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

The expression of cytochrome (CYP) P450 enzymes in human oesophageal mucosa was investigated in a total of 25 histologically non-neoplastic surgical tissue specimens by using specific antibodies in immunoblots and by RT-PCR mRNA analysis. The presence of CYP1A, 2E1, 3A and 4A enzymes was demonstrated by both techniques; CYP2A reactive protein was also detected by immunoblot. The presence of CYP4B1 mRNA was established but no specific antibody was available for detection of the corresponding protein by immunoblot. CYP2B6/7 mRNA was not detected in any sample. The mRNA transcripts for CYP1A1, 2E1, 4A11 and 4B1 were consistently detected in the majority of samples (>84%), whereas CYP1A2 mRNA was only detected in 11 of 19 specimens examined. An RT-PCR method to differentiate CYP3A4 and 3A5 mRNA was developed. This demonstrated CYP3A5 mRNA expression in all samples tested, whereas CYP3A4 mRNA was not detectable, suggesting that CYP3A5 is the major CYP3A protein in human oesophagus. There were significant interindividual variations in the amount of proteins, ranging from 8-fold for CYP4A to 43-fold for CYP2E1. For each patient, data on exposure to risk factors for oesophageal cancer were available, including tobacco smoke, alcohol, gastro-oesophageal reflux and hot beverage consumption. None of these risk factors or other patient characteristics (age, sex, tumour location and tumour stage) were correlated with the protein level of the individual CYP enzymes as determined by quantitation of immunoblot staining. However, the small series of samples precludes any strong conclusion concerning the lack of such correlations. There were no differences between squamous cell carcinomas and adenocarcinomas in either the qualitative or quantitative expression of the CYP enzymes. These data demonstrate that a range of CYP enzymes are expressed in human oesophageal mucosa and indicate that this tissue has the capacity to activate chemical carcinogens to reactive DNA binding metabolites.
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PMID:Characterization of cytochrome P450 expression in human oesophageal mucosa. 1006 60

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