Sun Xiangqing, Elston Robert C, Barnholtz-Sloan Jill S, Falk Gary W, Grady William M, Faulx Ashley, Mittal Sumeet K, Canto Marcia, Shaheen Nicholas J, Wang Jean S, Iyer Prasad G, Abrams Julian A, Tian Ye D, Willis Joseph E, Guda Kishore, Markowitz Sanford D, Chandar Apoorva, Warfe James M, Brock Wendy, Chak Amitabh
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Cancer Epidemiol Biomarkers Prev. 2016 May;25(5):727-35. doi: 10.1158/1055-9965.EPI-15-0832. Epub 2016 Feb 29.
Barrett's esophagus is often asymptomatic and only a small portion of Barrett's esophagus patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with Barrett's esophagus. Familial aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the increased risk of esophageal adenocarcinoma for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well developed.
We developed a Barrett's Esophagus Translational Research Network (BETRNet) risk prediction model from 787 singly ascertained Barrett's esophagus pedigrees and 92 multiplex Barrett's esophagus pedigrees, fitting a multivariate logistic model that incorporates family history and clinical risk factors. The eight risk factors, age, sex, education level, parental status, smoking, heartburn frequency, regurgitation frequency, and use of acid suppressant, were included in the model. The prediction accuracy was evaluated on the training dataset and an independent validation dataset of 643 multiplex Barrett's esophagus pedigrees.
Our results indicate family information helps to predict Barrett's esophagus risk, and predicting in families improves both prediction calibration and discrimination accuracy.
Our model can predict Barrett's esophagus risk for anyone with family members known to have, or not have, had Barrett's esophagus. It can predict risk for unrelated individuals without knowing any relatives' information.
Our prediction model will shed light on effectively identifying high-risk individuals for Barrett's esophagus screening and surveillance, consequently allowing intervention at an early stage, and reducing mortality from esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 25(5); 727-35. ©2016 AACR.
巴雷特食管通常无症状,目前仅有一小部分巴雷特食管患者得到诊断并接受监测。因此,开发风险预测模型以识别巴雷特食管高危个体很重要。巴雷特食管和食管腺癌的家族聚集现象,以及有家族病史个体患食管腺癌风险的增加,凸显了在预测模型中纳入遗传因素的必要性。利用风险协变量和已确定的家族数据来确定风险预测模型的方法尚未得到充分发展。
我们从787个单一家系确诊的巴雷特食管家系和92个多个家系确诊的巴雷特食管家系中开发了一个巴雷特食管转化研究网络(BETRNet)风险预测模型,拟合了一个纳入家族史和临床风险因素的多变量逻辑模型。该模型纳入了八个风险因素,即年龄、性别、教育水平、父母状况、吸烟、烧心频率、反流频率和抑酸剂使用情况。在训练数据集和一个由643个多个家系确诊的巴雷特食管家系组成的独立验证数据集上评估预测准确性。
我们的结果表明家族信息有助于预测巴雷特食管风险,在家族中进行预测可提高预测校准度和判别准确性。
我们的模型可以为任何有已知患或未患巴雷特食管家庭成员的人预测巴雷特食管风险。它可以在不了解任何亲属信息的情况下为无亲属关系的个体预测风险。
我们的预测模型将有助于有效识别巴雷特食管筛查和监测的高危个体,从而实现早期干预,并降低食管腺癌死亡率。《癌症流行病学、生物标志物与预防》;25(5);727 - 35。©2016美国癌症研究协会。