Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the United States, the cumulative mortality or lifetime risk of dying from pancreatic cancer is about 1-2%, but although this form of cancer is rare, nearly all patients die from the disease within one to two years. Because of its lethality, pancreatic cancer now ranks fourth as a cause of death from cancer. There are country-specific differences in rates, perhaps explained by differences in life-style factors or diet. African-Americans in the USA have rates that are about 50% higher than Caucasians. Smoking is the major known risk factor for this cancer, explaining 20-30% of all cases. Another 5-10% of causes are caused by germline mutations, with mutations in BRCA2 being the most frequent. Two background diseases increase the risk of pancreatic cancer-pancreatitis, and diabetes. Major challenges presented by this cancer are: 1) determination of the molecular pathways that make this cancer so aggressive; 2) development of new modalities, perhaps based on proteomics, to enhance early detection.
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PMID:Risk factors for pancreatic cancer. 1584 24

Screening and surveillance for pancreatic cancer and its precursors is a relatively new indication for endoscopic ultrasound. It provides an alternative approach to the ineffective treatment of mostly incurable symptomatic pancreatic cancer. It is currently reserved for individuals with an increased risk for pancreatic ductal adenocarcinoma, such as those who have inherited genetic syndromes (eg, patients who have Peutz-Jeghers syndrome or hereditary pancreatitis, germline mutation carriers of p16 and BRCA2) and at-risk relatives of patients who have familial pancreatic cancer. This article discusses the rationale for performing screening and surveillance, the types of patients who are eligible for screening, the diagnostic modalities and technique for screening, the diagnostic yield of screening, and the ongoing research.
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PMID:Screening and surveillance approaches in familial pancreatic cancer. 1867 2

Some cases of pancreatic cancer (PC) are described to cluster within families. With the exception of PALLD gene mutations, which explain only a very modest fraction of familial cases, the genetic basis of familial PC is still obscure. Here the literature was reviewed in order to list the known genes, environmental factors, and health conditions associated with PC or involved in the carcinogenesis of the pancreas. Most of the genes listed are responsible for various well-defined cancer syndromes, such as CDKN2A (familial atypical mole-multiple melanoma, FAMMM), the mismatch repair genes (Lynch Syndrome), TP53 (Li-Fraumeni syndrome), APC (familial adenomatous polyposis), and BRCA2 (breast-ovarian familial cancer), where PC is part of the cancer spectrum of the disease. In addition, in this review I ranked known/possible risk factors extending the analysis to the hereditary pancreatitis (HP), diabetes, or to specific environmental exposures such as smoking. It appears that these factors contribute strongly to only a small proportion of PC cases. Recent work has revealed new genes somatically mutated in PC, including alterations within the pathways of Wnt/Notch and DNA mismatch repair. These new insights will help to reveal new candidate genes for the susceptibility to this disease and to better ascertain the actual contribution of the familial forms.
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PMID:Genetic predisposition and environmental risk factors to pancreatic cancer: A review of the literature. 1915 Apr 14

There has been substantial recent progress in our ability to image and sample the pancreas leading to the improved recognition of benign and premalignant conditions of the pancreas such as autoimmune pancreatitis (AIP) and mucinous lesions (mucinous cystic neoplasms [MCN] and intraductal papillary mucinous neoplasms [IPMN]), respectively. Clinically relevant and difficult situations that continue to be faced in this context include differentiating MCN and IPMN from nonmucinous pancreatic cysts, the early detection of malignant degeneration in MCN and IPMN, and accurate differentiation between pancreatic cancer and inflammatory masses, especially AIP. These challenges arise primarily due to the less than perfect sensitivity for malignancy utilizing cytological samples obtained via EUS and ERCP. Aspirates from pancreatic cysts are often paucicellular further limiting the accuracy of cytology. One approach to improve the diagnostic yield from these very small samples is through the use of molecular techniques. Because the development of pancreatic cancer and malignant degeneration in MCN and IPMN is associated with well studied genetic insults including oncogene activation (eg, k-ras), tumor suppressor gene losses (eg, p53, p16, and DPC4), and genome maintenance gene mutations (eg, BRCA2 and telomerase), detecting these molecular abnormalities may aid in improving our diagnostic accuracy. A number of studies have shown the utility of testing clinical samples from pancreatic lesions and bile duct strictures for these molecular markers of malignancy to differentiate between cancer and inflammation. The information from these studies will be discussed with emphasis on how to use this information in clinical practice.
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PMID:Differentiating neoplastic from benign lesions of the pancreas: translational techniques. 1989

