Lung cancer tumors in never-smokers differs from those of smokers, study finds

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A genomic analysis of lung cancer in people with no history of smoking found a majority of tumors arising from the accumulation of mutations caused by natural body processes, according to findings published Sept. 6 in Nature Genetics.

About 10 percent to 20 percent of people who develop lung cancer have never smoked. Though environmental risk factors may play a role in some cases, it's still unknown what causes the majority of these cancers.

The large epidemiologic study was led by researchers at the National Cancer Institute, part of the National Institutes of Health. Researchers used whole-genome sequencing to characterize genomic changes in tumor tissue and matched normal tissue from 232 never-smokers who had been diagnosed with non-small cell lung cancer. The tumors included 189 adenocarcinomas, 36 carcinoids and seven other tumors of various types. The patients had not yet been treated for the cancer. 

Researchers found that most of the tumor genomes of never-smokers had mutational signatures linked to damage from natural processes that happen inside the body. They did not find any mutational signatures previously associated with direct exposure to tobacco smoking, nor did they find those signatures among the 62 patients who had been exposed to secondhand smoke.  

The analyses also identified three novel subtypes of lung cancer in never-smokers. 

"What we're seeing is that there are different subtypes of lung cancer in never smokers that have distinct molecular characteristics and evolutionary processes," Maria Teresa Landi, MD, PhD, study lead and epidemiologist with the Integrative Tumor Epidemiology Branch in NCI's Division of Cancer Epidemiology and Genetics, said in a Sept. 6 news release. "In the future we may be able to have different treatments based on these subtypes."

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