Abstract B54: A candidate gene study of smoking cessation

Background: Efforts to identify genes that influence smoking cessation have been largely unsuccessful to date. However, SNPs in the chromosome 15q25 region that encodes the nicotinic receptor subunits CHRNA5, CHRNA3, and CHRNB4 have been consistently and strongly associated with nicotine dependence as measured directly through dependence surveys or indirectly with smoking quantity (cigarettes per day, cpd). These SNPs have been found to either be modestly or not at all associated with smoking cessation as defined by a variety of different phenotypes. Despite the fact that nicotine dependence influences smoking cessation, these results suggest that cessation may be influenced by a wider range of genetic variants than just those that influence measures of nicotine dependence. Methods: To identify genes important for smoking cessation, we defined a smoking cessation phenotype based on number of quit attempts; easy quitters achieved successful, long-term (> 1 year) abstinence after their first quit attempt and difficult quitters reported ≥10 attempts before either continuing to smoke or quitting. We identified 1,500 easy quitters and 1,500 difficult quitters who were participants in the Cancer Prevention Study-3 (CPS-3), a large prospective study of cancer incidence and mortality conducted by the American Cancer Society. The association of 83 SNPs from 25 nicotine signaling and metabolism genes that had previously been associated with some aspect of smoking behavior with difficulty quitting was determined using logistic regression. Results: Three SNPs in three separate genes were significantly associated with difficult quitting (p Conclusions: Although none of the SNPs investigated were statistically significantly associated with the number of quit attempts, these results suggest that examining this phenotype in future genome-wide association studies would be useful for the discovery of genes that could be targeted for the development of novel smoking cessation aids. Citation Format: Victoria L. Stevens, Susan M. Gapstur, Juzhong Sun, Eric J. Jacobs, Mia M. Gaudet, J. Lee Westmaas, Alpa V. Patel. A candidate gene study of smoking cessation. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B54.