Genes tied to cigarette addiction

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 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. 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, paid for by governments in the U.S. and Europe, are being published 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.

Unknown factor

The researchers aren't 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 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 professor Dr. Laura Bierut of Washington University in St. Louis, a genetics and smoking expert who did not take part in the studies. The smoking rate among U.S. adults has dropped from 42 percent in 1965 to less than 21 percent.

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.

Testing risks

Such testing could carry risks of its own, bioethicist Arthur Caplan of the University of Pennsylvania warned. People who have been found to have a genetic predisposition to addiction and lung cancer could find it harder to get health or life insurance, he said.

"The good news is that getting these risk estimates will help focus anti-smoking campaigns, and some people will want to voluntarily get into anti-addiction programs early, where they will probably work better," Caplan said.

Smoking-related diseases worldwide kill about one in 10 adults, according to the World Health Organization.

Among other findings:

• Smokers who get the set of variants from only one parent see a risk of lung cancer that is about one-third higher than that of people without the variants. They also smoke about one more cigarette a day on average than other smokers. This group made up about 45 percent of the population studied.

• Smokers who don't have the variants are more than 10 times more likely to get lung cancer than nonsmokers. Smokers without the variant have about a 14 percent risk of getting lung cancer. The risk of lung cancer for people who have never smoked is less than 1 percent, said another study author, Paul Brennan of the International Agency for Research on Cancer in Lyon, France.

Brennan and Amos, working on different teams, linked the genetic variation itself — when triggered by smoking — directly to lung cancer.

Brennan said the nicotine receptors that the variants act on also can stimulate tumor growth. But Stefansson said the increased lung-cancer risk was indirect: The variants led to more smoking, which led to more cancer.