Incorporating medical interventions into carrier probability estimation for genetic counseling.
Incorporating medical interventions into carrier probability estimation for genetic counseling.
复制标题
DOI：
10.1186/1471-2350-8-13
复制
发表时间：
2007-03-22
影响因子：
--
通讯作者：
Katki HA
中科院分区：
文献类型：
--
作者：
Katki HA
根据家族病史预测谁可能携带已知疾病基因的遗传有害突变的孟德尔模型被用于各种临床和研究活动。接受遗传咨询的人越来越多地报告称，他们的家族史中有降低风险的医疗干预措施，因为最近，针对某些疾病的一系列预防性干预措施已经出现。例如，卵巢切除术降低了患乳腺癌和卵巢癌的风险，现在越来越多地向有乳腺癌和卵巢癌家族史的女性提供卵巢切除术。孟德尔模型应考虑医疗干预，因为干预会改变突变外显率，从而影响携带者概率估计。我们扩展了孟德尔模型来解释医疗干预，通过一个额外的因素来解释干预后的疾病历史，该因素可以从已发表的干预效果研究中估计出来。我们应用我们的方法将卵巢切除纳入BRCAPRO模型，该模型根据女性乳腺癌和卵巢癌的家族史预测其携带BRCA1和BRCA2突变的风险。这种新的BRCAPRO可用于临床。我们表明，考虑到家庭成员经历的干预会严重影响突变携带者概率估计，特别是如果家庭成员在干预后生活了多年。我们发现，由于干预的好处在运营商和非运营商之间的差异更大，所以干预对运营商概率的影响更大。这些发现意味着，不考虑医疗干预的携带者概率估计可能具有严重误导性，并可能影响临床医生关于提供基因检测的建议。BayesMendel软件允许人们实现任何孟德尔携带者概率模型，该软件已扩展到允许医疗干预，因此未来的孟德尔模型可以很容易地解释干预。
Mendelian models for predicting who may carry an inherited deleterious mutation of known disease genes based on family history are used in a variety of clinical and research activities. People presenting for genetic counseling are increasingly reporting risk-reducing medical interventions in their family histories because, recently, a slew of prophylactic interventions have become available for certain diseases. For example, oophorectomy reduces risk of breast and ovarian cancers, and is now increasingly being offered to women with family histories of breast and ovarian cancer. Mendelian models should account for medical interventions because interventions modify mutation penetrances and thus affect the carrier probability estimate. We extend Mendelian models to account for medical interventions by accounting for post-intervention disease history through an extra factor that can be estimated from published studies of the effects of interventions. We apply our methods to incorporate oophorectomy into the BRCAPRO model, which predicts a woman's risk of carrying mutations in BRCA1 and BRCA2 based on her family history of breast and ovarian cancer. This new BRCAPRO is available for clinical use. We show that accounting for interventions undergone by family members can seriously affect the mutation carrier probability estimate, especially if the family member has lived many years post-intervention. We show that interventions have more impact on the carrier probability as the benefits of intervention differ more between carriers and non-carriers. These findings imply that carrier probability estimates that do not account for medical interventions may be seriously misleading and could affect a clinician's recommendation about offering genetic testing. The BayesMendel software, which allows one to implement any Mendelian carrier probability model, has been extended to allow medical interventions, so future Mendelian models can easily account for interventions.
登录
查看更多内容
影响因子：
45.3
作者：
Domchek, SM;Eisen, A;Weber, BL
通讯作者：
Weber, BL
影响因子：
9.8
作者：
Parmigiani, G;Berry, DA;Aguilar, O
通讯作者：
Aguilar, O
影响因子：
4.7
作者：
Metcalfe, KA;Lynch, HT;Narod, SA
通讯作者：
Narod, SA
影响因子：
120.7
作者：
Chen, Sining;Wang, Wenyi;Parmigiani, Giovanni
通讯作者：
Parmigiani, Giovanni
影响因子：
5.7
作者：
Lauritzen, SL;Sheehan, NA
通讯作者：
Sheehan, NA