Scientists have identified dozens of mutations that increase the risk of lung cancer, even if their carriers do not smoke. The results of the study were published in the scientific journal Nature Genetics.

“Non-smokers are characterized by several subtypes of lung cancer that are associated with specific sets of mutations and evolutionary processes. In the future, understanding their mechanisms will help us develop different approaches to treat these tumor subtypes,” said NCI lead researcher Maria-Theresa Landi, whose words are cited by the institute’s press service.

In recent years, scientists have discovered dozens of gene variations that affect both a person’s propensity to smoke or his ability to quit cigarettes, as well as the consequences of tobacco abuse. In particular, variations in the CHRNA5 and CYP2A6 genes, which control nicotine elimination from the body, strongly affect the chances of quitting smoking, and mutations in the AhR gene determine how negatively tobacco smoke affects lung tissue.

In the new study, geneticists led by Landi conducted one of the first large-scale studies of genetic risk factors associated with forms of lung cancer whose appearance is not related to smoking or the effects of smoke on respiratory cells. Typically, these tumor variations affect non-smokers and are extremely rare among smokers.

The genetic roots of lung cancer
Lundy and her colleagues studied the genomes of more than 230 samples of such tumors from patients who had never smoked before. The scientists isolated sets of small mutations in the DNA of these tumors, compared them to each other and compared them to the distinctive features of these neoplasms.

Scientists found that there are several dozen mutations that are characteristic of such forms of tumors and are extremely rare in lung tumors in smokers. In particular, carriers of the so-called “piano” forms of lung cancer often had small changes in the structure of the UBA1 gene, which plays an important role in the folding process of various protein molecules.

They also often had mutations in the KRAS gene and associated DNA regions. But there were relatively few changes in other regions of the genome. The other two lung cancer subtypes, called “forte” and “mezzo forte,” were characterized by mutations in the EGFR gene, as well as complete genome doublings and other major shifts in DNA structure.

By further studying these sets of mutations, Lundy and her colleagues hope, it will be possible to elucidate the mechanism behind these lung cancer subtypes. This, in turn, will allow scientists to create new, more effective methods of suppressing the growth of these tumors that are best adapted to combat these cancers.