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Association of COMT Val^108/158Met Genotype with Smoking Cessation in a Nicotine Replacement Therapy Randomized Trial

¹ Department of Clinical Pharmacology and ² Childhood Cancer Research Group, University of Oxford, Oxford, United Kingdom; ³ The Warren Alpert Medical School of Brown Medical School and Memorial Hospital of Rhode Island, Rhode Island; ⁴ Medical Research Council Laboratories, Banjul, Gambia; and ⁵ Department of Experimental Psychology, University of Bristol, Bristol, United Kingdom

Requests for reprints: Marcus R. Munafò, Department of Experimental Psychology, University of Bristol, 12a Priory Road, Bristol BS8 1TU, United Kingdom. Phone: 44-117-9546841; Fax: 44-117-9288588. E-mail: marcus.munafo{at}bristol.ac.uk

We investigated the association of catechol O-methyltransferase (COMT) genotype with abstinence following a smoking cessation attempt among a large cohort of smokers who attempted to quit using either the nicotine transdermal patch or placebo and were followed up over an 8-year period following their initial cessation attempt. In addition, we examined the possible moderating influence of sex on any association. The genotype x treatment interaction effect at 12-week follow-up indicated a greater benefit of active nicotine replacement treatment compared with placebo on likelihood of abstinence in the COMT Met/Met genotype group (33% versus 12%), in comparison to the Met/Val + Val/Val group (22% versus 16%). Our results indicate that COMT genotype may moderate the effect of active transdermal nicotine patch compared with placebo, with reduced relative benefit of nicotine replacement therapy in individuals with Met/Val or Val/Val genotype. Our data follow an emerging pattern of results suggesting that genetic variation in the dopamine pathway may provide a future basis for tailored smoking cessation therapies, but indicate that different genes influencing various components of this pathway may have different effects on response to smoking cessation pharmacotherapy. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1065–9)

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