ABSTRACT
BACKGROUND & AIMS: Barrett'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. METHODS: We 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. RESULTS: We 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)). CONCLUSIONS: We 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.
Subject(s)
Barrett Esophagus/genetics , Bone Morphogenetic Proteins/genetics , Genetic Predisposition to Disease , Growth Differentiation Factors/genetics , Polymorphism, Single Nucleotide , T-Box Domain Proteins/genetics , Barrett Esophagus/etiology , Esophageal Neoplasms/genetics , Genome-Wide Association Study , Humans , RiskABSTRACT
At esophagectomy, cancer patients may be malnourished. Nutrition administered central venously is associated with complications, potentially negating nutritional benefits. We aimed to determine the safety of nutrition administered by the peripheral parenteral route (PPN) and record changes in nutritional and surgical outcome. Ivor-Lewis esophagectomy was performed by a single experienced surgeon. Consecutive patients received either 7 days of PPN perioperatively (n = 16) or oral diet reintroduction on the fourth postoperative day (n = 11). Mortality, complications, measures of body composition, protein metabolism, and biochemistry were assessed. Thirty-day mortality was 0% and 18% in the PPN and standard group, respectively. By the 90th day, mortality had increased to 36% in the standard group (P < 0.05). Perioperative PPN can be administered safely in cancer patients undergoing esophagectomy. This form of nutritional support merits further examination by larger, multicenter studies to confirm or refute the observations made in this pilot study.
