Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Humans are exposed to preformed N-nitroso compounds (NOC), but also to a wide range of precursors and nitrosating agents which can react in vivo to form potentially carcinogenic NOC and diazo compounds. Nitrite, nitrate and nitrosating agents can also be synthesized endogenously in enzymic reactions mediated by bacteria, activated macrophages and neutrophils. The latter two cell types generate, via the enzyme nitric oxide synthase, the nitric oxide radical that is involved in cytotoxicity, and is believed to be involved in formation of carcinogenic nitrosamines, DNA base deamination and oxidative damage. Thus endogenous NOC formation, DNA damage and gene mutations in humans could occur at various sites of the body such as the stomach and chronically infected or inflamed organs. Sensitive procedures to estimate the exposure of humans to NOC have been developed and applied in ecological and cross-sectional studies. These have shown that inhabitants of high-risk areas for stomach and esophageal cancer, patients with urinary tract infections (at risk for bladder cancer) and Thai subjects infected with liver fluke (at risk for cholangiocarcinoma) had significantly higher exposure to endogenous NOC. Clinical studies have examined the model of stomach carcinogenesis based on intragastric nitrosation, but the precise roles of bacterial overgrowth and of Helicobacter pylori infection in NOC synthesis and/or inducing oxidative stress in stomach mucosa remain to be clarified. Together these results support the role of NOC and other nitrite-derived mutagens in human cancer etiology, in particular when exposure starts early in life and persists over a long period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenously formed N-nitroso compounds and nitrosating agents in human cancer etiology. 133 85

The incidence of carcinoma of the esophagogastric junction was evaluated based on data from the Japanese Esophageal Cancer Registry during the periods 1976-1994 and the Japanese Gastric Cancer Registry during 1963-1989. Although the number of cases of carcinoma of the esophagogastric junction had increased, the incidence was evaluated to have decreased. On the other hand, there are some reports that the incidence of carcinoma of the esophagogastric junction and the cardia have increased in the USA and western European countries. The trend is controversial and it is necessary to evaluate the location of lesions accurately. Possible explanations for the increasing trend etc. therefore are smoking and alcohol intake, Helicobacter pylori infection, hiatal hernia. To determine the incidence of carcinoma of the esophagogastric junction more reliably, the nationwide cancer registry program should continue.
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PMID:[Does incidence of carcinoma of the esophagogastric junction increase?]. 984 37

Cancers of the esophagus, gastroesophageal junction (including the gastric cardia), and stomach represent three separate diseases with marked epidemiologic variations. The Department of Veterans Affairs computerized database records the ethnicity of all hospitalized patients throughout the United States, which provides an opportunity to study the influence of ethnicity on cancer rates in a uniform health-care system. All hospitalized patients, from 1980 through 1995, with a diagnosis of upper gastrointestinal cancer were identified. For each ethnic group and cancer type, hospitalization was expressed as an age-adjusted proportional rate per 10,000 hospitalizations from all causes. Hospitalization with gastric cancer was most frequent among Asians (48.4 per 10,000 hospitalizations) followed by blacks (33.3), Hispanics (28.7), American Indians (20.3), and whites (12.0). Adenocarcinoma of the gastroesophageal junction accounted for 5.9 per 10,000 hospitalizations among Asians, 4.5 among whites, and 4.5 among Hispanics. Gastroesophageal junction cancer was lowest among blacks (2.9) and American Indians (2.4). Finally, squamous cell carcinoma of the esophagus was frequent among blacks, 68.2 per 10,000, followed by Hispanics (36.4) and Asians (27.8), and was low among whites 24.0 and American Indians (21.5). Esophageal cancer rates remained stable in all ethnic groups from 1980 through 1995; gastroesophageal junction cancer rates increased particularly among whites, whereas gastric cancer rates declined in whites and blacks but not in Hispanics. There were significant ethnic differences in the occurrence of gastroesophageal malignancies among US military veterans. Environmental factors may explain some of these differences. Differential rates of Helicobacter pylori infection with resultant gastric atrophy and reduced acid output led to a greater risk for gastric cancer, but a reduced risk for reflux disease and cardiac cancer.
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PMID:Ethnic variations in the occurrence of gastroesophageal cancers. 1007 14

