About 30 percent of lung cancer patients who never smoked had the same uncommon variant, or allele, residing in a gene known as GPC5.

A five-center collaborative study that scanned the genomes of thousands of "never smokers" diagnosed with lung cancer, as well as healthy never smokers, has found a gene they say could be responsible for a significant number of those cancers.

"This is the first gene that has been found that is specifically associated with lung cancer in people who have never smoked," study lead investigator, Ping Yang, M.D., Ph.D., Mayo Clinic genetic epidemiologist, was quoted as saying.

The research was co-led by scientists at the Mayo Clinic in Minnesota, Harvard University, University of California at Los Angeles (UCLA) and MD Anderson Cancer Center. Researchers found that this allele leads to greatly reduced GPC5 expression, compared to normal lung tissue. The finding suggests that the GPC5 gene has an important tumor suppressor-like function and that insufficient function can promote lung cancer development.

"It has been very hard to do this research because never smokers have been mingled with smokers in past studies, and what usually pops up are genes related to nicotine dependence," said Dr. Yang. "Findings from this study concern pure lung cancer that is not caused by smoking, and it gives us some wonderful new avenues to explore."

A never smoker is defined as a person who has smoked fewer than 100 cigarettes in his or her lifetime, and that describes 15 percent of men and 53 percent of women who develop lung cancer -- accounting for 25 percent of all lung cancers worldwide, according to Dr. Yang. In the Western countries, between 10 and 15 percent of lung cancers occur among never smokers, but in Asian countries, 30 to 40 percent of lung cancers are never smokers, she says. "Our suspicion all along is that this is a distinct disease, and that is why we undertook this study," said Dr. Yang.

"If reduction of expression of this gene leads to development of lung cancer, it suggests that this gene is normally a tumor suppressor," said Dr. Yang. "We believe it helps control the cell proliferation and division, but we need to prove its function in animal models."

The researchers calculated that about one-third of never smoker lung cancer patients in this study had the same variation of the underperforming GPC5 gene. "We hypothesize that this is an important cancer trigger in these patients," she said, "and that something else is going on in the remaining two-thirds of never smokers. We don't know what that is, but we now have 42 other hits to explore."

Source: Lancet Oncology, published online March 22, 2010