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Cigarette smoking remains the leading preventable cause of premature death, accounting for one in every five deaths in the United States, many of these due to cancer. NCI supports research to identify factors that contribute to smoking initiation, cancer development, and successful quitting, as well as tools to help people quit, including those available at http://www.smokefree.gov and through NCI's smoking quitline at 1-877-44U-QUIT.
Efforts to stop people before they start smoking have identified peer smoking, family members who smoke, and tobacco industry marketing and advertising as important influences, and there has been some progress in targeting these factors.
However, 22 percent of high school students and 21 percent of adults continue to smoke, and as researchers are beginning to realize, this may have something to do with their genes.
"Genetic factors associated with nicotine dependence and addiction might have an influence on who maintains tobacco use," said Dr. Gary Swan, director of the Center for Health Sciences at SRI International in Menlo Park, CA, and an NCI-funded expert whose research focuses on nicotine dependence, genetic and environmental determinants of addiction, and pharmacogenetics.
Genetic research, for example, has identified variants in the CYP2A6 gene associated with nicotine metabolism. Some people with these variants are able to metabolize nicotine faster with fewer unpleasant side effects, such as nausea and headache, and thus are more likely to become a regular smoker. Conversely, individuals who metabolize nicotine slower are less likely to become regular smokers because the adverse side effects they experience help them resist further use.
Other research is showing that nicotine dependence might be associated with a genetic variant in the dopamine pathway, which regulates feelings of pleasure and reward. People with fewer dopamine receptors are more likely to become regular smokers, presumably because the rewarding effect of nicotine compensates for the lack of dopamine receptors.
Knowledge of genetic variants such as these may eventually help researchers tailor cessation drug treatments according to an individual's genetic makeup, as well as identify new targets for these drugs.
"These fields are still pretty young," said Dr. Swan. "They've only been in operation for about 8 years, with most of the activity in the last 4 years. Compared to cancer genetics, which began in the 1970s with the declaration of the 'war on cancer,' we have a long way to go."
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