The incidence of adenocarcinoma of the esophagus and esophagogastric junction (EGJ) has been increasing over the past 15 years in western countries. Surgical series and population-based studies show that, by 1994, adenocarcinomas of the esophagus accounted for half of all esophageal cancer among white men. The causes of this increase in incidence remain to be elucidated. Esophageal adenocarcinomas and a portion of EGJ adenocarcinomas arise from long and short segments of specialized intestinal metaplasia (Barrett's esophagus). The prevalence of long segments of Barrett's esophagus (> 3 cm) in patients having endoscopy for reflux symptoms is 3%, and 1% in those undergoing endoscopy for any clinical indication. However, a silent majority of patients with Barrett's esophagus remain unrecognized in the general population and may not be diagnosed unless adenocarcinoma develops. Recent studies document a rise in the diagnosis of specialized intestinal metaplasia of the cardia. Nearly all these patients have associated carditis, and Helicobacter pylori infection has been linked to this condition. The possible origin of EGJ adenocarcinomas in the sequence carditis--specialized intestinal metaplasia needs to be clarified. Smoking and obesity are additional risk factors for adenocarcinoma of the esophagus and EGJ. Current data does not confirm H. pylori as a risk factor for cancer of the EGJ.
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PMID:Epidemiology of esophageal cancer, especially adenocarcinoma of the esophagus and esophagogastric junction. 1069 34

Diet plays a role in the prevention and development of gastrointestinal cancers. The majority of available research consists of case-control studies, but the number of clinical trials is growing. The dietary recommendations to reduce gastrointestinal cancer risk include lowering total energy, fat, and saturated fat intake; avoidance of grilled and smoked foods; avoidance of alcohol; and increasing intake of fruits, vegetables, and fiber. Studies of esophageal cancer support these dietary approaches, with the exception of dietary fat reduction and increased green tea intake. For gastric cancer, consuming additional fruits and vegetables, including those high in ascorbic acid, may reduce risk, and the capacity for diet to alter Helicobacter pylori infection should be explored. Recent interventional trials do not support a role for high-fiber or low-fat diets in reducing development of colon adenomas, although the evidence does not rule out efficacy at earlier stages of disease. Finally, the evidence for a relationship between pancreatic cancer and diet remains sparse and warrants additional investigation.
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PMID:Nutrition and diet in the development of gastrointestinal cancer. 1266 16

Genetic polymorphisms may modify the effects of environmental risk factors on cancer occurrence. We have recently launched a comprehensive epidemiologic project, HERPACC II (Hospital-based Epidemiologic Research Program at Aichi Cancer Center II), including both lifestyle and polymorphism data, following HERPACC-I which solely concentrated on lifestyle data. As of April 2001, about 3000 samples of DNA are being stored to conduct case-control studies. Genotyping of 46 polymorphisms has been conducted at the laboratory of the Division of Epidemiology and Prevention. Twelve case-control studies and two papers on a new PCR method, PCR-CTPP (polymerase chain reaction with confronting two-pair primers), have been accepted for publication. Significant findings in Japanese were found for 1) gene-environment interaction for esophageal cancer between heavy drinking and aldehyde dehydrogenase 2 (ALDH2), 2) malignant lymphoma risk with methylenetetrahydrofalate reductase (MTHFR) and methionine synthase (MS), 3) interactions between smoking and two polymorphisms, interleukin 1B (IL-1B) and myeloperoxidase (MPO) for Helicobacter pylori infection, and 4) smoking habits with dopamine receptor D2 (DRD2) and IL-1B. Further studies on interactions with polymorphisms will continue to be conducted for Japanese, using larger sizes of samples.
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PMID:Gene-environment Interactions and Polymorphism Studies of Cancer Risk in the Hospital-based Epidemiologic Research Program at Aichi Cancer Center II (HERPACC-II). 1271 40

Most available information on the epidemiology of Barrettacute;s esophagus (BE) relates to patients with long segments (> 3 cm) of specialized intestinal metaplasia (SIM). Its prevalence is 3% in patients undergoing endoscopy for reflux symptoms and 1% in those undergoing endoscopy for any clinical indication. The latter prevalence is similar to the 1% found in autopsy series. A "silent majority" with BE remain unrecognized in the general population. BE is more common in men, and the prevalence rises with age. Recent endoscopic series document a rise in the diagnosis of endoscopically apparent short segments (< 3 cm) of BE (SSBE). The prevalence of SSBE in both unselected and reflux patients is 8% to 12%. Specialized intestinal metaplasia at the cardia, below a normal-appearing squamocolumnar junction, has been reported to vary from 6% to 25% in patients presenting for upper endoscopy. Unlike patients with long segment Barrett's esophagus (LSBE), the role of gastroesophageal reflux disease in the pathogenesis of SSBE and SIM of the cardia is controversial. Recent data suggest that the etiology of SIM of the cardia might be secondary to Helicobacter pylori infection, although the role of other environmental factors cannot be ruled out. The incidence of adenocarcinoma of the esophagus and esophagogastric juction (EGJ) has been increasing over the past 15 years in Western countries. Surgical series and population-based studies show that by 1994 adenocarcinomas of the esophagus accounted for half of all esophageal cancer among white men. LSBE and SSBE predispose to the development of adenocarcinoma of the esophagus and EGJ. The role of SIM of the cardia as a precursor lesion for EGJ adenocarcinoma is still unclear. The prevalences of dysplasia in LSBE and SSBE are around 6% and 8%, respectively. The incidence of adenocarcinoma in patients with LSBE is about 1 in 100 patient-years. Cancer risk for SSBE and SIM at the cardia is unknown. Smoking and obesity increase the risk for esophageal and EGJ adenocarcinomas.
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PMID:Trends in incidence and prevalence of specialized intestinal metaplasia, barrett's esophagus, and adenocarcinoma of the gastroesophageal junction. 1291 64

