Identification of clinically-informative biomarkers for risk stratification within the spectrum of gastro-esophageal reflux disease in the South African population

Background : Barrett's esophagus is the precursor of esophageal adenocarcinoma with a 5-year survival rate of 25-30%. Objective : To define clinically useful biomarkers for transcriptional profiling in South African patients with Barrett's esophagus in order to identify those patients with an increased cancer risk necessitating intensified surveillance intervals. Materials and method : One-hundred and two patients were recruited for the study. COX-2, c-myb and c-myc mRNA expression were measured using a quantitative PCR method in endoscopically obtained specimens of Barrett's metaplasia (BM, n=26) or dysplasia (BD, n=14) and matching squamous esophageal tissue (n=40), squamous esophageal tissue of patients with erosive esophagitis (n=20), non-erosive esophagitis (n=20) and normal controls (n=20). Two patients with Barrett's adenocarcinoma (BAC) were also studied. Results : Demographic data of the groups were comparable. No significant differences in m-RNA expression levels were observed between ethnic groups for the genes analyzed. In the BD/BAC group 69% (11/16) showed increased c-myb m-RNA expression compared with 35% (9/26) in the BM group (p = 0.03). In the BD patients 19% (3/16) had increased c-myc m-RNA expression compared to none in those with BM and BAC. One patient each with BM and BAC had increased COX-2 m-RNA levels. No significant associations were observed for COX-2 in any of the other study groups. Conclusion : In the South African study cohort c-myb appears to be a clinically useful molecular marker for Barrett's esophagus and increased cancer risk, since m-RNA levels are progressively more over expressed in the metaplasia-dysplasia-adenocarcinoma sequence. Further studies are required to clarify the potential significance c-myc and COX-2 in South African patients with Barrett's esophagus. South African Gastroenterology Review Vol. 3(1) 2005: 5-9