Gietel-Habets J J G, de Die-Smulders C E M, Derks-Smeets I A P, Tibben A, Tjan-Heijnen V C G, van Golde R, Gomez-Garcia E, Kets C M, van Osch L A D M
Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands.
Hum Reprod. 2017 Mar 1;32(3):588-597. doi: 10.1093/humrep/dew352.
To what extent are BRCA mutation carriers and their partners in the Netherlands aware about preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) as reproductive options and what is their attitude towards these options?
Awareness of PGD (66%) and PND (61%) among BRCA mutation carriers and their partners is relatively high and 80% and 26%, respectively, of BRCA carriers and their partners find offering PGD and PND for hereditary breast and ovarian cancer (HBOC) acceptable.
Internationally, awareness of PGD among persons with a genetic cancer predisposition appears to be relatively low (35%) and although acceptability is generally high (71%), only a small proportion of mutation carriers would consider using PGD (36%). However, for HBOC, there are no studies available that investigated the perspective of individuals with a confirmed BRCA1/2 mutation and their partners about PGD and PND including demographic and medical correlates of awareness and acceptability.
STUDY DESIGN, SIZE, DURATION: A cross-sectional survey was completed by 191 participants between July 2012 and June 2013. Participants were recruited through patient organizations (88%) and the databases of two Clinical Genetics departments in the Netherlands (12%).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Male and female BRCA carriers and their partners completed an online survey, which assessed demographic and medical characteristics, and awareness, knowledge, acceptability and consideration of PGD and PND as main outcomes. Correlations between demographic and medical characteristics and the main outcomes were investigated.
The majority of respondents were female (87%), of reproductive age (86%) and about half reported a desire for a child in the future. About two-thirds (66%) were aware of PGD and 61% of PND for HBOC. PGD knowledge was moderate (5.5 on a 9-point scale) and acceptability of PGD and PND for HBOC was 80% and 26%, respectively. A minority would personally consider using PGD (39%) or PND (20%). Individuals with a higher educational level were more likely to be aware of PGD (P < 0.001) and PND (P < 0.001) and persons with a more immediate child wish were more often aware of PGD (P = 0.044) and had more knowledge about PGD (P = 0.001). PGD acceptability was positively associated with knowledge about PGD (P = 0.047), and PND acceptability was higher among partners in comparison to carriers (P = 0.001). Participants with a history of cancer and with a higher perceived seriousness of breast and ovarian cancer were more likely to consider using PGD (P = 0.003 and P < 0.001 respectively) or PND (P = 0.021 and P = 0.017 respectively).
LIMITATIONS, REASONS FOR CAUTION: The response rate (23%) of participants invited by the clinical genetics departments was low, probably related to a simultaneous study that used a similar recruitment strategy within the same target group, which may have resulted in selection bias. Moreover, PGD knowledge was measured with an instrument that is not yet validated since to date such an instrument is not available in the literature. Finally, the cross-sectional design of this study limits us from drawing any causal conclusions.
Improvement of information provision remains needed, in order to timely inform all couples with HBOC about the available reproductive options and enable them to make a balanced reproductive decision. This may limit the risk of negative psychological impact due to decisional conflict and possible regret.
STUDY FUNDING/COMPETING INTEREST(S): The Dutch breast cancer foundation Stichting Pink Ribbon (grant number 2010.PS11.C74). None of the authors have competing interests to declare.
Not applicable.
荷兰的BRCA突变携带者及其伴侣对植入前基因诊断（PGD）和产前诊断（PND）作为生殖选择的知晓程度如何，以及他们对这些选择持何种态度？
BRCA突变携带者及其伴侣中，对PGD（66%）和PND（61%）的知晓率相对较高，分别有80%的BRCA携带者及其伴侣认为为遗传性乳腺癌和卵巢癌（HBOC）提供PGD是可接受的，26%的人认为提供PND是可接受的。
在国际上，有遗传性癌症倾向的人群对PGD的知晓率似乎相对较低（35%），尽管接受度普遍较高（71%），但只有一小部分突变携带者会考虑使用PGD（36%）。然而，对于HBOC，尚无研究调查确诊为BRCA1/2突变的个体及其伴侣对PGD和PND的看法，包括知晓率和接受度的人口统计学及医学相关因素。
研究设计、规模、持续时间：2012年7月至2013年6月期间，191名参与者完成了一项横断面调查。参与者通过患者组织（88%）和荷兰两个临床遗传学部门的数据库（12%）招募。
参与者/材料、环境、方法：BRCA携带者及其伴侣（包括男性和女性）完成了一项在线调查，该调查评估了人口统计学和医学特征，以及作为主要结果的PGD和PND的知晓率、知识水平、接受度和考虑情况。研究了人口统计学和医学特征与主要结果之间的相关性。
大多数受访者为女性（87%），处于生育年龄（86%），约一半人表示未来想要孩子。约三分之二（66%）的人知晓HBOC的PGD，61%的人知晓PND。PGD知识水平中等（9分制下为5.5分），HBOC的PGD和PND接受度分别为80%和26%。少数人会亲自考虑使用PGD（39%）或PND（20%）。教育水平较高的个体更有可能知晓PGD（P<0.001）和PND（P<0.001），有更迫切生育愿望的人更常知晓PGD（P = 0.044）且对PGD有更多了解（P = 0.001）。PGD接受度与PGD知识呈正相关（P = 0.047），PND接受度在伴侣中高于携带者（P = 0.001）。有癌症病史且认为乳腺癌和卵巢癌严重性较高的参与者更有可能考虑使用PGD（分别为P = 0.003和P<0.001）或PND（分别为P = 0.021和P = 0.017）。
局限性、谨慎原因：临床遗传学部门邀请的参与者的回复率（23%）较低，可能与同时在同一目标群体中使用类似招募策略的另一项研究有关，这可能导致了选择偏倚。此外，PGD知识是用一种尚未经过验证的工具测量的，因为迄今为止文献中尚无此类工具。最后，本研究的横断面设计限制我们得出任何因果结论。
仍需要改进信息提供，以便及时告知所有HBOC夫妇可用的生殖选择，并使他们能够做出平衡的生殖决策。这可能会降低因决策冲突和可能的遗憾而产生负面心理影响的风险。
研究资金/利益冲突：荷兰乳腺癌基金会粉丝带基金会（资助编号2010.PS11.C74）。作者均无利益冲突声明。
不适用。