Recently, PALB2 was reported to be a new pancreatic cancer susceptibility gene as determined by exomic sequencing, as truncating PALB2 mutations were identified in 3 of 96 American patients with familial pancreatic cancer (FPC). Representing the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) and the German National Case Collection for Familial Pancreatic Cancer (FaPaCa), we evaluated whether truncating mutations could also be detected in European FPC families. We have directly sequenced the 13 exons of the PALB2 gene in affected index patients of 81 FPC families. An index patient was defined as the first medically identified patient, stimulating investigation of other members of the family to discover a possible genetic factor. None of these patients carried a BRCA2 mutation. We identified three (3.7%) truncating PALB2 mutations, each producing different stop codons: R414X, 508-9delAG and 3116delA. Interestingly, each of these three families also had a history of breast cancer. Therefore, PALB2 mutations might be causative for FPC in a small subset of European families, especially in those with an additional occurrence of breast cancer.
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PMID:PALB2 mutations in European familial pancreatic cancer families. 2041 13

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

Familial pancreatic cancer (FPC) describes families with at least two first-degree relatives with confirmed exocrine pancreatic cancer that do not fulfil the criteria of other inherited tumour syndromes with increased risks of pancreatic cancer, such as Peutz-Jeghers syndrome, hereditary pancreatitis, and hereditary breast and ovarian cancer. The inheritance of FPC is mostly autosomal dominant and with a heterogeneous phenotype. The major gene defect is yet to be identified, although germline mutations in BRCA2, PALB2 and ATM are causative in some FPC families. Expert consensus conferences considered it appropriate to screen for pancreatic cancer in high-risk individuals using a multidisciplinary approach under research protocol conditions. However, neither biomarkers nor reliable imaging modalities for the detection of high-grade precursor lesions are yet available. Most screening programmes are currently based on findings from endoscopic ultrasonography and MRI, and data has demonstrated that precursor lesions of pancreatic cancer can be identified. No consensus exists regarding the age to initiate or stop screening and the optimal intervals for follow-up. Timing and extent of surgery as a treatment for FPC are debated. This Review focuses on the clinical phenotype of FPC, its histopathological characteristics, known underlying genetic changes and associated genetic counselling and screening.
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PMID:Familial pancreatic cancer--current knowledge. 2266 88

It is estimated that 5% to 10% of pancreatic cancer is familial. Although there is evidence of a major pancreatic cancer susceptibility gene, the majority of families with multiple cases of pancreatic cancer do not have an identifiable causative gene or syndrome. However, a subset of pancreatic cancer is attributable to known inherited cancer predisposition syndromes, including several hereditary breast cancer genes (BRCA1, BRCA2, and PALB2), CDKN2A, hereditary pancreatitis, hereditary nonpolyposis colorectal cancer, and Peutz-Jeghers syndrome. In addition to explaining a proportion of familial pancreatic cancer, individuals with these conditions are at increased risk for pancreatic cancer. Relatives from familial pancreatic cancer kindreds without one of these identifiable syndromes may have as high as a 32-fold risk of pancreatic cancer, depending on the number of affected first-degree relatives. Such high-risk individuals may benefit from increased surveillance, and strategies for early detection of pancreatic cancer are under evaluation.
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PMID:Genetic testing by cancer site: pancreas. 2284 37

The term 'familial pancreatic cancer (FPC) defines families with at least two first-degree relatives with confirmed pancreatic cancer that do not fulfill the criteria of other inherited cancer syndromes with an increased risk for the development of PC, such as Peutz-Jeghers syndrome, hereditary pancreatitis and hereditary breast and ovarian cancer. FPC is a mostly autosomal dominant inherited tumor syndrome with a heterogeneous phenotype. The major genetic defect has not been identified yet, although mutations, for example in the BRCA2 gene, could be identified in some FPC families. Nevertheless, most experts recommend participation in screening and surveillance programs to high-risk individuals. Most board-approved screening programs are based on endoscopic ultrasound. The first data on the prospective screening of high-risk individuals have demonstrated that precursor lesions of PC can be identified, but false-positive findings do occur.
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PMID:Familial pancreatic cancer: current status. 2348 6

Beset by poor prognosis, pancreatic ductal adenocarcinoma is classified as familial or sporadic. This review elaborates on the known genetic syndromes that underlie familial pancreatic cancer, where there are opportunities for genetic counseling and testing as well as clinical monitoring of at-risk patients. Such subsets of familial pancreatic cancer involve germline cationic trypsinogen or PRSS1 mutations (hereditary pancreatitis), BRCA2 mutations (usually in association with hereditary breast-ovarian cancer syndrome), CDKN2 mutations (familial atypical mole and multiple melanoma), or DNA repair gene mutations (e.g., ATM and PALB2, apart from those in BRCA2). However, the vast majority of familial pancreatic cancer cases have yet to have their genetic underpinnings elucidated, waiting in part for the results of deep sequencing efforts.
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PMID:Familial pancreatic cancer: genetic advances. 2439 43


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