Abstract 2760: Nicotinic acetylcholine receptor SNPs are associated with smoking cessation
Authors: Asomaning Kofi , Heist Rebecca , Zhai Rihong , Sheu Chau-Chyun , Chen Feng , Liu Geoffrey , Su Li , Lin Xihong , De Vivo Immaculata , Christiani David C. 
Published: June 2012

Introduction: Several genes have been linked with smoking behavior, and recent findings from candidate gene and genome wide association studies (GWAS) point to an area on Chr15q24-25.1 as a plausible site. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Consistent results have been reported for cigarettes smoked per day (CPD), but data for smoking initiation, duration and cessation remain mixed. In this study, we assessed the relationship between the two most significant and consistently reported single nucleotide polymorphisms (SNPs), rs1051730 and rs8034191 and various smoking phenotypes.

Methods: From a large ongoing case-control study of the molecular epidemiology of lung cancer, which began in 1992 at the Massachusetts General Hospital, we derived this study population of controls only (i.e., no diagnosis of lung cancer). The polymorphisms were genotyped by the 5’ nuclease assay (Taqman) using the ABI Prism 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA). Interviewer-administered questionnaires collected information on demographics, and detailed smoking histories from each subject. We log transformed all the continuous smoking phenotype variables. Multiple linear regression models were used to assess the association between SNPs and continuous outcomes and estimates for the association with binary outcomes were obtained from logistic regression. We used the additive genetic model for individual SNPs, controlling for age, gender and college education.

Results: There were 1452 subjects. There were statistically significant differences in age, gender, and college education between never, former and current smokers. Never smokers were excluded in the comparison of smoking variables. Age of smoking initiation and smoking duration differed significantly between former and current smokers. There was no significant difference between genotypes of rs1051730 except by smoking status (never, former, current). The proportion of never smokers was much higher in the wildtype group compared to heterozygous and homozygous variant group.

The association of smoking cessation (current vs. former smokers) with rs1051730, adjusted for age, gender and college education was statistically significant (p=0.05). Results for the other smoking phenotype included smoking initiation (never vs. ever smokers) (P=0.62), age of smoking initiation (P=0.83), smoking duration (P=0.76), CPD (0.08), and number of year of smoking cessation (0.36). We obtained similar results for SNP rs8034191.

Conclusion In conclusion, we have shown an association between rs1051730 and smoking cessation. We also replicated previous findings for intensity (CPD). If confirmed in future studies, these findings may provide a role for genetic screening in smoking cessations programs.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2760. doi:10.1158/1538-7445.AM2011-2760