Abstract
Abstract Background & Aims: We developed comprehensive risk prediction models for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) that incorporate a polygenic risk score (PRS) and non-genetic factors. Methods: We used pooled data from 3,288 BE, 2,511 EAC, and 2,177 controls from BEACON, the United Kingdom Barrett's Esophagus Gene Study, and United Kingdom Stomach and Oesophageal Cancer Study. A PRS was created from 23 BE/EAC risk loci. We developed and compared risk models with various combinations of non-genetics factors and the PRS. We assessed their predictive accuracy using the area under the receiver operating characteristic curve (AUC). Results: Individuals in the highest quartile of the PRS had 2-fold higher risks of BE (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.89-2.60) and EAC (OR, 2.46; 95% CI, 2.07-2.92) compared to those in the lowest quartile of the PRS. Risk models including only demographic/lifestyle factors (age, sex, smoking, body mass index, and nonsteroidal anti-inflammatory drugs) or only gastroesophageal reflux disease (GERD) symptoms had AUCs ranging from 0.637 to 0.667. The AUCs for models adding demographic/lifestyle factors to GERD symptoms were 0.793 and 0.745 for BE and EAC, respectively. Small absolute improvement in AUCs for each model was observed when including the PRS in the model (AUCs range, 0.656-0.799). Including the PRS in the model of non-genetic factors provided 3.0% and 5.6% improvement in the net reclassification index for BE and EAC, respectively. Conclusions: Although adding the PRS improved discrimination and net reclassification, the absolute magnitude of improvement is not sufficient to justify its clinical use. Citation Format: Jing Dong, Aaron Thrift. Risk prediction for Barrett's esophagus and esophageal adenocarcinoma: Incorporation of epidemiologic risk factors and 23 confirmed genetic loci [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2212.
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