The incidence of esophageal adenocarcinoma has risen rapidly over the past 3 decades. This increase had been most dramatic among white men. It has supplanted squamous cell carcinoma as the predominant histologic type of esophageal cancer in the United States. The reasons underlying this phenomenon are not readily apparent. Improvements in diagnostic techniques and changes in cancer classification may explain some of the rise in reported incidence rates, but detection bias and misclassification bias do not appear adequate to explain the increase entirely. Risk factors for esophageal adenocarcinoma are reviewed, with particular emphasis on their role in underlying the rising cancer incidence. The etiologic factors most likely to explain the current epidemic of esophageal adenocarcinoma are the parallel epidemic of obesity, rising use of lower esophageal sphincter-relaxing medications, decreasing Helicobacter pylori infection, changes in the Western diet, and distant smoking habits.
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PMID:The changing epidemiology of esophageal adenocarcinoma. 1465 11

Although significant advancements have been made in the treatment of esophageal cancer, this aggressive malignancy commonly presents as locally advanced disease with a poor prognosis. Despite improvements in the detection of premalignant pathology, newer preventative strategies, and the development of more effective combination therapies, the overall incidence of esophageal carcinomas has risen. A clear association has been established between the development of esophageal cancer and Helicobacter pylori infection, gastroesophageal reflux disease, smoking, and heavy alcohol use. However, the growing number of newly diagnosed esophageal adenocarcinomas, despite widespread treatments with proton pump inhibitors and the eradication of H. pylori, leaves the medical community searching for more answers. There is a potential link between esophageal adenocarcinoma and obesity. Common presenting symptoms of esophageal cancer are dysphagia, odynophagia, and progressive weight loss. The initial assessment for patients with these symptoms is made with double-contrast barium esophagraphy. Treatment modalities include surgery, chemotherapy, radiation therapy, or a combination of modalities. Prevention strategies include smoking and alcohol cessation.
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PMID:Esophageal cancer: a review and update. 1683 35

Hedgehog, BMP/TGFbeta, FGF, WNT and Notch signaling pathways constitute the stem cell signaling network, which plays a key role in a variety of processes, such as embryogenesis, maintenance of adult tissue homeostasis, tissue repair during chronic persistent inflammation, and carcinogenesis. Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH) bind to PTCH1/PTCH or PTCH2 receptor to release Smoothened (SMO) signal transducer from Patched-dependent suppression. SMO then activates STK36 serine/threonine kinase to stabilize GLI family members and to phosphorylate SUFU for nuclear accumulation of GLI. Hedgehog signaling activation leads to GLI-dependent transcriptional activation of target genes, such as GLI1, PTCH1, CCND2, FOXL1, JAG2 and SFRP1. GLI1-dependent positive feedback loop combined with PTCH1-dependent negative feedback loop gives rise to transient proliferation of Hedgehog target cells. Iguana homologs (DZIP1 and DZIP1L) and Costal-2 homologs (KIF7 and KIF27) are identified by comparative integromics. SHH-dependent parietal cell proliferation is implicated in gastric mucosal repair during chronic Helicobacter pylori infection. BMP-RUNX3 signaling induces IHH expression in surface differentiated epithelial cells of stomach and intestine. Hedgehog signals from epithelial cells then induces FOXL1-mediated BMP4 upregulation in mesenchymal cells. Hedgehog signaling is frequently activated in esophageal cancer, gastric cancer and pancreatic cancer due to transcriptional upregulation of Hedgehog ligands and epigenetic silencing of HHIP1/HHIP gene, encoding the Hedgehog inhibitor. However, Hedgehog signaling is rarely activated in colorectal cancer due to negative regulation by the canonical WNT signaling pathway. Hedgehog signaling molecules or targets, such as SHH, IHH, HHIP1, PTCH1 and GLI1, are applied as biomarkers for cancer diagnostics, prognostics and therapeutics. Small-molecule inhibitors for SMO or STK36 are suitable to be used for treatment of Hedgehog-dependent cancer.
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PMID:Hedgehog signaling pathway and gastrointestinal stem cell signaling network (review). 1708 4


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