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)

Epidemiological evidence has clearly shown a highly significant relationship between Helicobacter pylori infection and the development of duodenal ulcer and distal gastric adenocarcinoma. Despite H. pylori being a common aetiological factor for both disorders, the two disease phenotypes are virtually mutually exclusive. This indicates that the host response to infection has a pivotal role in determining outcome; these disease phenotypes relate to the effect of infection on gastric acid secretion, duodenal ulcer being closely related to sustained acid secretion whereas gastric cancer follows gastric atrophy and impaired gastric acid secretion. Cancer at the oesophageal junction and that associated with Barrett's oesophagus is now the most rapidly increasing tumour in the gastrointestinal tract. The challenge for the next millennium, therefore, is to try and develop methods for identifying patients at risk of developing oesophagogastric cancer. A common feature in the pathogenesis of both gastric and oesophageal adenocarcinoma is inflammation presenting clinically as gastritis and oesophagitis. The pathway from gastritis to gastric atrophy, dysplasia and carcinoma is thought to be a multi-step process, probably triggered by free radicals within the gastric epithelium and increased exposure to luminal carcinogens. However, it has been unclear as to which aspect of the host response determines whether an individual will move along the neoplasia pathway. Recent work has shown that qualitative aspects of the immune environment in the stomach may account for a substantial part of the phenotypic divergence following H. pylori infection. Interleukin-1 beta polymorphisms relate closely to the propensity for an individual to develop distal gastric cancer and maybe useful for predicting risk in family members. In Barrett's oesophagus, we have recently shown that the immune environment may also be important in determining whether an individual will develop cancer. Although we did not find that Barrett's oesophagus was a profoundly inflammatory condition (unlike esophagitis in the squamous epithelium), where there was evidence of inflammation it was qualitatively different from that of oesophagitis in that a Th-2 response with increased expression of IL-4 predominated in Barrett's, whereas a Th-1 proinflammatory response characterised oesophagitis in squamous epithelium. It seems likely that the specific immune environment within Barrett's metaplasia may be an important driver towards dysplasia and carcinoma. Thus, the immune environment in the stomach and esophagus may be critical in determining whether an individual is at risk of developing neoplastic complications of H. pylori infection and gastroesophageal reflux. Identification of the genetic factors which underpin these responses may ultimately result in development of methods to identify individuals at high risk.
 ...
PMID:Acid, helicobacter and immunity: a new paradigm for oesophagogastric cancer. 1159 70

Gastro-oesophageal reflux disease is a multifactorial disease. The roles of environmental, dietary, and host physiological factors are well established. However, the plausible role of Helicobacter pylori infection in gastro-oesophageal reflux disease is still controversial. Furthermore, the role of host genetic factors remains unidentified. Extensive PubMed review of the previous literature has revealed that H. pylori may be negatively associated with gastro-oesophageal reflux disease. Ethnic or inter-individual variations in response to H. pylori infection may also determine disease outcome. Thus, host genetic factors may play an important role in deciding the final outcome of disease. Limited studies have shown that homEM ofCYP2C19, b allele (val105) ofGSTP1, T allele of IL1B-31, 2/2 genotype of IL1RN +2018, 2/2 genotype of IL-10-1082, A/A genotype of CCND1 G870A, and homozygous variant of XPC PAT gene are potential risk factors for the development of gastro-oesophageal reflux disease or its complications such as Barrett's oesophagus and oesophageal adenocarcinoma. There is scant data on the relationship between gastro-oesophageal reflux disease and H. pylori in India, and therefore, further studies are directly required to explore this issue.
 ...
PMID:Pathogenesis of gastro-oesophageal reflux disease: what role do Helicobacter pylori and host genetic factors play? 1856 61