Longterm smoking linked to gene

For most people, the first experimental drags on a cigarette bring on nausea, coughing and other signals from the brain that say, "Turn back. This is a bad idea." But for some, they bring a wave of pleasure.

Those in the second group likely bear a gene type that not only increases their addiction risk, but has been implicated in the development of lung cancer, researchers said on Friday.

"If you have this variant, you are going to like your earliest experiences with smoking," said Ovide Pomerleau of the University of Michigan Medical School, whose research appears in the journal Addiction.

Pomerleau said the finding suggests that for some, smoking even one cigarette is a bad idea. "It's a trap," he said in a telephone interview.

"What they don't realize is if they have this kind of genetic make-up, they are on their way to dependency," he said, and that raises their risk for lung cancer.

The research is part of a growing understanding of genetic factors involved in nicotine addiction and lung cancer.

Teams of scientists reported earlier this year that smokers who had certain changes in three nicotine receptor genes -- which control entry of nicotine into brain cells -- were more likely to develop lung cancer than other smokers.

This week, Canadian researchers said that, by manipulating receptors for the chemical dopamine, they were able to control which rats in a study enjoyed their first exposure to nicotine and which were repelled by it.

Pomerleau said the field may soon lead to new treatments for nicotine addiction and tests to assess addiction risks.

Smoking causes nine out of 10 cases of lung cancer, the leading cause of cancer death in men worldwide and the second-leading cause of cancer death among women.

Pomerleau and colleagues studied data from 435 people. Some had tried a cigarette but never developed a habit; others smoked at least five cigarettes a day for the past five years.

Regular smokers in the study were far more likely than those who had never smoked to have a change in the CHRNA5 nicotine receptor gene. Smokers were eight times more likely to report liking cigarettes from the start.

Pomerleau said work has begun to develop a genetic screen for the CHRNA5 variant. Two other researchers on the team, Laura Bierut and John Rice at Washington University, hold a patent on the gene variant, which has been licensed by privately held Perlegen Sciences Inc.

Pfizer Inc, maker of the smoking cessation drug Chantix owns a $50 million stake in Perlegen.

Pomerleau, who has served on Pfizer's scientific advisory board, said he favors development of diagnostic tests, as long as people understand it is not the only risk factor for nicotine addiction.

"What we don't know is far greater than what we do know," he said.

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