Studies find genes that increase risk of lung cancer
Body's response to nicotine is key element
LOS ANGELES - Three research groups announced yesterday that they have identified a widely distributed genetic variation that appears to increase the odds of developing lung cancer.
Although 80 percent of lung cancer cases are attributable to smoking, scientists have long known that genetics play a role. Family studies have shown that having a parent or sibling with lung cancer doubles or triples the odds of developing the disease.
Yet finding the genes that predispose people to lung cancer has been difficult.
The studies - two in the journal Nature and one in Nature Genetics - implicated a genetic variation located near a cluster of genes on chromosome 15 that are involved in the body's response to nicotine.
The papers said that people who inherit the variation from one parent have a 30 percent greater chance of getting lung cancer. Those who inherit the variation from both parents face an increased risk of 70 percent to 80 percent.
The discovery might help explain why some smokers don't get lung cancer and why some occasional smokers don't become addicted, researchers said.
In general, smokers face a 15 percent chance of developing lung cancer; smokers with one copy of the genetic variation have about the same risk. However, smokers who inherit two copies face about a 1 in 4 chance of getting lung cancer.
The groups detected the variation by analyzing the genomes of more than 35,000 smokers and former smokers, and a smaller number of nonsmokers, almost all of whom were from Europe, Canada, and the United States.
Researchers said about half of the people of European descent have one copy of the variation, which is believed to be much less common in people of Asian or African descent.
The studies were divided on whether the genetic variant directly increased the risk of lung cancer or did so indirectly by predisposing people to smoking.
One of the teams linked the variation to smoking addiction. Study author Kari Stefansson, chief executive of deCode Genetics, a company based in Iceland, said smokers who inherited one variant smoked an average of one more cigarette a day than other smokers. Smokers who inherit two copies smoked an average of two extra cigarettes a day, he said.
Stefansson said it was the extra cigarettes, and not the gene itself, that led to lung cancer. His group estimated that the variation was indirectly responsible for 18 percent of lung cancers and 10 percent of cases of peripheral artery disease, which is also linked to smoking.
"Lung cancer is almost certainly environmentally induced, and we have found the variant that pulls us toward that environment," Stefansson said.
Two teams linked the variation directly to the disease. Paul Brennan of the International Agency for Research on Cancer in Lyon, France, an author of the second study, said there was no link between the variant and smoking addiction. What's more, he said, nonsmokers with a variant had a higher risk of lung cancer compared with nonsmokers without one, Brennan said.
Christopher Amos of M.D. Cancer Center in Houston, lead author of the third study, looked at a larger group of nonsmokers and found no increased risk of lung cancer in those with a variant.
Amos and Brennan said it was possible that the gene variant was triggered by substances in tobacco smoke.
People who have never smoked have a less than 1 percent chance of getting the disease.
Stefansson said his firm, which sells genetic tests, plans to begin marketing a lung cancer screening tool based on the study results.
Stephen J. Chanock of the National Cancer Institute and David J. Hunter of Harvard University, authors of a commentary also published in Nature, said such a test could be used to assess the success of smoking-cessation programs in people predisposed to smoking.
But they warned a test could delude people without the variant into thinking that they were immune to the health risks of smoking, which besides lung cancer include heart disease and pulmonary disease.
