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一种纳入生物标志物的病因预测模型,用于预测与职业性接触芳香胺相关的膀胱癌风险:一项初步研究。

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study.

作者信息

Mastrangelo Giuseppe, Carta Angela, Arici Cecilia, Pavanello Sofia, Porru Stefano

机构信息

Department of Cardiac, Thoracic, and Vascular Sciences, Unit of Occupational Medicine, University of Padova, Via Giustiniani 2 -, 35128 Padova, Italy.

Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, Brescia, Italy.

出版信息

J Occup Med Toxicol. 2017 Aug 8;12:23. doi: 10.1186/s12995-017-0167-4. eCollection 2017.

Abstract

BACKGROUND

No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines.

METHODS

Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; the area under the curve was used to evaluate discriminatory ability of models.

RESULTS

Area under the curve was 0.93 for the full model (including age, smoking and coffee habits, DNA adducts, 12 genotypes) and 0.86 for the short model (including smoking, DNA adducts, 3 genotypes). Using the "best cut-off" of predicted probability of a positive outcome, percentage of cases correctly classified was 92% (full model) against 75% (short model). Cancers classified as "positive outcome" are those to be referred for evaluation by an occupational physician for etiological diagnosis; these patients were 28 (full model) or 60 (short model). Using 3 genotypes instead of 12 can double the number of patients with suspect of aromatic amine related cancer, thus increasing costs of etiologic appraisal.

CONCLUSIONS

Integrating clinical, laboratory and genetic factors, we developed the first etiologic prediction model for aromatic amine related bladder cancer. Discriminatory ability was excellent, particularly for the full model, allowing individualized predictions. Validation of our model in external populations is essential for practical use in the clinical setting.

摘要

背景

目前尚无包含生物标志物的病因预测模型可用于预测与职业接触芳香胺相关的膀胱癌风险。

方法

研究对象为199例膀胱癌患者。临床、实验室和基因数据作为逻辑回归模型(完整模型和简化模型)的预测因子,其中因变量在15例与芳香胺相关的膀胱癌患者中为1,其他患者为0。采用受试者工作特征曲线法;曲线下面积用于评估模型的辨别能力。

结果

完整模型(包括年龄、吸烟和咖啡饮用习惯、DNA加合物、12种基因型)的曲线下面积为0.93,简化模型(包括吸烟、DNA加合物、3种基因型)的曲线下面积为0.86。使用阳性结果预测概率的“最佳截断值”,完整模型正确分类的病例百分比为92%,简化模型为75%。被分类为“阳性结果”的癌症患者应由职业医生进行病因诊断评估;这些患者在完整模型中有28例,在简化模型中有60例。使用3种基因型而非12种基因型会使疑似芳香胺相关癌症患者的数量增加一倍,从而增加病因评估成本。

结论

综合临床、实验室和基因因素,我们开发了首个与芳香胺相关的膀胱癌病因预测模型。辨别能力出色,尤其是完整模型,可实现个体化预测。在外部人群中验证我们的模型对于在临床环境中的实际应用至关重要。

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