Genetic Region Linked to a Five Times Higher Lung Cancer Risk

A narrow region on chromosome 15 contains genetic variations strongly associated with familial lung cancer, says a study conducted by scientists at Washington University School of Medicine in St. Louis and other institutions in the United States and the United Kingdom.

The researchers found a more than five times higher risk of lung cancer for people who have both a family history of the disease and these genetic variations. The risk was not affected by whether the study participants smoked or didn't smoke.

Published in the Sept. 13 issue of the Journal of the National Cancer Institute, this study is the fourth since April 2008 to implicate this genetic region in the development of lung cancer, and it strengthens the possibility that testing for variations in this region could become a valuable way to warn individuals of their higher risk.

"Many smokers don't get lung cancer, which suggests there is a genetic difference in smokers who do get the disease," says senior author Ming You, M.D., Ph.D., a researcher in cancer chemoprevention at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

"We also know that some families have a high incidence of lung cancer. If we can identify the genetic factors linked to lung cancer in such people before they get the disease, we can take steps to help prevent it. This genetic region might be part of the answer."

Lung cancer, the leading cancer killer in the United States, will likely cause 162,000 deaths in 2008 in men and women combined, according to projections. The National Cancer Institute indicates that cigarette smoking is linked to 87 percent of these deaths.

Among research groups studying lung cancer susceptibility, many other genetic markers of increased risk have been identified, but the area identified in this study on chromosome 15 is the only genetic region that is consistent across many studies, You says.

The three other recent studies that identified these specific genetic variations focused on sporadic lung cancer, but the current study established a strong risk factor in this chromosomal region for the kind of lung cancer that is inherited.

Sporadic lung cancer occurs in individuals without a family history of lung cancer, while familial lung cancer, as defined for this study, is lung cancer that occurs in three or more direct blood relatives.

The three recent studies on sporadic lung cancer cited an approximately 30 percent greater risk for individuals with specific genetic variations in this region of chromosome 15, a much lower risk than found in the current study, You notes.
One of these studies indicated that smoking increases the risk when people have the genetic variations on chromosome 15, but two of the studies indicated that smoking adds no increased risk in such people. The increase in risk identified in the current study also was not dependent on whether a person smoked.