Background & AimsBarrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.MethodsWe performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.ResultsWe identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9).ConclusionsWe identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.
Objective: To investigate the relation between the measured intravascular blood volume (BV) and current methods of indirectly assessing BV status in sick preterm infants on the first day of life. Methods: Thirty eight preterm infants of gestation 24-32 weeks (median 30) and weight 480-2060 g (median 1220) were studied. Red cell volume was measured by the fetal haemoglobin dilution method in six infants and by the biotin labelled autologous red cell dilution method in the remaining 32. Total BV was calculated by dividing red cell volume by packed cell volume. Indirect assessments of BV status using heart rate (HR), core-peripheral temperature difference, mean arterial pressure, base excess, and packed cell volume were recorded. Results: The mean (SD) initial measured BV was 71 (12) ml/kg (range 53-105). The mean HR was 148 beats/min (range 130-180), which correlated positively (r = 0.39, p = 0.02) with BV (higher HR was associated with higher BV). The mean base excess was 23.19 mmol/l (range 218 to +6.2). The negative base excess correlated significantly positively (r = 0.41, p , 0.01) with BV (more acidotic babies tended to have higher BV). There was no significant correlation between core-peripheral temperature difference, mean arterial pressure, or packed cell volume and BV. Regression analysis showed that base excess and HR were significantly related to BV; base excess alone can predict variability in BV only to17%, and base excess with HR can predict variability in BV to 29%. Conclusion: The conventional clinical and laboratory indices are poor predictors of measured blood volume.
More than half of the patients with symptoms of colorectal cancer are found to have extracolonic pathologies by CTC analysis. However, the proportion of patients found to have extracolonic malignancies after 1 year of CTC examination is not significantly greater than after barium enema or colonoscopy examinations. International Standard Randomised Controlled Trials no: 95152621.isrctn.com.
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