Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastro-oesophageal cancers were ranked as the second cause of death from cancer worldwide despite a steady decrease in incidence for squamous cell carcinoma (SCC) of the oesophagus and distal gastric cancers. Adenocarcinoma of the oesophagus (OAC) is the tumour whose incidence has seen the highest increase in the past 30 years. Most of these cancers are strongly associated with environmental and life style risk factors such as smoking and alcohol for SCC, gastro-oesophageal reflux for OAC and Helicobacter pylori for distal gastric cancer. It may therefore be unsurprising that SCC is associated with polymorphisms in ALDH2 and ADH1B1, enzyme involved in alcohol metabolism, and with CYP1A1, involved in xenobiotics detoxification. OAC, whose incidence in absolute terms remains low, has been much less studied and at best the associations identified with risk are weak. Diffuse type gastric cancers while relatively uncommon have a strong genetic association with mutation of the CDH1 gene and prostate specific cancer antigen (PSCA) was demonstrated in a GWAS to be associated with an increased risk of diffuse gastric cancer but not intestinal type gastric cancer. This family of cancer is more associated with polymorphisms at the IL-1beta, IL-1RN loci and MHTFR loci. Specific strains of H pylori containing the virulence factors VacA s1, VacA m1 and cag A together with polymorphism at the IL-1beta and IL-1RN loci have up to a 87-fold increase in risk for developing intestinal type gastric cancer. While progress has been made to identify genetic variants associated with upper-gastrointestinal cancers, the relative small prevalence for some subtypes underlies the need for consortia, especially in view of the large variations in the prevalence of polymorphisms between different populations.
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PMID:Genetic predisposition to gastro-oesophageal cancer. 2034 91

Relationship between Helicobacter pylori (H. pylori) and gastroesophageal reflux disease (GERD) is controversial. We aimed to review the possible relationship between H. pylori infection and GERD. Epidemiological data indicate an inverse relationship between frequency of H. pylori infection and prevalence of GERD and its complications like Barrett's esophagus and esophageal adenocarcinoma. H. pylori eradication in patients with peptic ulcer disease may be associated with increased risk of development of GERD compared with untreated patients. Infection with cagA bearing strains of H. pylori was associated with less severe GERD including endoscopic esophagitis, possibly due to pangastritis leading to hypochlorhydria. Recent studies on inflammatory markers (IL-1beta and IL-1RN) suggest pro-inflammatory genotypes to be protective against development of severe GERD, especially in patients with H. pylori infection. Identification of candidate genes playing an important role in gastric acid secretion and visceral hypersensitivity to the esophageal epithelium might help in early detection of individuals susceptible to develop GERD. Interplay between H. pylori and host factors play an important role in the pathogenesis of GERD.
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PMID:Gastroesophageal Reflux Disease and Helicobacter pylori: What May Be the Relationship? 2068 Jan 62

Inflammation may play contradictory roles in the pathogenesis of gastroesophageal reflux disease (GERD): gastritis decreases gastric output and reduces the risk of esophagitis, while interleukins may favor mucosal inflammation. The inflammation may cause esogastric motility changes and thus increase the risk of esophagitis. Considering the genetic influence of inflammatory response, we looked for the genetic polymorphisms of IL-1 in GERD manifested as reflux esophagitis. This is a prospective study carried out in GERD and healthy controls. We assessed in these groups the following single nucleotide polymorphisms (SNPs): IL-1A (rs1800587), IL-1B (rs16944), IL-1B (rs1143634) and the VNTR for IL-1RN. Both groups were similar according to biographical data. Reflux esophagitis was confirmed by endoscopy and where necessary by pH-impedance monitoring. Reflux esophagitis was associated only with the polymorphism rs16944. No other correlations with the other three genetic polymorphisms were detected. These data suggest that the diverging effects of proinflammatory factors on the upper digestive tract may have deleterious effect on GERD. The IL-1B (rs16944) SNP correlates with reflux esophagitis.
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PMID:Interleukin-1A and interleukin-1B gene polymorphisms in gastroesophageal reflux disease. 3290 82