Lanting Vincent, Oskam Merel, Wilmink Hanneke, Kamphuisen Pieter W, van Es Nick
Amsterdam UMC, University of Amsterdam, department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam.
Tergooi MC, department of Internal Medicine, Hilversum.
Curr Opin Hematol. 2025 May 1;32(3):138-145. doi: 10.1097/MOH.0000000000000861. Epub 2025 Jan 28.
Patients with cancer have an increased risk of venous thromboembolism (VTE). Guidelines suggest to use risk assessment tools to guide decisions about thromboprophylaxis, but current tools have modest discriminatory ability. Genetic information from the germline or tumor has the potential to improve VTE prediction. Here, we provide a clinical overview of the current role of genetics in cancer-associated VTE.
Germline mutations, such as factor V Leiden and prothrombin G20210A, are associated with a 2- to 2.5-fold increased VTE risk in patients with cancer. Tumor-specific somatic mutations also contribute to VTE risk, such as ALK rearrangements increasing the risk in nonsmall cell lung cancer and IDH1 mutations decreasing the risk in gliomas. Other somatic mutations associated with VTE independent of tumor type include KRAS , STK11 , MET , KEAP1 , CTNNB1 , and CDKN2B . Incorporating data on germline or somatic mutations in risk scores improves discriminatory ability compared with the Khorana score.
Specific germline and somatic mutations are associated with an increased VTE risk in patients with cancer and potentially improve performance of clinical risk scores. The increasing and widespread use of genetic testing in cancer care provides an opportunity for further development of prediction models incorporating genetic predictors.
癌症患者发生静脉血栓栓塞（VTE）的风险增加。指南建议使用风险评估工具来指导关于血栓预防的决策，但目前的工具鉴别能力有限。来自种系或肿瘤的遗传信息有可能改善VTE预测。在此，我们对遗传学在癌症相关VTE中的当前作用进行临床概述。
种系突变，如因子V莱顿突变和凝血酶原G20210A突变，与癌症患者VTE风险增加2至2.5倍相关。肿瘤特异性体细胞突变也会导致VTE风险，例如间变性淋巴瘤激酶（ALK）重排增加非小细胞肺癌的风险，异柠檬酸脱氢酶1（IDH1）突变降低神经胶质瘤的风险。其他与VTE相关且不依赖肿瘤类型的体细胞突变包括KRAS、丝氨酸/苏氨酸蛋白激酶11（STK11）、间质上皮转化因子（MET）、 Kelch样环氧氯丙烷相关蛋白1（KEAP1）、β-连环蛋白（CTNNB1）和细胞周期蛋白依赖性激酶抑制剂2B（CDKN2B）。与科纳纳评分相比，将种系或体细胞突变数据纳入风险评分可提高鉴别能力。
特定的种系和体细胞突变与癌症患者VTE风险增加相关，并有可能改善临床风险评分的性能。基因检测在癌症治疗中日益广泛的应用为进一步开发纳入基因预测指标的预测模型提供了机会。
