Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10-8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10-5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10-10; OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10-16; OR = 1.75; 95% CI, 1.64-1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes.
- Publikační typ
- časopisecké články MeSH
xiii, 181 pages : illustrations
Introduction -- Pathology and classification of cystic tumors of the pancreas -- Cytology in cystic tumors of the pancreas -- Molecular biology of cystic tumors of the pancreas -- Epidemiology of cystic tumors of the pancreas -- CT in cystic tumors of the pancreas -- MR in cystic tumors of the pancreas -- EUS in cystic tumors of the pancreas -- Endoscopy in cystic tumors of the pancreas -- PET-scan in cystic tumors of the pancreas -- When and how to follow patients with cystic tumors of the pancreas?- The standard surgical treatment of cystic tumors of the pancreas -- Parenchyma sparing pancreatic resections in cystic tumors of the pancreas -- Minimally invasive pancreatic surgery for cystic tumors of the pancreas -- Ablation modalities in cystic tumors of the pancreas -- How to manage cystic tumors of the pancreas in high risk individuals -- How to follow patients with resected cystic tumors of the pancreas?- The role of chemo/radiotherapy in cystic tumors of the pancreas -- A Comparative analysis between the IAP and UEG guidelines for cystic tumors of the pancreas
This book provides a detailed, up-to-date overview of cystic tumors of the pancreas, with coverage of all aspects of diagnosis and treatment (medical, endoscopic, and surgical). After opening chapters on pathology and classification, cytology, molecular biology, and epidemiology, the role of each of the relevant diagnostic methods is carefully examined. The treatment-related chapters describe surgical approaches, including minimally invasive surgery, as well as ablation modalities and chemo-radiotherapy. Thorough guidance is also provided specifically on the management of cystic tumors in high-risk cases and on follow-up. The authors are global opinion leaders in their field who have contributed cutting-edge chapters, with emphasis on clear diagnostic and therapeutic algorithms and with numerous supporting tables and illustrations. Owing to the widespread use of imaging modalities, clinicians are being confronted by an increasing number of patients with cystic tumors of the pancreas, ranging from benign cysts to metastasized malignancies. The widening spectrum of available diagnostic measures has resulted in controversy over the choice of further means of investigation when cystic changes are encountered, and the growth in therapeutic options has similarly been accompanied by considerable debate over their use. Against this background, Cystic Tumors of the Pancreas will be a valuable source of relevant information for both clinicians and surgeons and will also be of interest to radiologists, pathologists, and basic scientists
