Citations 2
eQTL Set–Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma
Wang, Xiaoyu , Gharahkhani, Puya , Levine, David , Fitzgerald, Rebecca C. , Corley, Douglas A. , Risch, Harvey A. , Bernstein, Leslie , Chow, Wong‐Ho , Onstad, Lynn , Shaheen, Nicholas J. , Lagergren, Jesper , Hardie, Laura J. , Wu, Anna H. , Liu, Geoffrey , Anderson, Lesley , Iyer, Prasad G. , Gammon, Marilie D. , Caldas, Carlos , Ye, Weimin , Barr, Hugh , Harrison, Rebecca , Watson, R.G. Peter , Attwood, Stephen , Chegwidden, Laura , Love, Sharon , MacDonald, David , Prenen, Hans , Ott, Katja , Lang, Hauke , Mayershofer, Rupert , Knapp, Michael , Veits, Lothar , Gerges, Christian , Weismüller, Josef , Reeh, Matthias , Nöthen, Markus M. , Izbicki, Jakob R. , Manner, Hendrik , Neuhaus, Horst , Böhmer, Anne C. , Hölscher, Arnulf H. , Anders, Mario , Pech, Oliver , Schumacher, Brigitte , Schmidt, Claudia , Noder, Tania , Lorenz, Dietmar , Vieth, Michael , May, Andrea , Kreuser, Nicole , Becker, Jessica , Ell, Christian , Tomlinson, Ian , Palles, Claire , Whiteman, David C. , MacGregor, Stuart , Schumacher, Johannes , Vaughan, Thomas L. , Buas, Matthew F. , Dai, James Y. , Levine, David M , Gockel, Ines , Corley, Douglas A , Risch, Harvey A , Bernstein, Leslie , Chow, Wong-Ho , Onstad, Lynn , Shaheen, Nicholas J , Lagergren, Jesper , Hardie, Laura J , Wu, Anna H. , Pharoah, Paul D P , Liu, Geoffrey , Anderson, Lesley A , Iyer, P G , Caldas, Carlos , Ye, Weimin , Barr, Hugh , Moayyedi, Paul , Harrison, Rebecca , Watson, R G Peter , Attwood, Stephen , Chegwidden, Laura , Love, Sharon B , MacDonald, David , deCaestecker, John , Prenen, Hans , Ott, Katja , Moebus, Susanne , Venerito, Marino , Lang, Hauke , Mayershofer, Rupert , Knapp, Michael , Veits, Lothar , Gerges, Christian , Weismüller, Josef , Reeh, Matthias , Nöthen, Markus M , Izbicki, Jakob R , Manner, Hendrik , Neuhaus, Horst , Rösch, Thomas , Böhmer, Anne C , Hölscher, Arnulf H , Anders, Mario , Pech, Oliver , Schumacher, Brigitte , Schmidt, Claudia , Schmidt, Thomas , Noder, Tania , Lorenz, Dietmar , Vieth, Michael , May, Andrea , Hess, Timo , Kreuser, Nicole , Becker, Jessica , Ell, Christian , Tomlinson, Ian , Palles, Claire , Jankowski, Janusz A , Whiteman, David C , MacGregor, Stuart , Schumacher, Johannes , Vaughan, Thomas L , Buas, Matthew F , Dai, James Y , Gharahkhani, Puya , Pharoah, Paul D.P. , Moayyedi, Paul , Caestecker, John de , Moebus, Susanne , Hess, Timo , Jankowski, Janusz
Cancer Epidemiology, Biomarkers & Prevention | June 16, 2022 | Volume: 31 | Issue: 9 | Pages: 1735-1745
Abstract Background: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. Results: Although the standard approach did not identify significant signals, the eQTL set–based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). Conclusions: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set–based genetic association approach. Impact: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set–based genetic association approach as an alternative method for TWAS analysis.
How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery)
Pauwels, Ans, Andrews, Christopher N. , Attwood, Stephen , Berrisford, Richard, Bisschops, Raf , Boeckxstaens, Guy E. , Bor, Serhat , Bredenoord, Albert J. , Cicala, Michele , Corsetti, Maura , Fornari, Fernando , Gyawali, C. Prakash , Hatlebakk, Jan, Johnson, Scott, Lerut, Toni, Lundell, Lars, Mattioli, Sandro , Omari, Taher , Pandolfino, John E. , Penagini, Roberto , Rice, Thomas W., Roelandt, Philip , Rommel, Nathalie , Savarino, Vincenzo , Vanuytsel, Tim , Vela, Marcelo F. , Watson, David I. , Tack, Jan , Lerut, Antoon , Tack, Jan , Gyawali, C P , Corsetti, M , Penagini, Roberto , Bisschops, Raf , Bor, Serhat , Omari, Taher , Boeckxstaens, Guy , Andrews, Christopher N , Boecxstaens, Veerle , Miwa, Hiroto , Nafteux, Philippe Robert , Sifrim, Daniel , Suzuki, Hidekazu , Tutuian, Radu I. , Zerbib, Frank
Gut | August 2, 2019 | Volume: 68 | Issue: 11 | Pages: 1928-1941
Objective Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery. Design We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous. Results Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett’s oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis. Conclusion With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.