Pancreatic cancer surveillance: Risk stratification of individuals with a germline CDKN2A pathogenic variant.

IF 5.8 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

United European Gastroenterology Journal Pub Date : 2024-11-07 DOI:10.1002/ueg2.12662

Derk C F Klatte, Jihane Meziani, Djuna L Cahen, Merel van Diepen, Marco J Bruno, Monique E van Leerdam

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引用次数: 0

Abstract

Background: Individuals carrying a germline CDKN2A pathogenic variant (PV) are at a high risk of developing pancreatic ductal adenocarcinoma. Risk stratification could allow tailored surveillance.

Objective: To develop a Fine-Gray prediction model for the risk of PDAC in carriers of a CDKN2A PV.

Methods: Data from two large Dutch pancreatic cancer surveillance programs were used. A limited set of predictor variables were selected bsased on previous literature and the clinical expertise of the study group.

Results: A total of 506 CDKN2A PV carriers were included, among whom we showed a substantial lifetime risk of PDAC (23%). The model identifies having a first-degree relative with PDAC (B = 0.7256) and a history of smoking (B = 0.4776) as significant risk factors. However, the model shows limited discrimination (c-statistic 0.64) and calibration.

Conclusion: Our study highlights the high lifetime risk of PDAC in carriers of a CDKN2A PV. While identifying significant risk factors such as family history of PDAC and smoking, our prediction model shows limited precision, highlighting the need for additional factors such as biomarkers to improve its clinical utility for tailored surveillance of high-risk individuals.

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胰腺癌监测：对带有 CDKN2A 基因变异的个体进行风险分层。

背景：携带种系CDKN2A致病变异体（PV）的人罹患胰腺导管腺癌的风险很高。进行风险分层可实现有针对性的监测：目的：针对 CDKN2A PV 携带者罹患 PDAC 的风险建立 Fine-Gray 预测模型：方法：使用来自荷兰两个大型胰腺癌监测项目的数据。方法：采用荷兰两个大型胰腺癌监测项目的数据，根据以往文献和研究小组的临床专业知识，选择了一组有限的预测变量：结果：共纳入了 506 名 CDKN2A PV 携带者，我们发现他们终生罹患 PDAC 的风险很高（23%）。该模型发现，一级亲属患有 PDAC（B = 0.7256）和吸烟史（B = 0.4776）是重要的风险因素。然而，该模型显示出有限的区分度（c 统计量 0.64）和校准：我们的研究强调了 CDKN2A PV 携带者终生罹患 PDAC 的高风险。我们的预测模型在确定了 PDAC 家族史和吸烟等重要风险因素的同时，也显示出了有限的精确性，这突出表明需要生物标志物等其他因素来提高其临床实用性，以便对高风险个体进行有针对性的监测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

United European Gastroenterology Journal GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

10.50

自引率

13.30%

发文量

147

期刊介绍： United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.