Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus
Year: 2015
Type: review
Study design: Observational Study
Abstract: Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3-11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddv512
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Funders: Melanoma Research Alliance, Kaiser Permanente, Times Higher Education, Cancerfonden, National Institutes of Health, University of Texas MD Anderson Cancer Center, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1015137807, G169752262, G1842336688, RISK FACTORS FOR CANCER--ESOPHAGUS AND GASTRIC CARDIA, G293715275, Statistical Methods for Gene Environment Interactions In Lung Cancer, EPIDEMIOLOGY OF BARRETTS ESOPHAGUS, IKK Signals in Lymphocyte Physiology and Pathology, G4044608966, Epidemiology and Incidence of Barrett's Esophagus, Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study (BEAGESS), ETIOLOGY OF GASTRIC CARDIA/ESOPHAGEAL ADENOCARCINOMA, G5074211371, G5777246208, Barrett's Esophagus: Predictors of Progression, Genetic Predictors for DNA Repair Phenotype in CMM, G7093047072, G7151285313, G7219029022, ESTABLISHED INVESTIGATOR AWARD IN CANCER PREVENTION AND CONTROL, G8609168885, G88852782, G8913033980, Cancer Center Support Grant, G931623649, The University of Texas M. D. Anderson Cancer Center SPORE in Melanoma
OpenAlex ID: W2258087927