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Three-team study finds genetic links to smoking

Smoking causes lung cancer, that much is known. But a trio of new studies published today suggests genes may play a role in why some longtime smokers get the deadly disease and others do not.

At the same time, the scientists say these common genetic variations may also make smokers more likely to become addicted to tobacco and to smoke more cigarettes. These findings, which several experts said represent the first time a genetic variation has been linked to lung cancer, could lead to a greater understanding of how smoking and genes interact to cause the disease.

"I've been calling it the double whammy gene," said Dr. Chris Amos, a genetic epidemiologist at the M.D. Anderson Cancer Center in Houston and lead author of one of the studies. "It increases your lung cancer risk and it also makes it hard for you to quit smoking, makes you more dependent."

Researchers also said the discovery could lead to the development of customized smoking cessation programs for those whose genes may make it more difficult to stop on their own.

The smoking rate among U.S. adults has dropped from 42 percent in 1965 to less than 21 percent now.

All smokers and former smokers have a 15 percent greater risk of developing lung cancer — the deadliest of all cancers — than nonsmokers, researchers said. But smokers who got the genetic variations from both parents have an 80 percent greater risk of developing lung cancer than a smoker without them, the studies show.

People who never smoked but had the genetic quirk were not more susceptible to lung cancer.

"Smoking — it's the overwhelming risk factor whether you have one or two or no variants," said Dr. Kari Stefansson, chief executive of deCODE Genetics in Iceland and author of the largest of the three studies.

Scientists cautioned Wednesday that even if widespread testing could be done for these genetic variations, the public health advice would not change: People who don't smoke shouldn't start, and people who smoke should quit.

The studies — led by researchers in France, Iceland and the United States — are being published in the journals Nature and Nature Genetics.

The research involved only white people of European descent. Blacks and Asians will be studied soon and may yield quite different results, scientists said.

The three groups looked at 35,000 people and came up with similar conclusions about the same region on chromosome 15, a spot known to house nicotine receptors. Two of the research groups said the link is directly between lung cancer and the genes; the other found an indirect route.

According to the researchers from Iceland, there is a correlation between the genetic variation and nicotine dependence and smoking quantity. Being a carrier doesn't make people start smoking, but it makes them smoke more and makes it tougher for them to quit. Those researchers concluded that it is likely that those factors lead to the increase in risk of lung cancer.

But Paul Brennan of the International Agency for Research on Cancer in France, author of another study, said he at first thought that, but was convinced later that "the genes primarily increase the risk of lung cancer by driving forward the process at the cellular level," he said. Nicotine could be the environmental trigger that stimulates actual tumor growth in those with the variation, he said.

Dr. Stephen J. Chanock, chief of the laboratory of translational genomics for the National Cancer Institute, said the studies — even in their somewhat differing conclusions — bring a better understanding of the biology of lung cancer.

"These studies are all pointing in the same place," he said. "They point to places in the genome we didn't know about."

Information from the Associated Press was used in this report.

. Fast facts

Findings

Scientists who discovered a genetic link to smoking addiction and lung cancer have calculated smokers' cancer risk based on whether they have certain genetic variations. The research covered only white people of European descent. It found:

• 23 percent chance of getting lung cancer if the smoker inherited these genetic differences from both parents.

• 18 percent chance of lung cancer if the smoker inherited the genetic differences from one parent.

• 14 percent chance of lung cancer without the genetic variations.

• Less than 1 percent chance of lung cancer for people who have never smoked.

Three-team study finds genetic links to smoking 04/02/08 [Last modified: Thursday, April 3, 2008 6:53am]

    

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