The association between periodontal disease and pancreatic cancer: epidemiology, mechanisms, and implications for clinical management

Pancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma (PDAC), is a highly lethal malignant tumor with poor prognosis, limited early screening strategies, and high chemoresistance. Periodontal disease (PD), a prevalent chronic inflammatory disorder caused by oral microbiota dysbiosis, has been increasingly linked to systemic diseases, including cancer. This review summarizes the epidemiological evidence, potential pathogenic mechanisms, and clinical management implications of the association between PD and PC. Epidemiological studies, including meta-analyses, cohort studies, and case-control studies, consistently demonstrate that PD (especially moderate-to-severe periodontitis and combined gingivitis-periodontitis) is associated with an increased risk of PC incidence and mortality, with significant population heterogeneity (more prominent in middle-aged and elderly individuals, males, and those with comorbid diabetes). Specific periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, play key roles in this association, showing dose-response relationships and preceding PC onset. Mechanistically, PD contributes to PC development through multiple interconnected pathways: translocation and colonization of periodontal pathogens in pancreatic tissue, induction of precancerous lesions (e.g., acinar-to-ductal metaplasia), activation of inflammatory signaling pathways (TLR4/NF-κB, Wnt/β-catenin), immune dysregulation and tumor immune escape, microbiota imbalance and carcinogenic metabolite accumulation (e.g., acetaldehyde, nitrosamines), and induction of chemoresistance (via cytidine deaminase-mediated gemcitabine inactivation or Notch1 pathway activation). Clinically, this association provides novel perspectives for PC prevention and management: integrating periodontal health assessment into PC risk screening, developing non-invasive diagnostic biomarkers (oral microbiota, miRNAs, saliva metabolites), optimizing treatment strategies (targeted antibiotics, probiotics, phage therapy), and establishing a multidisciplinary collaboration (MDT) model involving dentistry, oncology, gastroenterology, and microbiology. In conclusion, PD is a potentially modifiable risk factor for PC, and oral health management may serve as a cost-effective strategy for PC prevention and improved prognosis. Future prospective studies are needed to confirm the causal relationship and standardize clinical practices for this cross-organ association.