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Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

Publication ,  Journal Article
Dong, J; Maj, C; Tsavachidis, S; Ostrom, QT; Gharahkhani, P; Anderson, LA; Wu, AH; Ye, W; Bernstein, L; Borisov, O; Schröder, J; Chow, W-H ...
Published in: Gastroenterology
December 2020

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 6:1). 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.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.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.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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Published In

Gastroenterology

DOI

EISSN

1528-0012

ISSN

0016-5085

Publication Date

December 2020

Volume

159

Issue

6

Start / End Page

2065 / 2076.e1

Related Subject Headings

  • Sex Factors
  • Serine Endopeptidases
  • Risk Factors
  • Risk Assessment
  • RNA-Binding Proteins
  • Polymorphism, Single Nucleotide
  • Obesity
  • Male
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
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Dong, J., Maj, C., Tsavachidis, S., Ostrom, Q. T., Gharahkhani, P., Anderson, L. A., … Thrift, A. P. (2020). Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterology, 159(6), 2065-2076.e1. https://doi.org/10.1053/j.gastro.2020.08.052
Dong, Jing, Carlo Maj, Spiridon Tsavachidis, Quinn T. Ostrom, Puya Gharahkhani, Lesley A. Anderson, Anna H. Wu, et al. “Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.Gastroenterology 159, no. 6 (December 2020): 2065-2076.e1. https://doi.org/10.1053/j.gastro.2020.08.052.
Dong J, Maj C, Tsavachidis S, Ostrom QT, Gharahkhani P, Anderson LA, et al. Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterology. 2020 Dec;159(6):2065-2076.e1.
Dong, Jing, et al. “Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.Gastroenterology, vol. 159, no. 6, Dec. 2020, pp. 2065-2076.e1. Epmc, doi:10.1053/j.gastro.2020.08.052.
Dong J, Maj C, Tsavachidis S, Ostrom QT, Gharahkhani P, Anderson LA, Wu AH, Ye W, Bernstein L, Borisov O, Schröder J, Chow W-H, Gammon MD, Liu G, Caldas C, Pharoah PD, Risch HA, May A, Gerges C, Anders M, Venerito M, Schmidt T, Izbicki JR, Hölscher AH, Schumacher B, Vashist Y, Neuhaus H, Rösch T, Knapp M, Krawitz P, Böhmer A, Iyer PG, Reid BJ, Lagergren J, Shaheen NJ, Corley DA, Gockel I, Fitzgerald RC, Stomach and Oesophageal Cancer Study (SOCS) consortium, Cook MB, Whiteman DC, Vaughan TL, Schumacher J, Thrift AP. Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterology. 2020 Dec;159(6):2065-2076.e1.
Journal cover image

Published In

Gastroenterology

DOI

EISSN

1528-0012

ISSN

0016-5085

Publication Date

December 2020

Volume

159

Issue

6

Start / End Page

2065 / 2076.e1

Related Subject Headings

  • Sex Factors
  • Serine Endopeptidases
  • Risk Factors
  • Risk Assessment
  • RNA-Binding Proteins
  • Polymorphism, Single Nucleotide
  • Obesity
  • Male
  • Humans
  • Genome-Wide Association Study