Pancreatic Cancer and Oral Microbiome

Pancreatic Cancer Clinical Trial

Official title:

Pancreatic canceR pErioDontAl sTatus and Oral micRobiome - PREDATOR Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04993846
• Other study ID #: 3292CESC
• Status: Recruiting
• Start date: July 26, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2021
• Source: Azienda Ospedaliera Universitaria Integrata Verona
• Contact: Salvatore Paiella, MD, PhD
• Phone: 00390458126009
• Email: salvatore.paiella[@]univr.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18-75 years;
• The ability of the subject to understand the character and individual consequences of the clinical trial
• Written informed consent

Exclusion Criteria:

• A recent history of antibiotics (< 4 weeks before the enrolment)
• Current systemic or topic medication with steroids
• Active smoking or alcohol habits
• Vegan diet or dietary disorders (anorexia, bulimia)
• Immune system disorders
• Diabetes
• Obesity (defined as having a BMI > 30)
• Other current malignancies
• History of gastrointestinal tract resections, chronic gastrointestinal diseases (es. Inflammatory bowel diseases, or gastroesophageal reflux disease)
• Pregnant or breastfeeding patients
• Impaired mental state or language problems

Related Conditions & MeSH terms

• IPMN
• Oral Microbiome
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Diagnostic Test:
• Dental plaque sampling
Dental plaque sampling
• qPCR
qPCR

Locations

Country	Name	City	State
Italy	General and Pancreatic Surgery Unit	Verona
Italy	Section of Dentistry and Maxillofacial Surgery, Department of Surgical Sciences, Paediatrics and Gynaecology	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Integrata Verona

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, Miller G, Ravel J, Hayes RB, Ahn J. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. — View Citation

Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K, Wong DT. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut. 2012 Apr;61(4):582-8. doi: 10.1136/gutjnl-2011-300784. Epub 2 — View Citation

Michaud DS, Izard J, Wilhelm-Benartzi CS, You DH, Grote VA, Tjønneland A, Dahm CC, Overvad K, Jenab M, Fedirko V, Boutron-Ruault MC, Clavel-Chapelon F, Racine A, Kaaks R, Boeing H, Foerster J, Trichopoulou A, Lagiou P, Trichopoulos D, Sacerdote C, Sieri S — View Citation

Olson SH, Satagopan J, Xu Y, Ling L, Leong S, Orlow I, Saldia A, Li P, Nunes P, Madonia V, Allen PJ, O'Reilly E, Pamer E, Kurtz RC. The oral microbiota in patients with pancreatic cancer, patients with IPMNs, and controls: a pilot study. Cancer Causes Con — View Citation

Torres PJ, Fletcher EM, Gibbons SM, Bouvet M, Doran KS, Kelley ST. Characterization of the salivary microbiome in patients with pancreatic cancer. PeerJ. 2015 Nov 5;3:e1373. doi: 10.7717/peerj.1373. eCollection 2015. — View Citation

Vogtmann E, Han Y, Caporaso JG, Bokulich N, Mohamadkhani A, Moayyedkazemi A, Hua X, Kamangar F, Wan Y, Suman S, Zhu B, Hutchinson A, Dagnall C, Jones K, Hicks B, Shi J, Malekzadeh R, Abnet CC, Pourshams A. Oral microbial community composition is associate — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Qualitative analysis of the dental plaque microbiome in patients with pancreatic cancer vs. healthy controls and IPMN patients	Whole-Genome Sequencing analysis	Baseline (At enrollment)
Primary	Correlation analysis between periodontal status and dental plaque microbiome	According to the periodontal status (appropriate scores will be used), patients will be divided into distinct groups. The proportional means of abundance of selected genera and species, and bacterial load (real-time data) between these groups will be analyzed using the Mann-Whitney U-test. Correlations between mean distributions of the genera and species and the parodontal status scores values will be analysed using the Spearman Correlation Coefficient.	Baseline (At enrollment)
Primary	Quantitative analysis of the dental plaque microbiome in patients with pancreatic cancer vs. healthy controls and IPMN patients	Whole-Genome Sequencing analysis	Baseline (At enrollment)
Secondary	Qualitative analysis of OM and periodontal status between the various stages of PC	Whole-Genome Sequencing analysis	Baseline (At enrollment)