Statistical analyses of breast cancer risks for Australian BRCA1 and BRCA2 mutation carriers

大约10年前，两个名为BRCA1和BRCA2的基因被发现。这些基因的正常功能是防止乳腺癌和其他癌症的发展。所有人的每个基因都有两个副本，一个从他们的母亲那里遗传，一个从他们的父亲那里遗传。在一个副本中遗传缺陷的女性患乳腺癌和卵巢癌的风险更高。对于他们的实际癌症风险是什么，一直存在相当大的争议，特别是关于这些风险可能如何取决于他们的年龄。我们已经对此进行了研究，并开发了必要的统计方法，通过分析存在缺陷基因的家庭的数据来解决这些问题。在这项研究中，我们建议使用两项大型的澳大利亚研究，一项是多病例乳腺癌家庭(凯瑟琳·考宁安家族性乳腺癌研究联合会；kConFab)，另一项是通过维多利亚州和新南威尔士州癌症登记中心(澳大利亚乳腺癌家庭研究；ABCFS)选择的乳腺癌女性家庭，无论她们的家族癌症病史如何。已经进行了大量的工作来识别这些家族并测试它们在BRCA1和BRCA2中的故障。有超过350个家族携带缺陷，这使这项研究成为世界上最大的同类研究之一。我们将检查这些家庭的癌症病史，并确定哪些成员已经或可能继承了有缺陷的基因。然后，我们将准确地估计乳腺癌和卵巢癌的风险，而且比以前更精确。我们还将利用这些大型数据集开发一种简单的方法，根据她们的个人和家族癌症病史来确定哪些澳大利亚女性最有可能携带BRCA1或BRCA2缺陷。这项研究将帮助遗传咨询师向考虑进行BRCA1和BRCA2突变检测的澳大利亚女性告知她们的癌症风险，并帮助使乳腺癌遗传学更具成本效益。

About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. We have already conducted studies on this and have developed the necessary statistical methods to address these issues by analysing data from the families in which there are faulty genes. In this study we propose to use two large Australian studies, one of families with multiple-cases of breast cancer (Kathleen Cuningham Consortium for Research on Familial Breast Cancer; kConFab) and the other of the families of women with breast cancer chosen, irrespective of their family cancer histories, through the Victorian and NSW Cancer Registries (Australian Breast Cancer Family Study; ABCFS). A large amount of work has already been conducted to identify these families and test them for faults in BRCA1 and BRCA2. There are over 350 families who carry faults, making this one of the largest studies of its type in the world. We will check the cancer histories of these families and determine which members have, or are likely to have, inherited a faulty gene. We will then estimate the breast and ovarian cancer risks accurately, and with much more precision, than has been done previously. We will also use these large datasets to develop a simple method to identify which Australian women are most likely to carry a fault in BRCA1 or BRCA2, based on their personal and family cancer histories. This study will assist genetic counsellors inform Australian women who consider mutation testing for BRCA1 and BRCA2 about their cancer risks, and help make breast cancer genetics more cost effective.