Genome-Wide Association for Smoking Cessation Success: Participants in the Patch in Practice Trial of Nicotine Replacement

Abstract

Aims: To confirm and extend to primary care settings prior genome-wide association results that distinguish smokers who successfully quit from individuals who were not able to quit smoking in clinical trials. Materials & methods: Affymetrix^® 6.0 Arrays were used to study DNA from successful quitters and matched individuals who did not quit from the Patch in Practice study of 925 smokers in 26 UK general practices who were provided with 15 mg/16 h nicotine-replacement therapy and varying degrees of behavioral support. Results: Only a few SNPs provided results near ‘genome-wide‘ levels of significance. Nominally significant (p < 0.01) SNP results identify the same chromosomal regions identified by prior genome-wide association studies to a much greater extent than expected by chance. Conclusion: Ability to change smoking behavior in a general practice setting appears to share substantial underlying genetics with the ability to change this behavior in clinical trials, though the modest sample sizes available for these studies provides some caution to these conclusions.

KEYWORDS::

• DNA microarray
• genetic susceptibility
• nicotine dependence
• nicotine replacement
• smoking cessation

Acknowledgments

We are grateful for the thoughtful advice and discussion from Jed Rose, Dean Hamer, Caryn Lerman, Ray Niaura and Sean David. We would also like to thank all participants in the Patch in Practice trial as well as all clinical and laboratory staff who worked on the trial. We would like to acknowledge excellent technical assistance by Dr Qing Rong Liu.

Financial & competing interests disclosure

Dr George R Uhl is listed as an inventor for a patent application filed by Duke University (NC, USA) based on genomic markers that distinguish successful quitters from unsuccessful quitters in data from other clinical trials. This research was supported by the NIH Intramural Research Program, NIDA, DHSS and a Cancer Research UK Programme Grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

Dr George R Uhl is listed as an inventor for a patent application filed by Duke University (NC, USA) based on genomic markers that distinguish successful quitters from unsuccessful quitters in data from other clinical trials. This research was supported by the NIH Intramural Research Program, NIDA, DHSS and a Cancer Research UK Programme Grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.