Montreal - A faulty gene may lead some young teenage smokers to be even more susceptible to years of nicotine addiction, a new study suggests.

A variation in a single gene -- called CYP2A6 -- slows nicotine metabolism in the liver, resulting in prolonged brain exposure to the drug. Researchers found that teens with the genetic variation were more likely to become nicotine dependent, even though they smoked fewer cigarettes per week than those with the normal gene. These findings complement the results of a previous study on nicotine dependency among teens, said lead author Jennifer O'Loughlin, a McGill University epidemiologist who studies tobacco use among children and teenagers. The result raises "huge alarm bells" about what prompts people to take up smoking, Dr. O'Loughlin said yesterday. "There's no equivocal message here. There's no safe level of smoking for teenagers," she said in an interview. "The first puff is dangerous." The $800,000 study, which she described as the first of its kind among adolescents, is to be published on-line in today's issue of Tobacco Control. The research was funded by the National Cancer Institute of Canada, the research arm of the Canadian Cancer Society. Previous research has shown that those who become chemically dependent on nicotine have a harder time quitting smoking. The new findings add to the complicated puzzle about teen smoking, said Cheryl Moyer, director of cancer-control programs for the cancer society. "The more we understand about the process and how different people move through the process of smoking, the more we can start trying to think about target messages instead of this one broad approach for everybody," she said. Dr. O'Loughlin has followed nearly 1,300 Montreal teens since 1999 as part of a study on genetic and environmental risk factors for nicotine dependence in youth. For this part of the study, DNA from blood samples from 281 of students who smoked were analyzed for CYP2A6. The students, who were about 12 when the study started, also completed quarterly questionnaires that measured their smoking patterns and nicotine dependence, including withdrawal symptoms and cravings. Researchers said they don't feel it's ethical to notify students who have the defective gene. Nineteen per cent of the students tested had an altered version of the gene. Among the students with the slowest nicotine metabolism, the risk of becoming tobacco dependent was three times higher than among normal metabolizers. Students with the normal gene smoked an average of 29 cigarettes per week. Those whose genes made them most susceptible to addiction smoked just 12 cigarettes a week. Last year, Dr. O'Loughlin published findings from the same sample of students showing that teens who smoked only once or twice reported common symptoms of nicotine addiction. She said other researchers are now attempting to determine if drugs can be used to mitigate the slower metabolism among those with the defected gene.

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