Format

Send to

Choose Destination
Gastroenterology. 2018 Apr;154(5):1273-1281.e3. doi: 10.1053/j.gastro.2017.12.003. Epub 2017 Dec 13.

Determining Risk of Barrett's Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants.

Author information

1
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
2
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
3
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
4
Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Medicine, University of Queensland, Brisbane, Queensland, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
5
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
6
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
7
Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.
8
Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
9
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
10
Department of Oncology, Medical School, University of Sheffield, Sheffield, United Kingdom.
11
Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California.
12
Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas.
13
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina.
14
Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada.
15
Cancer Research UK, Cambridge Institute, Cambridge, United Kingdom.
16
Department of Oncology, University of Cambridge, Cambridge, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
17
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
18
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
19
Division of Epidemiology, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom.
20
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; School of Cancer Sciences, King's College London, London, United Kingdom.
21
Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
22
Division of Research, Kaiser Permanente Northern California, Oakland, California; San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, California.
23
Medical Research Council Cancer Unit, Hutchison-Medical Research Council Research Centre, University of Cambridge, Cambridge, United Kingdom.
24
Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
25
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.

Abstract

BACKGROUND & AIMS:

We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors.

METHODS:

We used pooled data from 3288 patients with BE, 2511 patients with EAC, and 2177 individuals without either (controls) from participants in the international Barrett's and EAC consortium as well as the United Kingdom's BE gene study and stomach and esophageal cancer study. We collected data on 23 genetic variants associated with risk for BE or EAC, and constructed a polygenic risk score (PRS) for cases and controls by summing the risk allele counts for the variants weighted by their natural log-transformed effect estimates (odds ratios) extracted from genome-wide association studies. We also collected data on demographic and lifestyle factors (age, sex, smoking, body mass index, use of nonsteroidal anti-inflammatory drugs) and symptoms of gastroesophageal reflux disease (GERD). Risk models with various combinations of non-genetic factors and the PRS were compared for their accuracy in identifying patients with BE or EAC using the area under the receiver operating characteristic curve (AUC) analysis.

RESULTS:

Individuals in the highest quartile of risk, based on genetic factors (PRS), had a 2-fold higher risk of BE (odds ratio, 2.22; 95% confidence interval, 1.89-2.60) or EAC (odds ratio, 2.46; 95% confidence interval, 2.07-2.92) than individual in the lowest quartile of risk based on PRS. Risk models developed based on only demographic or lifestyle factors or GERD symptoms identified patients with BE or EAC with AUC values ranging from 0.637 to 0.667. Combining data on demographic or lifestyle factors with data on GERD symptoms identified patients with BE with an AUC of 0.793 and patients with EAC with an AUC of 0.745. Including PRSs with these data only minimally increased the AUC values for BE (to 0.799) and EAC (to 0.754). Including the PRSs in the model developed based on non-genetic factors resulted in a net reclassification improvement for BE of 3.0% and for EAC of 5.6%.

CONCLUSIONS:

We used data from 3 large databases of patients from studies of BE or EAC to develop a risk prediction model based on genetic, clinical, and demographic/lifestyle factors. We identified a PRS that increases discrimination and net reclassification of individuals with vs without BE and EAC. However, the absolute magnitude of improvement is not sufficient to justify its clinical use.

KEYWORDS:

BEACON; Environmental Exposures; Neoplasm; SNP

PMID:
29247777
PMCID:
PMC5880715
[Available on 2019-04-01]
DOI:
10.1053/j.gastro.2017.12.003
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center