Psychosocial Research Group, Prince of Wales Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
The University of Queensland Diamantina Institute, Dermatology Research Centre, University of Queensland, Brisbane, QLD, 4102, Australia.
Breast Cancer Res. 2020 Feb 17;22(1):21. doi: 10.1186/s13058-020-01260-3.
Polygenic factors are estimated to account for an additional 18% of the familial relative risk of breast cancer, with those at the highest level of polygenic risk distribution having a least a twofold increased risk of the disease. Polygenic testing promises to revolutionize health services by providing personalized risk assessments to women at high-risk of breast cancer and within population breast screening programs. However, implementation of polygenic testing needs to be considered in light of its current limitations, such as limited risk prediction for women of non-European ancestry. This article aims to provide a comprehensive review of the evidence for polygenic breast cancer risk, including the discovery of variants associated with breast cancer at the genome-wide level of significance and the use of polygenic risk scores to estimate breast cancer risk. We also review the different applications of this technology including testing of women from high-risk breast cancer families with uninformative genetic testing results, as a moderator of monogenic risk, and for population screening programs. Finally, a potential framework for introducing testing for polygenic risk in familial cancer clinics and the potential challenges with implementing this technology in clinical practice are discussed.
多基因因素据估计占乳腺癌家族相对风险的额外 18%，多基因风险分布最高的人群患病风险至少增加两倍。多基因检测有望通过为高乳腺癌风险的女性和人群乳腺癌筛查计划内的女性提供个性化风险评估来彻底改变医疗服务。然而，在考虑实施多基因检测时，需要考虑到其目前的局限性，例如对非欧洲血统女性的风险预测有限。本文旨在全面综述多基因乳腺癌风险的证据，包括在全基因组水平上发现与乳腺癌相关的变异以及使用多基因风险评分来估计乳腺癌风险。我们还综述了该技术的不同应用，包括对具有无信息遗传检测结果的高乳腺癌风险家族的女性进行检测、作为单基因风险的调节剂以及用于人群筛查计划。最后，讨论了在家族性癌症诊所中引入多基因风险检测的潜在框架以及在临床实践中实施该技术的潜在挑战。
