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Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.
Dong, Jing; Maj, Carlo; Tsavachidis, Spiridon; Ostrom, Quinn T; Gharahkhani, Puya; Anderson, Lesley A; Wu, Anna H; Ye, Weimin; Bernstein, Leslie; Borisov, Oleg; Schröder, Julia; Chow, Wong-Ho; Gammon, Marilie D; Liu, Geoffrey; Caldas, Carlos; Pharoah, Paul D; Risch, Harvey A; May, Andrea; Gerges, Christian; Anders, Mario; Venerito, Marino; Schmidt, Thomas; Izbicki, Jakob R; Hölscher, Arnulf H; Schumacher, Brigitte; Vashist, Yogesh; Neuhaus, Horst; Rösch, Thomas; Knapp, Michael; Krawitz, Peter; Böhmer, Anne; Iyer, Prasad G; Reid, Brian J; Lagergren, Jesper; Shaheen, Nicholas J; Corley, Douglas A; Gockel, Ines; Fitzgerald, Rebecca C; Cook, Michael B; Whiteman, David C; Vaughan, Thomas L; Schumacher, Johannes; Thrift, Aaron P.
  • Dong J; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas; Division of Hematology and Oncology, Department of Medicine, Cancer Center, and Genomic Sciences & Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin.
  • Maj C; Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.
  • Tsavachidis S; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
  • Ostrom QT; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
  • Gharahkhani P; Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Anderson LA; Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland & Aberdeen Center for Health Data Science, University of Aberdeen, Scotland.
  • Wu AH; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Ye W; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Bernstein L; Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California.
  • Borisov O; Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.
  • Schröder J; Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
  • Chow WH; Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas.
  • Gammon MD; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina.
  • Liu G; Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada.
  • Caldas C; Cancer Research UK, Cambridge Institute, Cambridge, UK.
  • Pharoah PD; Department of Oncology, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Risch HA; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
  • May A; Department of Medicine II, Sana Klinikum, Offenbach, Germany.
  • Gerges C; Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
  • Anders M; Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Klinikum, Berlin, Germany.
  • Venerito M; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
  • Schmidt T; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
  • Izbicki JR; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
  • Hölscher AH; Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
  • Schumacher B; Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
  • Vashist Y; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
  • Neuhaus H; Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
  • Rösch T; Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
  • Knapp M; Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
  • Krawitz P; Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.
  • Böhmer A; Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
  • Iyer PG; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • Reid BJ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Lagergren J; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
  • Shaheen NJ; Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
  • Corley DA; Division of Research, Kaiser Permanente Northern California, Oakland, California; San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, California.
  • Gockel I; Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
  • Fitzgerald RC; Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK.
  • Cook MB; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
  • Whiteman DC; Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Vaughan TL; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Schumacher J; Center for Human Genetics, University Hospital of Marburg, Marburg, Germany.
  • Thrift AP; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas; Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas. Electronic address: aaron.thrift@bcm.edu.
Gastroenterology ; 159(6): 2065-2076.e1, 2020 12.
Article en En | MEDLINE | ID: mdl-32918910
ABSTRACT
BACKGROUND &

AIMS:

Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 61). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored.

METHODS:

Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits.

RESULTS:

We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, PBONF = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, PBONF = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals.

CONCLUSIONS:

The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esófago de Barrett / Neoplasias Esofágicas / Adenocarcinoma / Biomarcadores de Tumor / Predisposición Genética a la Enfermedad Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esófago de Barrett / Neoplasias Esofágicas / Adenocarcinoma / Biomarcadores de Tumor / Predisposición Genética a la Enfermedad Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Año: 2020 Tipo del documento: Article