Nicotine is an addictive stimulant found in cigarettes and other forms of tobacco. Tobacco smoke increases a user's risk of cancer, emphysema, bronchial disorders, and cardiovascular disease. The mortality rate associated with tobacco addiction is staggering. Tobacco use killed approximately 100 million people during the 20th century and, if current smoking trends continue, the cumulative death toll for this century has been projected to reach 1 billion.
If so many smokers want to quit, why are few able to do so successfully? To address this question, scientists are increasingly focusing on the powerful role of genetics in addiction. Twin studies indicate that approximately 40–70 percent of a person’s risk of becoming addicted to nicotine depends on his or her genes. Although complex diseases like addiction involve large numbers of genes interacting with a wide variety of environmental factors, the contribution of a particular gene can be substantial.
Genetic variants associated with nicotine metabolism, for example, have been shown to influence how people smoke. Slow metabolizers smoke fewer cigarettes per day and have a higher likelihood of quitting, and that there is greater abstinence among individuals receiving nicotine patch therapy. A recent NIDA-funded study identified a variant in the gene for a nicotinic receptor subunit that doubled the risk for nicotine addiction among smokers. A subsequent study found that this gene variant also increased susceptibility to the severe health consequences of smoking, including lung cancer and peripheral arterial disease. NIDA is currently supporting large-scale genome-wide association studies to uncover additional genetic risk factors in order to better understand tobacco addiction and its adverse effects on health.
In addition to predicting an individual’s risk for nicotine addiction, genetic markers can also help predict whether medications (like bupropion) will effectively help a smoker quit. This takes root in the emerging field of pharmacogenomics, which investigates how genes influence a patient’s response to drugs and medications. In the future, genetic screening could help clinicians select treatments, adjust dosages, and avoid or minimize adverse reactions, tailoring smoking cessation therapies to an individual’s unique genetic inheritance.