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World J Gastroenterol. Dec 14, 2006; 12(46): 7433-7439
Published online Dec 14, 2006. doi: 10.3748/wjg.v12.i46.7433
The genetics of nicotine dependence: Relationship to pancreatic cancer
Stewart L MacLeod, Parimal Chowdhury
Stewart L MacLeod, Department of Pediatrics, University of Arkansas for Medical Sciences, and Arkansas Children’s Hospital Research Institute, Arkansas Center for Birth Defects Research and Prevention, Little Rock, AR, United States
Parimal Chowdhury, Department of Physiology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
Author contributions: All authors contributed equally to the work.
Correspondence to: Stewart MacLeod, PhD, Department of Pediatrics, UAMS College of Medicine, Arkansas Center for Birth Defects Research and Prevention, 1120 Marshall St. Mail Slot 512-40, Little Rock, AR 72202, United States. macleodstewartl@uams.edu
Telephone: +1-501-3644586 Fax: +1-501-3645107
Received: July 29, 2006
Revised: September 15, 2006
Accepted: September 29, 2006
Published online: December 14, 2006
Abstract

Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled case-control studies to identify target genes and deduce mechanisms that account for the genetic basis of inter-individual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.

Keywords: Smoking; Pancreatic cancer; Nicotine dep-endence; Genetics; Polymorphism; Nicotine metabolism