Meta-analysis of BRCA1 and BRCA2 penetrance
Meta-analysis of BRCA1 and BRCA2 penetrance
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DOI：
10.1200/jco.2006.09.1066
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发表时间：
2007-04-10
影响因子：
45.3
通讯作者：
Parmigiani, Giovanni
中科院分区：
文献类型：
--
作者：
Chen, Sining;Parmigiani, Giovanni
目的遗传咨询现在被常规地提供给携带BRCA1或BRCA2突变的高危个体。顾问提供的风险预测需要对突变外显率进行可靠的估计。世界各地的研究都对这种外显性进行了研究。报道的估计数字各不相同。为了促进高危人群的临床管理和咨询，我们通过荟萃分析来解决这一问题。方法我们对PubMed和选定的研究进行了文献搜索，这些研究具有不重叠的患者数据，包含基因分型信息，使用统计方法来解释确定，并以可用的格式报告风险。随后，我们使用德西蒙尼和莱尔德随机效应建模方法将已发表的估计值结合起来。观察到研究间的异质性。研究人群、突变类型、设计和估计方法似乎不是异质性的系统性来源。BRCA1基因突变携带者患乳腺癌的风险为57%(95%CI，47%~66%)，BRCA2基因突变携带者为49%(95%CI，40%~57%)；BRCA1基因突变携带者患卵巢癌的风险为40%(95%CI，35%~46%)，BRCA2基因突变携带者患卵巢癌的风险为18%(95%CI，13%~23%)。我们还报告了目前无症状携带者患癌症的潜在风险。结论本文提供了一组BRCA1和BRCA2突变携带者的风险估计，可供有兴趣基于一组综合研究而不是一项特定研究为患者提供建议的咨询师和临床医生使用。
PurposeGenetic counseling is now routinely offered to individuals at high risk of carrying a BRCA1 or BRCA2 mutation. Risk prediction provided by the counselor requires reliable estimates of the mutation penetrance. Such penetrance has been investigated by studies worldwide. The reported estimates vary. To facilitate clinical management and counseling of the at-risk population, we address this issue through a meta-analysis.MethodsWe conducted a literature search on PubMed and selected studies that had nonoverlapping patient data, contained genotyping information, used statistical methods that account for the ascertainment, and reported risks in a useable format. We subsequently combined the published estimates using the DerSimonian and Laird random effects modeling approach.ResultsTen studies were eligible under the selection criteria. Between-study heterogeneity was observed. Study population, mutation type, design, and estimation methods did not seem to be systematic sources of heterogeneity. Meta-analytic mean cumulative cancer risks for mutation carriers at age 70 years were as follows: breast cancer risk of 57% (95% CI, 47% to 66%) for BRCA1 and 49% ( 95% CI, 40% to 57%) for BRCA2 mutation carriers; and ovarian cancer risk of 40% ( 95% CI, 35% to 46%) for BRCA1 and 18% ( 95% CI, 13% to 23%) for BRCA2 mutation carriers. We also report the prospective risks of developing cancer for currently asymptomatic carriers.ConclusionThis article provides a set of risk estimates for BRCA1 and BRCA2 mutation carriers that can be used by counselors and clinicians who are interested in advising patients based on a comprehensive set of studies rather than one specific study.