GWAS meta-analysis of 16 790 patients with Barrett’s oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level

Schröder, Julia; Chegwidden, Laura; Maj, Carlo; Gehlen, Jan; Speller, Jan; Böhmer, Anne C.; Borisov, Oleg; Hess, Timo; Kreuser, Nicole; Venerito, Marino; Alakus, Hakan; May, Andrea; Gerges, Christian; Schmidt, Thomas; Thieme, René; Heider, Dominik; Hillmer, Axel M.; Reingruber, Julian; Lyros, Orestis; Dietrich, Arne; Hoffmeister, Albrecht; Lordick, Florian; Stocker, Gertraud; Hohaus, Michael; Reim, Daniel; Kandler, Jennis; Müller, Michaela; Ebigbo, Alanna; Fuchs, Claudia; Bruns, Christiane; Hölscher, Arnulf H.; Lang, Hauke; Grimminger, Peter; Dakkak, Dani; Vashist, Yogesh K.; May, Sandra; Görg, Siegfried; Franke, André; Ellinghaus, David; Galavotti, Sara; Veits, Lothar; Weismüller, Josef; Dommermuth, Jens; Benner, Udo; Rösch, Thomas; Messmann, Helmut; Schumacher, Brigitte; Neuhaus, Horst; Schmidt, Carsten Oliver; Wissinowski, Thaddäus T; Nöthen, Markus M.; Dong, Jing; Ong, Jue‐Sheng; Buas, Matthew F.; Thrift, Aaron P.; Vaughan, Thomas L.; Tomlinson, Ian; Whiteman, David C.; Fitzgerald, Rebecca; Jankowski, Janusz; Mayr, Andreas; Gharahkhani, Puya; MacGregor, Stuart; Gockel, Ines; Palles, Claire; Schumacher, Johannes

doi:10.1136/gutjnl-2021-326698

“…To examine the association of each genetic instrument with cancer risk, we used summary GWAS effect estimates from: (1) Online consortia resources, for breast (BCAC; https://bcac.ccge.medschl.cam.ac.uk/, accessed July 2022) and prostate cancer (PRACTICAL; http://practical.icr.ac.uk/; accessed July 2022) 7,8 ; (2) GWAS catalogue (https://www.ebi.ac.uk/gwas/), for ovarian, endometrial and lung cancers (accessed September 2022) 9–11 ; (3) Investigators of published work, for colorectal cancer (CRC), renal cell carcinoma (RCC) and oesophageal cancer 12–14 . Cancer subtype summary statistics were available for lung, breast and ovarian cancers.…”

Section: Methodsmentioning

confidence: 99%

“…( and oesophageal cancer [12][13][14] . Cancer subtype summary statistics were available for lung, breast and ovarian cancers.…”

Section: Cancer Gwas Summary Statisticsmentioning

confidence: 99%

Risk factors for eight common cancers revealed from a phenome-wide Mendelian randomisation analysis of 378,142 cases and 485,715 controls

Went

¹

,

Sud

²

,

Mills

³

et al. 2023

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For many cancers there are few well-established risk factors. Summary data from genome-wide association studies (GWAS) can be used in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to identify causal relationships. We performed a MR-PheWAS of breast, prostate, colorectal, lung, endometrial, oesophageal, renal, and ovarian cancers, comprising 378,142 cases and 485,715 controls. To derive a more comprehensive insight into disease aetiology we systematically mined the literature space for supporting evidence. We evaluated causal relationships for over 3,000 potential risk factors. In addition to identifying well-established risk factors (smoking, alcohol, obesity, lack of physical activity), we provide evidence for specific factors, including dietary intake, sex steroid hormones, plasma lipids and telomere length as determinants of cancer risk. We also implicate molecular factors including plasma levels of IL-18, LAG-3, IGF-1, CT-1, and PRDX1 as risk factors. Our analyses highlight the importance of risk factors that are common to many cancer types but also reveal aetiological differences. A number of the molecular factors we identify have the potential to be biomarkers. Our findings should aid public health prevention strategies to reduce cancer burden. We provide a R/Shiny app (https://mrcancer.shinyapps.io/mrcan/) to visualise findings.

