Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Australia.
Curr Opin Genet Dev. 2010 Jun;20(3):315-23. doi: 10.1016/j.gde.2010.03.009. Epub 2010 Apr 22.
Multifactorial models developed for BRCA1/2 variant classification have proved very useful for delineating BRCA1/2 variants associated with very high risk of cancer, or with little clinical significance. Recent linkage of this quantitative assessment of risk to clinical management guidelines has provided a basis to standardize variant reporting, variant classification and management of families with such variants, and can theoretically be applied to any disease gene. As proof of principle, the multifactorial approach already shows great promise for application to the evaluation of mismatch repair gene variants identified in families with suspected Lynch syndrome. However there is need to be cautious of the noted limitations and caveats of the current model, some of which may be exacerbated by differences in ascertainment and biological pathways to disease for different cancer syndromes.
多因素模型的发展为 BRCA1/2 变体分类提供了非常有用的方法，可用于确定与癌症风险极高或临床意义不大的 BRCA1/2 变体相关的变体。最近，这种风险的定量评估与临床管理指南的联系为规范变体报告、变体分类和此类变体家族的管理提供了基础，并且从理论上讲，可以应用于任何疾病基因。作为原理的证明，多因素方法已经显示出在评估疑似林奇综合征家族中发现的错配修复基因变体方面具有很大的应用前景。然而，需要谨慎对待当前模型的注意到的局限性和警告，其中一些局限性可能会因不同癌症综合征的不同确定和疾病生物学途径而加剧。
