Abstract 4182: Genetic associations with smoking relapse and proportion of follow-up in relapse throughout adulthood in pre- and post-menopausal women

Abstract Cigarette smoking is a major contributor to the cancer burden, so identifying genetic variants associated with smoking cessation is important for cancer prevention. Prior genetic studies of smoking cessation have been limited by short-term follow-up and not accounting for quit attempts and relapse events experienced by most smokers. In this study, candidate SNPs previously found to be associated with smoking cessation were studied in relation to smoking relapse throughout adulthood. Participants were from two, all-female longitudinal cohort studies with repeated smoking behavior measurements collected every 2 years. The study included 12,060 ever-smokers of European ancestry with genotype data who quit smoking at ≥1 timepoint. Median follow-up after first quitting smoking was 32 years. Associations between selected single nucleotide polymorphisms (SNPs) and odds of smoking relapse and, conditional on relapse, SNP associations with the proportion of follow-up in relapse were modeled using zero-inflated beta regression. Genotype by menopausal status interactions were evaluated. Women with AA genotypes for CHRNA5 SNP rs16969968 G>A or CHRNA3 SNP rs1051730 G>A (p-value = 0.04 for both) had lower odds of relapse. Among women who relapsed, those with AA genotypes for CHRNA5 SNPs rs588765 G>A or rs680244 G>A had 2.6% [95% CI 0.1 - 5.0%] and 2.4% [95% CI 0.2 - 4.9%] more follow-up in smoking relapse, respectively, compared to women with AG or GG genotypes. Women with AA or AG genotypes for DRD2 SNP rs6277 G>A had 3.3% [95% CI 0.8 - 5.7%] more follow-up in relapse than women with GG genotypes. In contrast, women with AA genotypes for COMT SNP rs4680 G>A had 2.7% [95% CI 0.2 - 5.2%] lower proportion of follow-up in relapse than women with AG or GG genotypes. These associations with the proportion of follow-up in relapse were stronger among post-menopausal women. The association of SNPs rs588765, rs680244, and rs6277 with a higher proportion of follow-up in relapse was significantly stronger among women who quit smoking post-menopause [rs588765 difference in proportion follow-up in relapse = 9.5% (95% CI 3.8 -15.2%), rs680244 difference in proportion follow-up in relapse = 10.1% (95% CI 4.4% - 15.9%), rs6277 difference in proportion follow-up in relapse = 7.6% (95% CI 1.5 - 13.6%)]. No statistically significant difference in proportion follow-up in relapse by genotype was observed among women who quit smoking prior to menopause. Several SNPs were not associated with odds of smoking relapse but, conditional on relapse, were associated with the proportion of follow-up in relapse. The findings show selected genetic variants contribute to susceptibility to smoking relapse in the long term and that the genetic risk can differ by the stage of smoking cessation. For several SNPs stronger associations were observed among post-menopausal women, indicating the importance of menopausal status. Citation Format: Stephanie K. Jones, Anthony J. Alberg, Kristin Wallace, Brett Froeliger, Matthew J. Carpenter, Bethany J. Wolf. Genetic associations with smoking relapse and proportion of follow-up in relapse throughout adulthood in pre- and post-menopausal women. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4182.