Project TEAM

Special Populations: Genes and Tobacco Use

Almost fifty years ago, a researcher suggested that there might be a genetic predisposition to smoking and lung cancer that explained why teens began smoking and why their lungs later, when they were adults, were found to have tumors. Today we know that genetic factors do affect vulnerability to tobacco use and dependence, but we also know that the genes that predispose to dependence are not the same ones that cause lung cancer.

To learn more about genetic predisposition to smoking and to separate genetic factors from environmental influences, researchers have relied on studies of twins reared apart, adopted children, and genome mapping; compared adopted sibling pairs to biological sibling pairs; and investigated genes thought to be candidates for explaining susceptibility to smoking dependence. What they have found is that genes appear to explain tobacco dependence in part, but that more research is needed to understand the mechanisms at work.

Researchers have found, for example, that there are stronger associations between family members and the number of cigarettes consumed than there are between individuals who are not biologically related and the average number of cigarettes consumed. Correlation coefficients ranged from 0.52 for identical twins and 0.30 for fraternal twins to 0.05 for adoptive siblings and -0.02 for adoptive parents and adoptive offspring. In addition, research in families has consistently shown that family members of smokers are more likely to be smokers than are family members of nonsmokers. Though it must be understood that environmental effects were not accounted for in the research design, one study showed that people with a nicotine-dependent sibling were 2.1 to 3.5 times more likely to also be nicotine dependent than were those who did not have a nicotine-dependent sibling.

In twin studies, researchers reasoned that identical twins, because they have greater genetic concordance, are likely to have greater concordance in their tobacco habits than are fraternal twins. Results supported researchers' hypotheses: identical twins did demonstrate greater concordance in their tobacco use behavior than did fraternal twins. Tobacco use included being a nonsmoker, smoking, quitting smoking, and the amount smoked. Furthermore, they estimated average heritability of smoking to be 0.53 (range, 0.28–0.84); therefore, the researchers concluded that about half of the variance in smoking is owed to genetic factors. Kendler, Thornton, and Pederson (2000) reported similar findings in a study of twins reared apart. Studying these highly genetically concordant twins reared in different environments allowed researchers to more reliably differentiate between environmental and genetic influences. They attributed to genetic factors 60% of the variance in regular smoking in men and women born after 1940.

Research here at M. D. Anderson Cancer Center in genetic factors affecting tobacco use includes work by Drs. Cinciripini, Spitz, and Wu who with colleagues examined the prevalence and functional significance of polymorphisms in the DRD2 gene as part of ongoing work. They found that the B1 allele was more prevalent in current and foreign smokers than in nonsmokers. Later work is thought to be the first study to show a link between participants' genetic background and response to an antidepressant drug.

These are just a few of the studies under way to define better the link between genetics and tobacco use. This other initial work is beginning to reveal findings with implications for cessation interventions:

• Smokers with the DRD2 A1 allele are less likely to quit than are smokers with the DRD2 A2 allele.
• Dopamine receptor genes and the dopamine transporter gene appear to have an effect on nicotine dependence.
• While taking the antidepressant venlafaxine, smokers with the DRD2 A2 allele experienced less reduction in negative mood than did smokers with the A2 allele.

<< back Page 6 of 9 next >>