28 research outputs found
Retinoblastoma: molecular genetics and clinical consequences
Meijers-Heijboer, E.J. [Promotor]Moll, A.C. [Promotor]Henneman, L. [Copromotor
The development of an online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making: a usability and pilot study
An online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making was developed. A two-phase usability test was conducted among 12 couples (N = 22; 2 persons participated without their partner) at risk for hereditary cancer and 15 health care providers. Couples and health care providers expressed similar suggestions for improvements, and evaluated the modified decision aid as acceptable, easy to use, and comprehensible. The final decision aid was pilot tested (N = 16) with paired sample t tests comparing main outcomes (decisional conflict, knowledge, realistic expectations regarding the reproductive options and decision self-efficacy) before (T0), immediately (T1) and 2 weeks after (T2) use of the decision aid. Pilot testing indicated decreased decisional conflict scores, increased knowledge, and improved realistic expectations regarding the reproductive options, at T1 and T2. No effect was found for couples’ decision self-efficacy. The positive findings during usability testing were thus reflected in the pilot study. The decision aid will be further evaluated in a nationwide pretest–posttest study to facilitate implementation in the onco-genetic counselling setting. Ultimately, it is expected that the decision aid will enable end-users to make an informed decision
Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands
Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel–Lindau disease (VHL), Li–Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mutation-positive families identified from the start of diagnostic testing until May 2013, and the number of PNDs performed for these syndromes within these families. Of 187 families with a known Rb-gene mutation, 22 had performed PND (11.8%), this was significantly higher than uptake for FAP (1.6%) and HBOC (<0.2%). For VHL (6.5%) and LFS (4.9%) the difference was not statistically significant. PND for Rb started 3 years after introduction of diagnostic DNA testing and remained stable over the years. For the other cancer syndromes PND started 10–15 years after the introduction and uptake for PND showed an increase after 2009. We conclude that uptake of PND for Rb was significantly higher than for FAP and HBOC, but not different from VHL and LFS. Early onset, high penetrance, lack of preventive surgery and perceived burden of disease may explain these differences
Reproductive decision-making in the context of hereditary cancer: the effects of an online decision aid on informed decision-making
Individuals having a genetic predisposition to cancer and their partners face challenging decisions regarding their wish to have children. This study aimed to determine the effects of an online decision aid to support couples in making an informed decision regarding their reproductive options. A nationwide pretest-posttest study was conducted in the Netherlands among 131 participants between November 2016 and May 2018. Couples were eligible for participation if one partner had a pathogenic variant predisposing for an autosomal dominant hereditary cancer syndrome. Participants completed a questionnaire before use (T0), and at 3 months (T3) after use of the decision aid to assess the primary outcome measure informed decision-making, and the secondary outcome measures decisional conflict, knowledge, realistic expectations, level of deliberation, and decision self-efficacy. T0–T3 comparisons show an overall positive effect for all outcome measures (all ps < 0.05; knowledge (ES = − 1.05), decisional conflict (ES = 0.99), participants’ decision self-efficacy (ES = −0.55), level of deliberation (ES = − 0.50), and realistic expectations (ES = − 0.44). Informed decision-making increased over time and 58.0% of the participants made an informed reproductive decision at T3. The online decision aid seems to be an appropriate tool to complement standard reproductive counseling to support our target group in making an informed reproductive decision. Use of the decision aid may lessen the negative psychological impact of decision-making on couples’ daily life and wellbeing
Reproductive decision-making in the context of hereditary cancer: the effects of an online decision aid on informed decision-making
Individuals having a genetic predisposition to cancer and their partners face challenging decisions regarding their wish to have children. This study aimed to determine the effects of an online decision aid to support couples in making an informed decision regarding their reproductive options. A nationwide pretest-posttest study was conducted in the Netherlands among 131 participants between November 2016 and May 2018. Couples were eligible for participation if one partner had a pathogenic variant predisposing for an autosomal dominant hereditary cancer syndrome. Participants completed a questionnaire before use (T0), and at 3 months (T3) after use of the decision aid to assess the primary outcome measure informed decision-making, and the secondary outcome measures decisional conflict, knowledge, realistic expectations, level of deliberation, and decision self-efficacy. T0-T3 comparisons show an overall positive effect for all outcome measures (allps < 0.05; knowledge (ES = - 1.05), decisional conflict (ES = 0.99), participants' decision self-efficacy (ES = -0.55), level of deliberation (ES = - 0.50), and realistic expectations (ES = - 0.44). Informed decision-making increased over time and 58.0% of the participants made an informed reproductive decision at T3. The online decision aid seems to be an appropriate tool to complement standard reproductive counseling to support our target group in making an informed reproductive decision. Use of the decision aid may lessen the negative psychological impact of decision-making on couples' daily life and wellbeing.Hereditary cancer genetic
Online decision support for persons having a genetic predisposition to cancer and their partners during reproductive decision-making
A nationwide pretest–posttest study was conducted in all clinical genetic centres in the
Netherlands, to evaluate the effects of an online decision aid to support persons who
have a genetic predisposition to cancer and their partners in making an informed decision
regarding reproductive options. Main outcomes (decisional conflict, knowledge, realistic
expectations, level of deliberation, and decision self‐efficacy) were measured before use
(T0), immediately after use (T1), and at 2 weeks (T2) after use of the decision aid. Paired
sample t tests were used to compute differences between the first and subsequent
measurements. T0–T1 and T0–T2 comparisons indicate a significant reduction in mean
decisional conflict scores with stronger effects for participants with high baseline deci‐
sional conflict. Furthermore, use of the decision aid resulted in increased knowledge levels and improved realistic expectations. Level of deliberation only increased for partici‐
pants with lower baseline levels of deliberation. Decision self‐efficacy increased for those
with low baseline scores, whereas those with high baseline scores showed a reduction at
T2. It can be concluded that use of the decision aid resulted in several positive outcomes
indicative of informed decision‐making. The decision aid is an appropriate and highly ap‐
preciated tool to be used in addition to reproductive counseling
The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at
increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether
the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.
Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events
are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers)
and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.
Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined
hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95%
CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated
with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers
were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2
mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there
was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95%
CI ¼ 0.54 to 0.98).
Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with
higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers
Retinoblastoma: molecular genetics and clinical consequences
promotiedatum: 11-2-2015 � prom-id: 972