never smokers and smokers

Nov. 17, 2021

For the first time, researchers at Moffitt Cancer Center have identified unique genetic signatures of lung cancer in people who have never smoked cigarettes. The new study, published in Nature Genetics, more than doubles the number of sequenced lung tumors from never smokers, resulting in new opportunities for early detection and treatment, according to a news release from Moffitt.

The study, dubbed the Sherlock-Lung study, conducted an in-depth genomic analysis of the tumors from 232 never smokers with lung cancer.

The study identified three genetic subtypes unique to never smokers, which were named piano, mezzo-forte and forte, after the musical terms assigned to loudness. The “piano” tumors are the quietest and have the least number of mutations, growing extremely slowly over a number of years. “Mezzo-forte” tumors demonstrate mutations in the growth factor receptor gene EGF, which is commonly found in lung cancers, and exhibit faster tumor growth. The “forte” subtype is the loudest, grows the quickest and is most similar to lung cancers among smokers.

Many of the exposures associated with lung cancer risk are risk factors for both smokers and never smokers, such as advanced age, second-hand smoke, cooking fumes, ionizing radiation, radon gas, inherited genetics, occupational exposures and preexisting lung diseases like COPD. While lung cancer screening is not approved for never smokers, research is underway at Moffitt to develop artificial intelligence methods to help reveal which never smokers are at the greatest risk of lung cancer and may benefit from lung cancer screening.

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