Pancreatic Cancer and Oral Microbiome

Summary

Pancreatic cancer (PC) is a solid malignancy with a dismal prognosis. It has a 5-year survival rate of approximately 8%. This is due to the usually late diagnosis, to chemoresistance, and to intrinsic biological aggressiveness. Risk factors for PC are smoking, alcohol, chronic pancreatitis, obesity, and diabetes. Recently, research has been dedicated to the identification of a causal connection between certain pathogenic microorganisms, especially of the oral flora, and PC. This would ultimately allow to identify new biomarkers to adopt for early diagnosis, or to create new strategies for prevention.

Oral microbiota, periodontal disease and neoplastic risk

When referring to "oral microbiota" (OM), about 700 hundreds bacterial species are mentioned, colonizing the oral cavity. A change in the normal flora of the oral cavity is commonly indicated with the term "dysbiosis".

The causal connection between oral microbiota, periodontal disease and neoplastic risk is possibly triple. First, it has been found that oral flora substantially differentiates between cancer patients and controls. In particular, the most predominant phyla in cancer patients are Firmicutes and Actinobacteria, whereas Proteobacteria, Fusobacteria, and Bacteroides are more common in healthy controls. This highlights the possibility of a direct causal connection between dysbiosis and neoplastic risk. Second, oral dysbiosis represents the main risk factor of PD that per sé is a risk factor of many cancers. Third, the conditions leading to oral dysbiosis (alcohol, smoking, obesity, diabetes, chronic drugs intake, dietary habits, etc.) are the most well known risk factors either for cancer and oral dysbiosis. The common denominator is always represented by chronic inflammation and migration of microorganisms to distant sites, ultimately promoting neoplastic progression.

This tangled net of causal connections sheds light on the potential important role of the oral cavity and PD as independent risk factors for many cancers, and as modifiable elements to reduce the neoplastic risk and to perform prevention(15).

Oral microbiota, periodontal disease and pancreatic cancer

In 2012, the pioneering study by Farrell et al. showed that bacteria of the OM can discriminate PC patients from healthy subjects. Since then, few other studies have shown that changes of the OM are independent risk factors for PC and that the OM of PC patients differs than controls. The involved bacterial species are many and their role seems to be contrasting on the basis of the study considered. Farrell et al. found that the combined adoption of Neisseria elongata and Streptococcus mitis distinguished PC patients from healthy controls (both showed low levels in PC patients, AUC of combined sensitivity 0.9), and that higher levels of Granulicatella adiacens and Streptococcus Mitis distinguished PC patients from chronic pancreatitis ones. Torres et al. found a higher ratio of Leptotrichia to Porphyromonas in PC patients. Fan et al. reported that Porphyromonas gingivalis, Prevotella intermedia, Alloprevotella and Aggregatibacter actinomycetemcomitans are associated with a higher risk of PC, whereas Fusobacteria and Leptotrichia were associated with a decreased risk. Another study evaluating the diversity of OM in three groups of individuals (PC patients, patients suffering from Intraductal papillary mucinous neoplasms \[a pancreatic preneoplastic condition\], and healthy controls), excluding current smokers and users of antibiotics, found no differences in the OM, although patients with PC had a higher proportion of Firmicutes compared with Intraductal Papillary Mucinous Neoplasms (IPMNs) and controls. Lastly, a recent study by Gaiser et al. showed that the cystic fluid of patients submitted to surgery for IPMNs contained bacterial species that are commonly found in the oral cavity, including, among the others, Granulicatella adiacens, Fusobacterium nucleatum. These two, in particular, were higher in the cohort of individuals with IPMNs with high-grade dysplasia, indicating a pivotal role in tumorigenesis(19).

As regards PD, the first studies demonstrating an association between PD and PC date back to the mid of 2000's, and they were confirmed afterward, even adjusting confounders such as diabetes, pancreatitis, hyperlipemia, smoking or alcohol-related conditions. PD is strictly connected to oral hygiene, that seems to be associated to an increased risk of PC. It is now clear that PD can concur to development of PC in several ways, promoting chronic inflammation, spreading continuously to distant organs (including pancreas) pro-tumorigenic bacteria, or promoting a chronic alteration of the immune function that make the individual more prone to develop a cancer.

Conditions

• Oral Microbiome
• Pancreatic Cancer
• IPMN
• Parodontopathy

Interventions

DIAGNOSTIC_TEST

Dental plaque sampling

Dental plaque sampling

DIAGNOSTIC_TEST

qPCR

qPCR

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona

  lead OTHER

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-07-26

Primary Completion

2023-06-30

Completion

2023-12-31

Countries

• Italy

Study Locations