Sapkota Yadav
The Neurogenetics Laboratory, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Qld., Australia.
Cytogenet Genome Res. 2014;144(2):77-91. doi: 10.1159/000369045. Epub 2014 Nov 15.
Breast cancer is the most common cancer and the second leading cause of death in women worldwide. The disease is caused by a combination of genetic, environmental, lifestyle, and reproductive risk factors. Linkage and family-based studies have identified many pathological germline mutations, which account for around 20% of the genetic risk of familial breast cancer. In recent years, single nucleotide polymorphism-based genetic association studies, especially genome-wide association studies (GWASs), have been very successful in uncovering low-penetrance common variants associated with breast cancer risk. These common variants alone may explain up to an additional 30% of the familial risk of breast cancer. With the advent of available genetic resources and growing collaborations among researchers across the globe, the much needed large sample size to capture variants with small effect sizes and low population frequencies is being addressed, and hence many more common variants are expected to be discovered in the coming days. Here, major GWASs conducted for breast cancer predisposition and prognosis until 2013 are summarized. Few studies investigating other forms of genetic variations contributing to breast cancer predisposition and disease outcomes are also discussed. Finally, the potential utility of the GWAS-identified variants in disease risk models and some future perspectives are presented.
乳腺癌是全球女性中最常见的癌症，也是第二大死因。该疾病由遗传、环境、生活方式和生殖风险因素共同导致。连锁分析和基于家系的研究已鉴定出许多病理性种系突变，这些突变约占家族性乳腺癌遗传风险的20%。近年来，基于单核苷酸多态性的遗传关联研究，尤其是全基因组关联研究（GWAS），在揭示与乳腺癌风险相关的低 penetrance 常见变异方面非常成功。仅这些常见变异可能额外解释高达30%的家族性乳腺癌风险。随着可用遗传资源的出现以及全球研究人员之间日益增加的合作，捕获具有小效应大小和低人群频率变异所需的大样本量问题正在得到解决，因此预计在未来几天会发现更多常见变异。在此，总结了截至2013年针对乳腺癌易感性和预后进行的主要GWAS。还讨论了很少有研究调查导致乳腺癌易感性和疾病结局的其他形式的遗传变异。最后，介绍了GWAS鉴定的变异在疾病风险模型中的潜在效用以及一些未来展望。
