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)

To test the hypothesis that aberrations of DNA repair contribute to susceptibility for the progression of gastroesophageal reflux disease (GERD) into Barrett esophagus (BE) and esophageal adenocarcinoma (EADC), we studied the frequency of polymorphisms of selected DNA repair genes in patients with GERD (n = 126), BE (n = 125) and EADC (n = 56) enrolled in a 2-year prospective case-control study. Controls comprised 95 strictly asymptomatic healthy individuals. Using genomic DNA extracted from blood samples, we identified wild-type and polymorphic variants of XPD (Arg156Arg and Lys751Gln), XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met), and the poly (AT) insertion/deletion of XPC (PAT). Allelic frequencies were compared between cases and controls using logistic regression to calculate age, gender, smoking and alcohol-adjusted odds ratios (OR) and 95% confidence intervals (CI). Patients with EADC demonstrated a significantly higher frequency of the XPC PAT homozygous variant genotype compared with asymptomatic controls (OR = 3.82; 95% CI = 1.05-13.93). Significantly reduced frequencies were seen for the XPD Lys751Gln homozygous variant genotype in patients with EADC (OR = 0.24; 95% CI = 0.07-0.88), and for the XRCC1 Arg399Gln homozygous variant genotype in patients with BE (OR = 0.38; 95% CI = 0.12-0.64) and GERD (OR = 0.29; 95% CI = 0.12-0.66). We conclude that the malignant phenotype probably results from a summation of polymorphic nucleotide excision repair genes showing opposing effects (an increased risk of XPC versus a protective effect of XPD). The protective effect of the homozygous variant of XRCC1 Arg399Gln for GERD and BE suggests that base excision repair alterations may occur early in progression to EADC, likely in response to GERD-induced endogenous oxidative or inflammatory DNA damage. As GERD and BE are highly prevalent in the general population, this protective effect may well explain why only a fraction of individuals with GERD and BE progress into invasive EADC.
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PMID:Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma. 1587 10

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.
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PMID:Pathogenesis of gastro-oesophageal reflux disease: what role do Helicobacter pylori and host genetic factors play? 1856 61