Genetic Unit, Institute of Legal Medicine and Genomic Medicine Group, USC Faculty of Medicine, Spain.
Front Biosci (Landmark Ed). 2013 Jun 1;18(4):1358-72. doi: 10.2741/4185.
Breast cancer (BC) is a heterogeneous disease. The majority of breast cancer cases (about 70 percent) are considered sporadic. Familial breast cancer (about 30 percent of patients), often seen in families with a high incidence of BC, has been associated with a number of high-, moderate-, and low-penetrance susceptibility genes. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP1 (FANCJ), PALB2 (FANCN) and RAD51C (FANCO), are associated with moderate BC risk. Genome wide association studies (GWAS) in BC revealed a number of common low penetrance alleles associated with a slightly increased or decreased risk of BC. Currently, only high penetrance genes are used in clinical practice on a wide scale. Due to the development of next generation sequencing technologies, it is envisaged that all familial breast cancer genes will be included in the genetic test. However, additional research in clinical management of moderate and low-risk variants is needed before full implementation of multi-gene panel testing into clinical work-flows. In this review, we focus on the different components of familial breast cancer risk.
乳腺癌（BC）是一种异质性疾病。大多数乳腺癌病例（约 70%）被认为是散发性的。家族性乳腺癌（约 30%的患者）常发生在乳腺癌高发家族中，与多种高、中、低外显率易感基因有关。家族连锁研究已经确定了 BRCA1、BRCA2、PTEN 和 TP53 等高外显率基因，它们负责遗传性综合征。此外，基于家族和基于人群的综合方法表明，参与 DNA 修复的基因，如 CHEK2、ATM、BRIP1（FANCJ）、PALB2（FANCN）和 RAD51C（FANCO），与中度 BC 风险相关。BC 的全基因组关联研究（GWAS）揭示了许多常见的低外显率等位基因，与 BC 风险略有增加或降低相关。目前，只有高外显率基因在临床上广泛应用。由于下一代测序技术的发展，可以预见所有家族性乳腺癌基因都将包含在基因检测中。然而，在将多基因面板检测全面应用于临床工作流程之前，还需要对中度和低风险变异体的临床管理进行更多研究。在这篇综述中，我们重点介绍家族性乳腺癌风险的不同组成部分。
