Background: 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 peptidylarginine deiminase. Anti-P. gingivalis antibodies titers are higher in pancreatic cancer patients than in healthy subjects. Summary: This review examines the association between oral bacteria and the etiology of pancreatic cancer. Key Message: High rates of tumor suppressor gene p53 mutations, particularly p53 arginine mutations, were detected in pancreatic cancer patients. K-ras arginine mutations were detected in patients with pancreatic cancer. Oral bacteria peptidylarginine deiminases might lead to the p53 and K-ras point mutations by degrading arginine. Practical Implications: Oral bacteria are likely to be responsible for the development of pancreatic cancer. If this hypothesis is true, it may reveal the real cause of pancreatic cancer, which is a fatal disease.

Keywords:
Etiology, Pancreatic cancer, Periodontal pathogens
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
2.
Office for National Statistics: Cancer Statistics Registrations Series MB1. London, Office for National Statistics, 2011.
3.
Boyle P, Hsieh CC, Maisonneuve P, La Vecchia C, Macfarlane GJ, Walker AM, Trichopoulos D: Epidemiology of pancreas cancer (1988). Int J Pancreatol 1989;5:327-346.
4.
Michaud DS: Role of bacterial infections in pancreatic cancer. Carcinogenesis 2013;34:2193-2197.
5.
Ahn J, Segers S, Hayes RB: Periodontal disease, Porphyromonas gingivalis serum antibody levels and orodigestive cancer mortality. Carcinogenesis 2012;33:1055-1058.
6.
Marsh PD, Martin MV (eds): Oral Microbiology, ed 4. Bodmin, MPG Books Ltd, 2001.
7.
Binder Gallimidi A, Fischman S, Revach B, Bulvik R, Maliutina A, Rubinstein AM, Nussbaum G, Elkin M: Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget 2015;6:22613-22623.
8.
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: Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut 2013;62:1764-1770.
9.
Barton CM, Staddon SL, Hughes CM, Hall PA, O'Sullivan C, Klöppel G, Theis B, Russell RC, Neoptolemos J, Williamson RC, et al: Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. Br J Cancer 1991;64:1076-1082.
10.
Liu L, Wang K, Zhu ZM, Shao JH: Associations between P53 Arg72Pro and development of digestive tract cancers: a meta-analysis. Arch Med Res 2011;42:60-69.
11.
Prassolov VS, Sakamoto H, Nishimura S, Terada M, Sugimura T: Activation of c-Ki-ras gene in human pancreatic cancer. Jpn J Cancer Res 1985;76:792-795.
12.
Evans T, Faircloth M, Deery A, Thomas V, Turner A, Dalgleish A: Analysis of K-ras gene mutations in human pancreatic cancer cell lines and in bile samples from patients with pancreatic and biliary cancers. Oncol Rep 1997;4:1373-1381.
13.
Watanabe H, Miyagi C, Yamaguchi Y, Satomura Y, Ohta H, Motoo Y, Okai T, Yoshimura T, Tsuji Y, Sawabu N: Detection of K-ras point mutations at codon 12 in pancreatic juice for the diagnosis of pancreatic cancer by hybridization protection assay: a simple method for the determination of the types of point mutation. Jpn J Cancer Res 1996;87:466-474.
14.
Sinn BV, Striefler JK, Rudl MA, Lehmann A, Bahra M, Denkert C, Sinn M, Stieler J, Klauschen F, Budczies J, Weichert W, Stenzinger A, Kamphues C, Dietel M, Riess H: KRAS mutations in codon 12 or 13 are associated with worse prognosis in pancreatic ductal adenocarcinoma. Pancreas 2014;43:578-583.
15.
Prior IA, Lewis PD, Mattos C: A comprehensive survey of Ras mutations in cancer. Cancer Res 2012;72:2457-2467.
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2016
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