Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Important advances in the understanding of pancreatic diseases have taken place through the application of molecular methods in the study of the inherited form of pancreatitis and pancreas cancer. Mutations of the cationic trypsinogen gene have been found to be causative for hereditary pancreatitis with important implications for the molecular pathogenesis of acute and chronic pancreatitis. A variety of cancer syndromes involving the P16 and BRCA2 genes, for example, also lead to pancreatic cancer, but the gene responsible for familial pancreatic cancer has not been identified so far. The establishment of a European Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC) will facilitate future developments.
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PMID:Hereditary pancreatitis and familial pancreatic cancer. 943 3

Premalignant conditions of the pancreas include benign tumours of the pancreas, intraepithelial neoplasia arising within pancreatic ducts, and tumours of the neuroendocrine cells of the pancreas. In addition, there is a variety of rare genetic conditions that predispose to pancreatic exocrine malignancies such as Peutz-Jeghers syndrome, hereditary non-polyposis colorectal cancer syndrome, familial pancreatitis, germline BRCA2 mutations, and pancreatic endocrine malignancies such as type 1 neurofibromatosis (von Recklinghausen's disease) and multiple endocrine neoplasia type 1. More controversial is the concept of chronic pancreatitis and diabetes mellitus as conditions that increase the risk of pancreatic cancer. However, there is no doubt that smoking is a potentiating factor for pancreatic cancer, especially in people who have familial/genetic risk factors. This review will include the recently proposed new nomenclature and classification system for intraepithelial neoplasia in the pancreatic ducts, an overview of the various familial syndromes that are associated with an increased risk of pancreatic tumours, the surveillance programmes that have been introduced to monitor such families, and methods for early diagnosis.
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PMID:Premalignant conditions of the pancreas. 1255 88

This paper overviewed risk factors of pancreatic cancer. Both genetic and environmental factors may be playing significant roles in the development of pancreatic cancer. Cigarette smoking has been established as a major risk factor for pancreatic cancer, based on findings from almost all epidemiological studies. Long-term smoking cessation may reduce the risk. The evidence that alcohol drinking and coffee consumption increase the risk is not sufficient, although an association with higher level of consumption remains a possibility. Diabetes mellitus, long-standing diabetes in particular, may be a risk factor for pancreatic cancer. Individuals with hereditary pancreatitis or non-hereditary chronic pancreatitis are possibly at increased risk of pancreatic cancer. Higher intake of meat and fat may be associated with an increased risk, while consumption of fruits/vegetables appears to have a protective effect. Individuals with mutations or deletion in such genes as K-ras, p16, p53, DPC4, and BRCA2 increased the risk of developing pancreatic cancer. Cigarette smoking may play a role in the development of these mutations.
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PMID:An Epidemiological Overview of Environmental and Genetic Risk Factors of Pancreatic Cancer. 1271 18

In the United States, pancreatic cancer is the fourth most frequent cause of cancer death in males as well as females, after lung, prostate or breast, and colorectal cancer. Each year, approximately 30 000 Americans are diagnosed with pancreatic cancer and about the same number die of it. Germline mutations in a few genes including p16 and BRCA2 have been implicated in a small fraction of cases, as has chronic pancreatitis. The one established risk factor for pancreatic cancer is cigarette smoking: current smokers have two to three times the risk of nonsmokers. Studies of dietary factors have not been entirely consistent but do suggest associations of higher risk with consumption of smoked or processed meats or with animal foods in general and lower risk with consumption of fruits and vegetables. Colonization by Helicobacter pylori appears to increase risk, and a history of diabetes mellitus may also increase risk. The purpose of this epidemiologic review is to consider the possibility that risk of pancreatic cancer is increased by factors associated with pancreatic N-nitrosamine or N-nitrosamide exposures and with chronic excess gastric or duodenal acidity. Host genetic variation in inflammatory cytokine mechanisms may also be involved in this process. Many features of the evidence bearing on the pathophysiology of pancreatic cancer appear to support connections with N-nitroso compounds and with gastric acidity.
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PMID:Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. 1470 43

Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer.
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PMID:[The epidemiology of pancreatic cancer]. 2096 43

Pancreatic cancer is the fourth leading cause of cancer death overall. 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.
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PMID:Etiology and oncogenesis of pancreatic carcinoma. 2321 74

Pancreatic ductal adenocarcinoma (PDAC) represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60-80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5). In contrast R0 resection shows the survival 18-27 months. Laboratory and imaging screening methods are not indicated on large scale. Risk factors are smoking, alcohol abuse, chronic pancreatitis, diabetes mellitus. Genetic background in most PDAC has not been detected yet. Some genes connected with high risk of PDAC (e.g. BRCA2, PALB2) have been identified as significant and highly penetrative, but link between PDAC and these genes can be seen only in 10-20%. This article surveys perspective oncogenes, tumour suppressor genes, microRNA. Albeit CT is still favoured over other imaging methods, involvement of NMR rises. Surgery prefers the "vessel first" approach, which proves to be justified especially in R0 resection. According to EBM immunotherapy same as radiotherapy are not significant in PDAC treatment. Chemotherapy shows limited importance in conversion treatment of locally advanced or borderline tumours or in case of metastatic spread. Unified procedures cannot be defined due to inhomogenous arrays. Surgical resection is the only chance for curative treatment of PDAC and depends mainly on timely indication for surgery and quality of multidisciplinary team in a high-volume centre.
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PMID:Pancreatic Cancer Diagnostics and Treatment--Current State. 2665 99

Clinicopathologic and genetic features of familial pancreatic cancer (FPC) in Asian countries remain largely unknown. The main purpose of this study was to determine the prevalence of FPC and to define causative FPC-predisposition genes in a Japanese cohort with pancreatic ductal adenocarcinoma (PDAC).We reviewed 1,197 patients with a pathologically proven PDAC and found that 88 (7.3%) were FPC patients who had at least one first-degree relative with PDAC. There were no significant differences between the FPC cases and sporadic cases in terms of gender, age, tumor location, stage, family history of any cancer except PDAC, and personal history of smoking, other cancers, diabetes mellitus and chronic pancreatitis. In the FPC patients, we then investigated the prevalence of germline mutations in 21 genes associated with hereditary predispositions for pancreatic, breast and ovarian cancers by means of the next-generation sequencing using a custom multiple-gene panel. We found that eight (14.5%) of the 54 FPC patients with available germline DNA carried deleterious mutations in BRCA2, PALB2, ATM, or MLH1. These results indicate that a significant fraction of patients with PDAC in Japan have a family history of pancreatic cancer, and some of them harbor deleterious causative mutations in known FPC predisposition genes.
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PMID:Germline mutations in Japanese familial pancreatic cancer patients. 2773 44

Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation in BRCA2 gene. BRCA2 mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carrying BRCA2 mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target BRCA2. The present systematic review collects and analyses the role of BRCA2 alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.
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PMID:The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer. 2807 81