WASHINGTON – Scientists have pinpointed genetic variations that make people more likely to get hooked on cigarettes and more prone to develop lung cancer – a finding that could someday lead to screening tests and customized treatments for smokers trying to kick the habit.
The discovery by three separate teams of scientists makes the strongest case so far for the biological underpinnings of nicotine addiction and sheds more light on how genetics and lifestyle habits join forces to cause cancer.
“This is kind of a double whammy gene,” said Christopher Amos, a professor of epidemiology at the M.D. Anderson Cancer Center in Houston and author of one of the studies. “It also makes you more likely to be dependent on smoking and less likely to quit smoking.”
A smoker who inherits these genetic variations from both parents has an 80 percent greater chance of lung cancer than a smoker without the variants, the researchers reported. And that same smoker on average lights up two extra cigarettes a day and has a much harder time quitting than smokers who don’t have these genetic differences.
The researchers disagreed on whether the variants directly increased the risk of lung cancer or did so indirectly, by causing more smoking.
The three studies, funded by governments in the U.S. and Europe, are being published today in the journals Nature and Nature Genetics.
The scientists studied the genes of more than 35,000 white people of European descent in Europe, Canada and the United States. Blacks and Asians will be studied soon and may yield different results, scientists said.
They aren’t quite sure if what they found is a set of variations in one gene or in three closely connected genes.
The gene variations, which govern nicotine receptors on cells, could eventually help explain some of the mysteries of chain smoking, nicotine addiction and lung cancer. These oddities include why there are 90-year-old smokers who don’t get cancer and people who light up an occasional cigarette and don’t get hooked.
“This is really telling us that the vulnerability to smoking and how much you smoke is clearly biologically based,” said psychiatry professor Dr. Laura Bierut of Washington University in St. Louis, a genetics and smoking expert who did not take part in the studies. She praised the research as “very intriguing.”
The smoking rate among U.S. adults has dropped from 42 percent in 1965 to less than 21 percent now.
The new studies are surprising in that they point to areas of the genetic code that are not associated with pleasure and the rewards of addiction.
That may help explain why some people can quit and others fail, said Dr. Nora Volkow, director of the National Institute of Drug Abuse in Bethesda, Md., which funded one of the studies.
“It opens our eyes,” Volkow said Wednesday. “Not everyone takes drugs for the same reason. Not everyone smokes cigarettes for the same reasons.”
One clue is in the location of the just-discovered variants, on the long arm of chromosome 15, Volkow said. It is in an area that, when damaged during tests on animals, makes them depressed and anxious. While some people smoke because it helps them focus or gives them a physiological reward, others do it to stave off depression.
That suggests that adding antidepressants to some smokers’ treatment could help them kick the habit.
Bierut said a simple, inexpensive test could be developed to screen people for the variants. Kari Stefansson, lead author of the largest of the three studies, agreed. He is chief executive of deCode Genetics of Iceland, which already does prostate cancer genetic tests.