Investigators have found several oral bacteria and fungi associated with an increased risk for pancreatic cancer, according to findings published in JAMA Oncology. This cohort study seems to confirm a long-standing suspicion of the relationship between poor oral health and pancreatic cancer and suggests that oral microbiota could be used as biomarkers to identify patients at higher risk for pancreatic cancer who could benefit from screening and prevention measures.
“Our findings provide new insight into the relationship between the oral microbiome and pancreatic cancer,” said lead study author Yixuan Meng, PhD, Postdoctoral Fellow in the Department of Population Health at NYU Grossman School of Medicine.
“It is clearer than ever that brushing and flossing your teeth may not only help prevent periodontal disease but may also protect against cancer,” added co-senior study author Richard Hayes, DDS, MPH, PhD, Professor in the Department of Population Health at NYU Grossman School of Medicine.
Study Rationale and Methods
The oral microbiome is increasingly being studied for its role in human health and to understand its relationship with cancer risk as well as treatment response. Experts have previously observed that those with poor oral health are more vulnerable to developing pancreatic cancer than those with better oral health, but prior research was limited to 16S amplicon sequencing as well as that of smaller retrospective case-control studies.
The research team previously conducted a small study showing a connection between oral microbes and pancreatic cancer, but they were unable to show which species were related.
Meng et al conducted a cohort study using data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, totaling 122,000 cohort participants. After enrollment, patients rinsed with mouthwash and provided oral samples to test for microbes. These patients were followed for about 9 years to determine which patients developed pancreatic cancer to compare microbes between patients with pancreatic cancer and individuals without.
At a median follow-up of 8.8 years (interquartile range, 4.9‒13.4 years), 445 cohort participants with available samples developed pancreatic cancer. They were matched with 445 controls without cancer.
The oral bacterial microbiome was characterized with whole-genome shotgun sequencing, and the fungal microbiome was analyzed with internal transcribed spacer sequencing. Their association with pancreatic cancer was assessed using Analysis of Compositions of Microbiomes With Bias Correction 2. Additionally, microbial risk scores were calculated for the development of pancreatic cancer from the risk-associated species.
Key Findings
The researchers found that Porphyromonas gingivalis, Eubacterium nodatum, and Parvimonas micra oral bacteria were all associated with an increased risk for developing pancreatic cancer. A bacteriome-wide scan found that 8 oral bacteria were associated with a decreased risk for developing pancreatic cancer, whereas 13 oral bacteria were associated with an increased risk. The false discovery rate‒adjusted Q statistic was less than 0.05. For oral fungi, the genus Candida led to an increased risk of pancreatic cancer development.
Among a total 27 oral species, the microbial risk score was associated with an increased pancreatic cancer risk, with a multivariate odds ratio per 1-SD increase in microbial risk score of 3.44 (95% confidence interval = 2.63‒4.51).
“By profiling bacterial and fungal populations in the mouth, oncologists may be able to flag those most in need of pancreatic cancer screening,” said co-senior study author Jiyoung Ahn, PhD, Professor in the Departments of Population Health and Medicine at NYU Grossman School of Medicine and Associate Director for Population Sciences at Perlmutter Cancer Center.
The study authors next plan to investigate how the oral microbiome may impact patient survival.
Disclosure: Research funding was provided by National Institutes of Health grants. For full disclosures of the study authors, visit jamanetwork.com.