Jing Dong, Matthew F. Buas, Puya Gharahkhani, Bradley J. Kendall, Lynn Onstad, Shanshan Zhao, Lesley A. Anderson, Anna H. Wu, Weimin Ye, Nigel C. Bird, Leslie Bernstein, Wong-Ho Chow, Marilie D. Gammon, Geoffrey Liu, Carlos Caldas, Paul D. Pharoah, Harvey A. Risch, Prasad G. Iyer, Brian J. Reid, Laura J. Hardie, Jesper Lagergren, Nicholas J. Shaheen, Douglas A. Corley, Rebecca C. Fitzgerald, Stomach and Oesophageal Cancer Study consortium, David C. Whiteman, Thomas L. Vaughan, Aaron P. Thrift
Abstract
We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors.
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.
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%.
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.
Pharmacology, Toxicology and Pharmaceutical Science
2
2%
Other
8
9%
Unknown
41
46%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 May 2018.
All research outputs
#3,365,108
of 25,930,027 outputs
Outputs from Gastroenterology
#2,751
of 12,418 outputs
Outputs of similar age
#68,718
of 447,243 outputs
Outputs of similar age from Gastroenterology
#43
of 163 outputs
Altmetric has tracked 25,930,027 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,418 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.9. This one has done well, scoring higher than 77% of its peers.
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We're also able to compare this research output to 163 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
