Validation of the BOADICEA model in a prospective cohort of BRCA1/2 pathogenic variant carriers.

IF 3.5 2区医学 Q2 GENETICS & HEREDITY

Journal of Medical Genetics Pub Date : 2024-07-19 DOI:10.1136/jmg-2024-109943

Xin Yang, Thea M Mooij, Goska Leslie, Lorenzo Ficorella, Nadine Andrieu, Karin Kast, Christian F Singer, Anna Jakubowska, Carla H van Gils, Yen Y Tan, Christoph Engel, Muriel A Adank, Christi J van Asperen, Margreet G E M Ausems, Pascaline Berthet, Margriet J Collee, Jackie A Cook, Jacqueline Eason, Karin Y van Spaendonck-Zwarts, D Gareth Evans, Encarna B Gómez García, Helen Hanson, Louise Izatt, Zoe Kemp, Fiona Lalloo, Christine Lasset, Fabienne Lesueur, Hannah Musgrave, Sophie Nambot, Catherine Noguès, Jan C Oosterwijk, Dominique Stoppa-Lyonnet, Marc Tischkowitz, Vishakha Tripathi, Marijke R Wevers, Emily Zhao, Flora E van Leeuwen, Marjanka K Schmidt, Douglas F Easton, Matti A Rookus, Antonis C Antoniou

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引用次数: 0

Abstract

Background: No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in BRCA1/2 pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of BRCA1/2 PV carriers ascertained through clinical genetic centres.

Methods: We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 BRCA1 and 1365 BRCA2 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information.

Results: The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in BRCA1 or BRCA2 PV carriers. The full model identified 5.8%, 12.9% and 24.0% of BRCA1/2 PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options.

Conclusion: BOADICEA may be used to aid personalised cancer risk management and decision-making for BRCA1 and BRCA2 PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).

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在 BRCA1/2 致病变异携带者前瞻性队列中验证 BOADICEA 模型。

背景：迄今为止，BOADICEA多因素乳腺癌风险预测模型尚未专门针对BRCA1/2致病变异（PV）携带者进行过验证。在此，我们评估了 BOADICEA 在通过临床基因中心确定的 BRCA1/2 PV 携带者前瞻性队列中预测 5 年乳腺癌风险的性能：我们在由 1614 名 BRCA1 和 1365 名 BRCA2 PV 携带者（209 例病例）组成的前瞻性 TRANsIBCCS 队列研究中评估了模型校准和判别能力。研究参与者拥有生活方式、生殖、荷尔蒙、人体测量风险因素信息、基于 313 个 SNP 的多基因风险评分以及家族史信息：考虑了家族史和所有其他风险因素的全多因素模型总体校准良好（E/O=1.07，95% CI：0.92 至 1.24），预测风险的五分位数也校准良好。当考虑所有风险因素时，辨别能力达到最大（哈雷尔 C 指数=0.70，95% CI：0.67 至 0.74；曲线下面积=0.79，95% CI：0.76 至 0.82）。单独评估 BRCA1 或 BRCA2 PV 携带者时，模型性能相似。完整模型分别确定了 5.8%、12.9% 和 24.0% 的 BRCA1/2 PV 携带者的 5 年乳腺癌风险：BOADICEA 可用于帮助 BRCA1 和 BRCA2 PV 携带者进行个性化癌症风险管理和决策。它已在免费访问的 CanRisk 工具 (https://www.canrisk.org/) 中实施。

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

Journal of Medical Genetics 医学-遗传学

CiteScore

7.60

自引率

2.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.