Clinical and Molecular Investigations of Familial Breast-Ovarian Cancer

在某些家庭中，乳腺癌和卵巢癌可能会同时发生。众所周知，BRCA1和BRCA2两个基因的缺陷会增加患乳腺癌和卵巢癌的风险，导致患有这两种癌症的家族(称为乳腺癌-卵巢癌家族)。来自BRCA1或BRCA2缺陷家族的个体可以接受基因测试，以确定他们是否有患癌症的风险。没有过错的人可以放心，有过错的人可以接受监测和/或预防性手术，以降低他们患癌症的风险。然而，大多数乳腺癌-卵巢癌家族并不是由于BRCA1或BRCA2的缺陷，目前几乎没有关于如何最好地管理它们的信息。我们招募了705个患有乳腺癌和卵巢癌的家庭，我将把这个数字增加到1300个家庭。我将调查BRCA1和BRCA2缺陷对这些家系的影响，看看新的乳腺癌易感基因ATM、CHEK2、BRIP1和PALB2是否在家族性乳腺癌-卵巢癌中起作用。通过分析家族中癌症聚集和基因缺陷的模式，我们将能够明确乳腺癌-卵巢癌家族中未受影响的亲属的癌症风险，这将使我们能够更好地在临床上对其进行管理。

Breast and ovarian cancer can occur together in some families. Faults in two genes, BRCA1 and BRCA2, are known to increase the risks of breast and ovarian cancer resulting in families with both cancers (known as breast-ovarian cancer families). Individuals from families with BRCA1 or BRCA2 faults can undergo gene testing to see if they are at-risk of cancer. Individuals without the fault are reassured and those with the fault can have surveillance and/or preventative surgery to reduce their risk of cancer. However, the majority of breast-ovarian cancer families are not due to faults in BRCA1 or BRCA2 and there is currently little information available on how to best manage them. We have recruited 705 families with breast-ovarian cancer and I shall increase this to 1300 families. I shall investigate the contribution of BRCA1 and BRCA2 faults to these families and will look to see if newer breast cancer susceptibility genes, ATM, CHEK2, BRIP1 and PALB2 have a role in familial breast-ovarian cancer. By analysing the patterns of cancer clustering and gene faults in the families we will be able to clarify the cancer risks to unaffected relatives in breast-ovarian cancer families, which will allow us to better manage them in clinic.