Abstract C030: Relationship between the oral microbiome and tobacco-induced DNA damage in African American and White persons who smoke

Abstract

Abstract Exposure to tobacco smoke chemicals and toxicants may cause unique changes to an individual’s oral microbiome, impacting immuno-inflammatory responses, the metabolism of tobacco smoke carcinogens, and overall health status. In our previous study, HPB-releasing DNA adducts (DNA damage derived from tobacco-specific nitrosamines) were higher in oral cells of African American (AA, n=75) when compared to White (WH, n=71) persons who smoke, even after adjusting for key confounders such as smoking dose. In this study, we examined the relationship between the levels of HPB-releasing DNA adducts and microbiome composition in these individuals. 16S rRNA gene sequencing, targeting the V4 hypervariable region, was performed on DNA isolated from mouthwash samples. Sequences were clustered into Amplicon Sequence Variants (ASV) using QIIME, and metagenomic content was inferred using PICRUSt. Our results showed a significant difference in alpha-diversity metrics: observed richness and Shannon indexes (Kruskal-Wallis test, H = 8.42, p <0.01 and H = 6.85, p <0.03, respectively) across levels of DNA damage (low, intermediate, and high). Post hoc tests with pairwise comparisons showed that, for both indexes, individuals with high levels of HPB-releasing DNA adducts had significantly lower alpha diversity than those with intermediate levels (p <0.05). However, there were no differences in beta diversity as measured by Bray-Curtis (R2 = 1.15, p = 0.2) and Jaccard (R2 = 1.1, p = 0.1) indices across individuals with different levels of HPB-releasing DNA adducts. Multivariable association tests revealed that high levels of the DNA adducts were positively associated with Enterobacteriaceae, while intermediate levels were associated with Porphyromonas endodontalis, Prevotella spp, Neisseria spp, Actinomyces spp, and Fusobacterium. In addition, predicted functional profiling showed that intermediate levels of HPB-releasing DNA adducts were positively associated with amino acid, carbohydrate, and hem biosynthesis, along with reductive tricarboxylic acid cycle and formaldehyde degradation pathways. Comparisons between AA and WH persons who smoke showed that AA had significantly higher alpha diversity as assessed by observed bacterial richness and The Shannon index (Wilcoxon rank-sum tests, q-value=0.03 and 0.004, respectively). Differences between AA and WH were also found for beta diversity (Bray-Curtis: R2=2.4, p=0.01, Jaccard: R2=1.9, p=0.01, weighted Unifrac R2=0.02 p=0.007). The abundance of taxa associated with intermediate levels of DNA damage (Prevotella spp, Neisseria spp, Actinomyces spp, Fusobacterium) was also higher in AA persons who smoke. Together, our findings suggest that certain compositional and functional characteristics of the oral microbiome may serve as indicators of macromolecular responses to harmful chemical exposures from tobacco. The potential mechanistic contribution of the oral microbiome to such responses and its potential role in the observed racial/ethnic differences in cancer risk due to smoking should be further investigated. Citation Format: Aleksandra Alcheva. Relationship between the oral microbiome and tobacco-induced DNA damage in African American and White persons who smoke [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C030.