NCI Tobacco Control Monograph Series
September 2009 U.S. National Institutes of Health

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Monograph 20 Communication Toolkit - Drop-in Article

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Phenotypes and Endophenotypes: Foundations for Genetic Studies of Nicotine Use and Dependence

Although tobacco use in the United States has steadily declined since the 1980s, an estimated 45 million people in the United States still smoke. Worldwide millions of people die each year from illnesses caused by tobacco use. Tobacco use behavior is dependent on complex genetic and environmental influences and interactions that are currently not well understood. Identifying phenotypes (observable traits determined by groups of genes) and endophenotypes (measurable components along the pathway between genes and the condition of interest) for smoking behavior may help guide future research, tailor treatments for individual smokers more effectively, and enhance existing public health policy in tobacco prevention and control.

"This monograph addresses the need for improved phenotypes of nicotine dependence, makes important advances in behavioral genetics, and demonstrates the potential contribution of genetics research to tobacco control," said Stephen E. Marcus, Ph.D., Monograph Series Editor, Tobacco Control Research Branch, National Cancer Institute.

National Cancer Institute's Tobacco Control Monograph 20, Phenotypes and Endophenotypes: Foundations for Genetic Studies of Nicotine Use and Dependence reviews the scientific foundation for genetic studies of nicotine use and dependence. The authors and editors—representing a wide range of expertise in the fields of psychology, psychiatry, behavioral pharmacology, neurobiology, epidemiology, statistical genetics, and bioinformatics—reviewed and analyzed the growing body of research findings in the field to develop a scientific plan for incorporating genetic research into crossdisciplinary studies of nicotine dependence.

In developing this NCI monograph, the editors and authors accomplished several major "firsts" in the field of genetic research and nicotine dependence:

  • First comprehensive review of the broadly relevant literature.
  • First demonstration that differences in tobacco-use trajectories-from early adolescence to early mid-life-are related to both family history of smoking and nicotine dependence in adulthood.
  • First demonstration that conjoint trajectories of tobacco and alcohol use in adolescents can be inherited.
  • First identification of biobehavioral phenotypes that can be used in future genomic studies of adolescents and adults pre- and post-nicotine exposure.
  • First demonstration that microcontextual effects on nicotine dependence can be assessed and are informative in genomic studies.
  • First use of Bayesian analysis to determine the relative importance of several genes to variations in nicotine metabolism.

"This monograph is a culmination of several years' worth of thinking by the leading scientists working in this field. Our goal in publishing this monograph is to stimulate the reader to incorporate newer, more specific indicators of nicotine dependence along with measures of environmental risk factors into future studies on the genetics underlying this treatable condition. By doing so, new insights into the genesis and treatment of nicotine dependence will emerge," Gary E. Swan, Ph.D., Senior Scientific Editor and Director, Center for Health Sciences, SRI International.

The latest in the Tobacco Control Monograph series, this NCI monograph provides important, innovative, and new concepts and methodologies for behavioral genetics. Monograph 20 makes a strong case for continued and expanded research of genetic influences on tobacco use. A better understanding of the role of genetic susceptibility may help the public health community enhance already effective public policies for tobacco prevention and control. Placed into the context of what is known to already work, the knowledge gained from genetic studies may play an important role in the future development of environmental and policy interventions.

"This monograph is a culmination of several years' worth of thinking by the leading scientists working in this field. Our goal in publishing this monograph is to stimulate the reader to incorporate newer, more specific indicators of nicotine dependence along with measures of environmental risk factors into future studies on the genetics underlying this treatable condition. By doing so, new insights into the genesis and treatment of nicotine dependence will emerge," Gary E. Swan, Ph.D., Senior Scientific Editor and Director, Center for Health Sciences, SRI International.

The latest in the Tobacco Control Monograph series, this NCI monograph provides important, innovative, and new concepts and methodologies for behavioral genetics. Monograph 20 makes a strong case for continued and expanded research of genetic influences on tobacco use. A better understanding of the role of genetic susceptibility may help the public health community enhance already effective public policies for tobacco prevention and control. Placed into the context of what is known to already work, the knowledge gained from genetic studies may play an important role in the future development of environmental and policy interventions.

View the full text of the monograph online at http://cancercontrol.cancer.gov/brp/tcrb/monographs/20/index.html or order the publication by calling the NCI Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).Ask for NIH Publication No. 09-6366.

The NCI began the Tobacco Control Monograph Series in 1991 to provide ongoing and timely information about emerging issues in tobacco prevention and control. Recent titles include: The Role of the Media in Promoting and Reducing Tobacco Use; Greater Than the Sum: Systems Thinking in Tobacco Control; Evaluating ASSIST - A Blueprint for Understanding State-level Tobacco Control; and ASSIST - Shaping the Future of Tobacco Prevention and Control. To view past monographs, visit http://cancercontrol.cancer.gov/brp/tcrb/monographs/

Tobacco Control Research Branch
Behavioral Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
National Institutes of Health
Bethesda, MD

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