The genetics of nicotine dependence: relationship to pancreatic cancer.
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.
MacLeod
Stewart L
SL
Department of Pediatrics, University of Arkansas for Medical Sciences, 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
Chowdhury
Parimal
P
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011954:Receptors, Dopamine / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012907:Smoking / Q000009:adverse effects; D014029:Tobacco Use Disorder / Q000150:complications* / Q000235:genetics*
D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D050486:Serotonin Plasma Membrane Transport Proteins; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D019389:Cytochrome P-450 CYP2D6; D004298:Dopamine