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Genetic polymorphisms of inflammatory response gene TNF-α and its influence on sporadic pancreatic neuroendocrine tumors predisposition risk

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Abstract

The diagnosed incidence of pancreatic neuroendocrine tumors (pNETs) is increasing; however, their etiology remains poorly understood. PNETs are a rare, heterogeneous group of tumors arising from the endocrine cells of the pancreas, and genetic risk factors for sporadic pNETs are inadequately understood. It is known that pNETs secrete biogenic amines, hormones and growth factors, tumor necrosis factor-a (TNF-α) being one of them. Furthermore, cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. The aim of our study was to analyze TNF-α promoter gene polymorphisms as risk factors for pNETs using germline DNA collected in a population-based case–control study of pancreatic cancer [42 pNET cases, 78 pancreatic ductal adenocarcinoma (PDAC) cases, 17 intraductal papillary mucinous neoplasm (IPMN) and 98 healthy controls] conducted in the Athens, Greece and Izmir, Turkey areas. For subsequent analysis, we excluded cases and controls with known genetic syndromes. The CC genotype at the −1031 position was more frequent in pNET and IPMN patients (p = 0.0002 and p = 0.009, respectively), suggesting its possible role in pNET development. Furthermore, the AA genotype at the −308 position was overrepresented in IPMN cases (p = 0.03), and AA genotype at the −238 position was more frequent in PDAC cases (p = 0.03) compared to healthy individuals. With regard to tumor characteristics, no statistically significant association was detected. Our findings suggest the putative role of TNF-α −1031 polymorphism in the development of pNET and IPMN, whereas the −308 polymorphism seems to be overrepresented among IPMN cases and −238 polymorphism among PDAC cases.

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Authors and Affiliations

  1. Department of General Surgery, Agia Olga Hospital, Athens, Greece

    Dimitrios Karakaxas, Christos Agalianos & Christos Dervenis

  2. Laboratory of Biology, Department of Basic Medical Science, School of Medicine, University of Athens, Michalakopoulou 176, 11527, Athens, Greece

    Maria Gazouli

  3. Department of Surgery, Faculty of Medicine, Ege University, Izmir, Turkey

    Ahmet Coker

  4. Hepatogastroenterology Unit, Second Department of Internal Medicine and Research Institute, School of Medicine, Attikon University General Hospital, University of Athens, Athens, Greece

    Ioannis S. Papanikolaou

  5. Third Department of Surgery, School of Medicine, Attikon University General Hospital, University of Athens, Athens, Greece

    Pavlos Patapis & Theodoros Liakakos

Authors
  1. Dimitrios Karakaxas
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  2. Maria Gazouli
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  3. Ahmet Coker
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  4. Christos Agalianos
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  5. Ioannis S. Papanikolaou
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  6. Pavlos Patapis
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  7. Theodoros Liakakos
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  8. Christos Dervenis
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Correspondence to Maria Gazouli.

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Karakaxas, D., Gazouli, M., Coker, A. et al. Genetic polymorphisms of inflammatory response gene TNF-α and its influence on sporadic pancreatic neuroendocrine tumors predisposition risk. Med Oncol 31, 241 (2014). https://doi.org/10.1007/s12032-014-0241-z

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  • DOI: https://doi.org/10.1007/s12032-014-0241-z

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