文章：

乳腺癌多基因风险评分在挪威人群中进行风险分层具有可行性

A Breast Cancer Polygenic Risk Score Is Feasible for Risk Stratification in the Norwegian Population

原文发布日期：16 August 2023

DOI: 10.3390/cancers15164124

类型: Article

开放获取: 是

英文摘要：

Background: Statistical associations of numerous single nucleotide polymorphisms with breast cancer (BC) have been identified in genome-wide association studies (GWAS). Recent evidence suggests that a Polygenic Risk Score (PRS) can be a useful risk stratification instrument for a BC screening strategy, and a PRS test has been developed for clinical use. The performance of the PRS is yet unknown in the Norwegian population. Aim: To evaluate the performance of PRS models for BC in a Norwegian dataset. Methods: We investigated a sample of 1053 BC cases and 7094 controls from different regions of Norway. PRS values were calculated using four PRS models, and their performance was evaluated by the area under the curve (AUC) and the odds ratio (OR). The effect of the PRS on the age of onset of BC was determined by a Cox regression model, and the lifetime absolute risk of developing BC was calculated using the iCare tool. Results: The best performing PRS model included 3820 SNPs, which yielded an AUC = 0.625 and an OR = 1.567 per one standard deviation increase. The PRS values of the samples correlate with an increased risk of BC, with a hazard ratio of 1.494 per one standard deviation increase (95% confidence interval of 1.406–1.588). The individuals in the highest decile of the PRS have at least twice the risk of developing BC compared to the individuals with a median PRS. The results in this study with Norwegian samples are coherent with the findings in the study conducted using Estonian and UK Biobank samples. Conclusion: The previously validated PRS models have a similar observed accuracy in the Norwegian data as in the UK and Estonian populations. A PRS provides a meaningful association with the age of onset of BC and lifetime risk. Therefore, as suggested in Estonia, a PRS may also be integrated into the screening strategy for BC in Norway.

摘要翻译： 

背景：全基因组关联研究已发现众多单核苷酸多态性与乳腺癌存在统计学关联。近期证据表明，多基因风险评分可作为乳腺癌筛查策略的有效风险分层工具，相关检测方法已开发并应用于临床。但该评分在挪威人群中的表现尚未明确。目的：评估多基因风险评分模型在挪威数据集中的乳腺癌预测效能。方法：我们分析了来自挪威不同地区的1053例乳腺癌患者及7094例对照样本。采用四种多基因风险评分模型计算风险值，通过曲线下面积和比值比评估模型性能。通过Cox回归模型确定多基因风险评分对乳腺癌发病年龄的影响，并利用iCare工具计算终生绝对发病风险。结果：包含3820个单核苷酸多态性的模型表现最佳，其曲线下面积为0.625，每增加一个标准差对应的比值比为1.567。样本的多基因风险评分值与乳腺癌风险升高相关，每增加一个标准差的风险比为1.494（95%置信区间为1.406-1.588）。与评分中位数组相比，评分最高十分位数组个体的乳腺癌发病风险至少增加两倍。本研究在挪威样本中的结果与爱沙尼亚及英国生物银行样本的研究结论一致。结论：既往验证的多基因风险评分模型在挪威数据中展现的准确度与在英国及爱沙尼亚人群中观察到的结果相似。该评分与乳腺癌发病年龄及终生风险存在显著关联。因此，正如爱沙尼亚的经验所示，多基因风险评分亦可纳入挪威的乳腺癌筛查策略。

原文链接：

A Breast Cancer Polygenic Risk Score Is Feasible for Risk Stratification in the Norwegian Population