Skip to nav Skip to content

Historically, lung cancer has largely been considered a smoking-related disease. However, as the smoking population decreases, there has been an increase in lung cancer detected in those who have never smoked. In the U.S. about 10%-20% of all lung cancer diagnoses occur in never smokers.

“If considered as a separate reportable category, lung cancer in never smokers would be the 11th most common cancer and the seventh leading cause of cancer-related deaths,”  said Dr. Matthew Schabath, a lung cancer epidemiologist at Moffitt Cancer Center.

So, what makes disease among never smokers different?

For the first time, researchers 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.

Dr. Matthew Schabath, cancer epidemiologist

Dr. Matthew Schabath, cancer epidemiologist

The study, dubbed the Sherlock-Lung study, conducted an in-depth genomic analysis of the tumors from 232 never smokers with lung cancer. “We searched the tumor genomes for known mutational signatures, which are patterns of mutations that can provide clues into what caused these cancers to develop,” said Schabath, one of study’s authors.  “For example, there are specific mutational signatures associated with direct exposure to tobacco smoking or diesel exhaust.”

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.

“Our hope is this research will guide the development of more precise clinical treatments that will benefit never smoking patients with lung cancer,” said Schabath.

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.