Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2
Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2
复制标题
DOI：
10.1086/301670
复制
发表时间：
1998-01-01
影响因子：
9.8
通讯作者：
Aguilar, O
中科院分区：
文献类型：
--
作者：
Parmigiani, G;Berry, DA;Aguilar, O
最近在人类基因组中发现了乳腺癌易感基因 BRCA1 和 BRCA2。携带这些基因之一突变的女性患乳腺癌和卵巢癌的几率大大增加，而且与正常人相比，她们患这种疾病的年龄通常要年轻得多。女性可以接受检测以确定她们是否是携带者。鉴于她的家族史，在测试前接受遗传咨询的女性可以得知她是携带者的可能性。在本文中，我们根据女性一级和二级亲属的乳腺癌和卵巢癌家族史，开发了一个模型，用于评估女性携带 BRCA1 和 BRCA2 突变的概率。特别重要的是患有癌症的家庭成员的关系、发病年龄以及未患癌症的家庭成员的年龄。这些信息可以在遗传咨询期间和基因检测之前获得。携带者概率是通过使用家族史作为证据并使用突变患病率作为先验分布从贝叶斯规则获得的。在解决个体携带者概率时，我们纳入了模型的一些关键输入的不确定性，例如特定年龄的疾病发病率和突变的总体患病率。有一些证据表明，其他未被发现的基因可能对解释家族性乳腺癌很重要。当前版本模型的用户应注意此限制。如果有关其他基因的数据可用，我们描述的方法可以扩展到两个以上的基因。
Breast cancer-susceptibility genes BRCA1 and BRCA2 have recently been identified on the human genome. Women who carry a mutation of one of these genes have a greatly increased chance of developing breast and ovarian cancer, and they usually develop the disease at a much younger age, compared with normal individuals. Women can be tested to see whether they are carriers. A woman who undergoes genetic counseling before testing can be told the probabilities that she is a carrier, given her family history. In this paper we develop a model for evaluating the probabilities that a woman is a carrier of a mutation of BRCA1 and BRCA2, on the basis of her family history of breast and ovarian cancer in first- and second-degree relatives. Of special importance are the relationships of the family members with cancer, the ages at onset of the diseases, and the ages of family members who do not have the diseases. This information can be elicited during genetic counseling and prior to genetic testing. The carrier probabilities are obtained from Bayes's rule, by use of family history as the evidence and by use of the mutation prevalences as the prior distribution, In addressing an individual's carrier probabilities, we incorporate uncertainty about some of the key inputs of the model, such as the age-specific incidence of diseases and the overall prevalence of mutations. There is some evidence that other, undiscovered genes may be important in explaining familial breast cancer. Users of the current version of the model should be aware of this limitation. The methodology that we describe can be extended to more than two genes, should data become available about other genes.