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“…( and oesophageal cancer [12][13][14] . Cancer subtype summary statistics were available for lung, breast and ovarian cancers.…”

Section: Cancer Gwas Summary Statisticsmentioning

confidence: 99%

Risk factors for eight common cancers revealed from a phenome-wide Mendelian randomisation analysis of 378,142 cases and 485,715 controls

Went

¹

,

Sud

²

,

Mills

³

et al. 2023

Preprint

Self Cite

0

View full text Add to dashboard Cite

For many cancers there are few well-established risk factors. Summary data from genome-wide association studies (GWAS) can be used in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to identify causal relationships. We performed a MR-PheWAS of breast, prostate, colorectal, lung, endometrial, oesophageal, renal, and ovarian cancers, comprising 378,142 cases and 485,715 controls. To derive a more comprehensive insight into disease aetiology we systematically mined the literature space for supporting evidence. We evaluated causal relationships for over 3,000 potential risk factors. In addition to identifying well-established risk factors (smoking, alcohol, obesity, lack of physical activity), we provide evidence for specific factors, including dietary intake, sex steroid hormones, plasma lipids and telomere length as determinants of cancer risk. We also implicate molecular factors including plasma levels of IL-18, LAG-3, IGF-1, CT-1, and PRDX1 as risk factors. Our analyses highlight the importance of risk factors that are common to many cancer types but also reveal aetiological differences. A number of the molecular factors we identify have the potential to be biomarkers. Our findings should aid public health prevention strategies to reduce cancer burden. We provide a R/Shiny app (https://mrcancer.shinyapps.io/mrcan/) to visualise findings.

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“…In addition, Among the 2,628 institutions, Mayo Clinic (United States), Karolinska Institute (Sweden), University of Washington (United States), Fred Hutchinson Cancer Research Center (United States), University of Padua (Italy), and University of Uppsala (Sweden) contributed signi cantly to this eld and remained cooperative with other institutions. Lagergren J published the most articles over the past two decades, primarily on Barrett's esophagus and esophageal adenocarcinoma [27][28][29].…”

Section: Analysis Of the Top 10 Citationsmentioning

confidence: 99%

A Bibliometric and Visual Analysis of Obesity and Gastroesophageal Reflux Disease

Tan,

Luo,

Wang

2023

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Aim To assess the research status, hotspots, and frontiers related to obesity and gastroesophageal reflux disease (GERD) using bibliometric approaches. Material and Methods Bibliometric analysis of the field of obesity and GERD was conducted based on database of the Web of Science Core Collection (WOSCC) from its inception to October 20, 2022. Several factors are analyzed and mapped using VOSviewer software, including the total number of publications, the number of resources and journals, countries, authors, and intellectual networks, as well as the co-citation analysis of keywords and references. Results A total of 2,306 papers from 480 journals with 10,010 authors from 2,628 institutes in 75 countries were included. There was an increase in publishing papers and citations each year. Most of the publications were authored by researchers from the United States and Italy. In the collaboration network map, Mayo Clinic, Karolinska Institute, the University of Washington had the largest cluster of nodes. Lagergren J, Corley DA, Whiteman DC, Vaughan TL, and Patti MG were the most prolific authors. There was a high concentration of research into bariatric surgery (BS), risk factors, body mass index (BMI), and Barrett's esophagus in this field. Future research may focus on weight gain, sleep apnea, sleeve gastrectomy (SG), and revisional bariatric surgery. Conclusions We summarized the research hotspots and trends, collaborative network, and future research directions in the field of obesity and GERD. In addition to help scholars understand essential information, our results will also enable them to identify research frontiers.

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GWAS meta-analysis of 16 790 patients with Barrett’s oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level

Cited by 9 publications

References 61 publications

Risk factors for eight common cancers revealed from a phenome-wide Mendelian randomisation analysis of 378,142 cases and 485,715 controls

Risk factors for eight common cancers revealed from a phenome-wide Mendelian randomisation analysis of 378,142 cases and 485,715 controls

Risk factors for eight common cancers revealed from a phenome-wide Mendelian randomisation analysis of 378,142 cases and 485,715 controls

A Bibliometric and Visual Analysis of Obesity and Gastroesophageal Reflux Disease

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