The genetics of smoking and smoking cessation

Author and presenter:
Marcus Munafò
Reader in Biological Psychology, Department of Experimental Psychology, University of Bristol, UK

Abstract
As the neurobiology of smoking behaviour is becoming increasingly well-understood, putative candidate genes related to key neurotransmitter and metabolic pathways have begun to be investigated in relation to various aspects of smoking behaviour. One possible clinical implication of research of this kind is that smoking cessation treatment, in particular pharmacotherapy, may in future be ‘tailored’ to individuals on the basis of their specific genotype in order to maximise their likelihood of success in quitting. Treatment parameters such as specific pharmacotherapy, dosage, etc. may then be specified in relation to the genotype of the individual patient.

The current state of evidence for the role of specific candidate genes in smoking behaviour and nicotine addiction will be assessed, with reference to the findings of a recent meta-analysis which concluded that the evidence for a contribution of specific genes ‘remains modest’. Recent findings which have investigated the association of genotype with smoking cessation treatment response will also be reviewed.

Although evidence for a role of specific genes in relation to smoking cessation remains limited at present, there exist several strong candidate genes with known functional effects on relevant neurotransmitter pathways. These candidate genes, and evidence from recent genomewide association studies, will be reviewed with specific reference to the prediction of treatment response. Finally, the potential clinical utility of a pharmacogenetic approach to ‘tailored’ treatment for smoking cessation will be reviewed, including the social and ethical implications of this approach, and whether this is likely to be more cost-effective than current approaches.

Source of funding: Cancer Research UK, Medical Research Council, Wellcome Trust.

Declaration of interest: none

About the presenter
Marcus Munafò was an undergraduate at the University of Oxford, before moving to the University of Southampton to complete a MSc in Health Psychology and a PhD. Following this, he returned to the University of Oxford, as a postdoctoral fellow in the Department of Public Health and Primary Care and later the Department of Clinical Pharmacology. In 2004 – 2005 he was Visiting Professor at the University of Pennsylvania, and in March 2005 took up a tenured position in the Department of Experimental Psychology at the University of Bristol, where he is currently Reader in Biological Psychology.

In 2004 he was awarded the Society for Research on Nicotine and Tobacco Young Investigator Award, and in 2005 the European College of Neuropsychopharmacology Fellowship Award. He is currently a Deputy Editor of Nicotine and Tobacco Research and a Senior Editor of Addiction. He contributed to the recent European Commission SCENIHR Opinion on the Health Effects of Smokeless Tobacco Products.

His research interests are in the integration of multiple research perspectives to understand individual differences in smoking behaviour and, in particular, smoking cessation. This has included substantial work on smoking cessation pharmacogenetics, including analysis of the likely cost-effectiveness of personalised medicine. His research also includes the study of behavioural and neuroimaging correlates of smoking behaviour. He recently contributed material on the genetics of smoking behaviour and smoking cessation pharmacogenetics, with Caryn Lerman, to the forthcoming Surgeon General’s Report on tobacco-related disease.