Int J Clin Exp Pathol.2015 8(9):11835-11836

Oral bacteria in pancreatic cancer: mutagenesis of the p53 tumour suppressor gene

 

MESUT ÖĞRENDİK*

 *Consultant physician, Selçuk  State Hospital,  Division of Physical Medicine and Rheumatology, Selçuk, Izmir, 35920, TURKEY 

Tel.No(business): 90-232- 8927036, Tel.No(home): 90-232-4529165; Fax: 90-232-8927036; GSM Tel. No: 90-554-9329356; E-mail: mogrendik@gmail.com

  

Abstract

Pancreatic cancer is the fourth-leading cause of cancer-related deaths worldwide. Chronic pancreatitis is frequently observed in patients with pancreatic cancer, and a significant relationship between orodigestive cancer-related deaths and chronic periodontitis has been detected. Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, collectively called the Red complex, are the major pathogens responsible for chronic periodontitis and secrete peptidylarginase deiminase (PAD). Michaud et al. detected higher levels of antibodies formed against P. gingivalis in patients with pancreatic cancer than healthy volunteers. High rates of tumor-suppressor gene p53 mutations, particularly p53 arginine mutations, were detected in pancreatic cancer patients. K-ras codon 12 arginine mutations were detected in pancreatic cancer patients in a 1985 study and have been observed in other studies. Oral bacteria PADs might lead to p53 and K-ras point mutations by degrading arginine.

KEYWORDS: Pancreatic cancer; arginine; oral bacteria; p53 mutation

PMID: 26617937

 

Supplement      

Pancreatic cancer is the fourth-leading cause of cancer-related deaths worldwide and causes approximately 8,000 deaths in the United Kingdom every year. The rate of this cancer has been increasing in western countries. Chronic pancreatitis is frequently observed in patients with pancreatic cancer, and a significant relationship between orodigestive cancer-related deaths and chronic periodontitis has been detected. This article examines the association between oral bacteria and the etiology of pancreatic cancer.

Periodontal diseases are a group of disorders that affect the supporting tissues of the teeth. Periodontal diseases are common; for example, in a national survey in the United Kingdom, 79% of dentate adults had bleeding gums, 88% had calculus, and 69% had periodontal pockets, including 10% with deep pockets.

In periodontal diseases, the junctional epithelial tissue at the base of the gingival crevice migrates down the root of the tooth to form a periodontal pocket. This movement is as a direct result of the microorganisms themselves and the indirect but potentially damaging side-effects of the host’s inflammatory response to plaque accumulation. Individuals with periodontal disease have different predominant microflora than healthy individuals, but there is no single or unique pathogen associated with the diseases. Most are Gram-negative and obligately anaerobic, except for capnophilic microflora which are associated with localized juvenile periodontitis. Although the microflora in periodontal disease are diverse, certain species are commonly found at sites undergoing tissue breakdown, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Prevotella intermedia, and Treponema denticola.

Among the Gram-negative bacteria isolated in high numbers from sites affected by periodontal disease, P. gingivalis has been shown to have the greatest proteolytic activity and to be the most virulent species inoculated in animals in a simple pathogenicity test. The majority of this proteolytic activity has been characterized as gingipain, an arginine-specific, cysteine protease. P. gingivalis, T. forsythia, and T. denticola, collectively called the Red complex, are the major pathogens responsible for chronic periodontitis and secrete peptidylarginase deiminase (PAD).

In a study, Michaud et al. detected higher levels of antibodies formed against P. gingivalis in patients with pancreatic cancer than healthy volunteers (2). This multicenter study involved 405 pancreatic cancer patients.

High rates of tumor-suppressor gene p53 mutations, particularly p53 arginine mutations, were detected in pancreatic cancer patients. There is a close relationship between p53ArgPro mutations and gastrointestinal cancers, including pancreatic cancer.

K-ras codon 12 arginine mutations were detected in pancreatic cancer patients in a 1985 study and have been observed in other studies. Point mutations at codon 12 of the K-ras gene have been observed in more than 75% of pancreatic cancer patients. These mutations are considered a sign of poor prognosis. The GTPase-activating protein arginine finger is crucial for the interaction of Ras. Oral bacteria PADs might lead to p53 and K-ras point mutations by degrading arginine.

The Importance of this hypothesis

Oral bacteria may be pancreatic-cancer-causing agents.

 

References

  1. Ogrendik M 2015 Oral bacteria in pancreatic cancer: mutagenesis of the p53 tumour suppressor gene. Int J Clin Exp Pathol 8:11835-11836.
  2. 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, Palli D, Tumino R, Panico S, Siersema PD, Peeters PH, Lund E, Barricarte A, Huerta JM, Molina-Montes E, Dorronsoro M, Quirós JR, Duell EJ, Ye W, Sund M, Lindkvist B, Johansen D, Khaw KT, Wareham N,Travis RC, Vineis P, Bueno-de-Mesquita HB, Riboli E 2013 Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut 62:1764-70

 

 

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