Abstract
The prevalence of head and neck cancer (HNC) and pancreatic cancer is strongly associated with major lifestyle risk factors, particularly smoking and alcohol consumption. The oral microbiome is a dynamic ecosystem susceptible to alteration by tobacco and alcohol use, resulting in dysbiosis implicated in cancer progression. While the independent effects of smoking and alcohol on oral microbial composition and their contribution to such cancer risks have been characterized, the combined influence of alcohol consumption and smoking status on shaping unique microbial signatures and the subsequent association with HNC and pancreatic cancer remains unexplored. This study investigated the interaction between alcohol consumption levels among current smokers and oral microbial diversity, and assessed the association of the resulting microbial profiles with HNC and pancreatic cancer. We used a large-scale combined dataset, encompassing alcohol, smoking and cancer status information, with oral wash samples subjected to 16s rRNA gene sequencing. We conducted analyses on alpha and beta diversity, core microbiome, indicator species, differential abundance, and potential functional pathways to identify metabolic capacities associated with lifestyle and cancer variables. Contrary to our initial prediction that alcohol use and cancer would drive distinct taxonomic signatures, our findings suggested that alcohol use and cancer status (HNC or pancreatic cancer) did not significantly shape the oral microbiome composition among current smokers, lacking unique taxonomic signatures or indicator taxa. Microbial alpha and beta diversity did not differ significantly across alcohol consumption and cancer status groups. Differential abundance analysis revealed a general downregulation of microbial species, irrespective of cancer status or alcohol use. Functional analysis using PICRUSt2 revealed virtually no differences of metabolic function due to the consumption of alcohol. Overall, the present study suggests that while alcohol consumption and HNC or pancreatic cancer does not impact the taxonomic structure of the oral microbiome among current smokers, they may induce specific functional shifts relevant to cancer progression.