Review article

Etiology and Oncogenesis of Pancreatic Carcinoma

Renata Dobrila-Dintinjana ; University of Rijeka, Rijeka University Hospital Center, Department of Radiotherapy and Oncology, Rijeka, Croatia
Nenad Vanis ; University Clinical Center, Division of Gastroenterology, Sarajevo, BiH
Marijan Dintinjana ; General medicine practice »Dr. Marijan Dintinjan Office«, Rijeka, Croatia
Mladen Radić ; University of Rijeka, Rijeka University Hospital Center, Division of Gastroenterology, Department of Internal Medicine,

Abstract

Pancreatic cancer is the fourth leading cause of cancer death overall1. The factors that favor the development of pancreatic
cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a »multi-hit« hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases
the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using
pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact on carcinogenesis.

Keywords

pancreas; pancreatic carcinoma; etiology; oncogenesis; hereditary neoplastic syndromes; hereditary factors

Hrčak ID:

90991

URI

https://hrcak.srce.hr/90991

Publication date:

5.10.2012.

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