The participation of minors in biobank research can offer great benefits for science and health care. However, as minors are a vulnerable population they are also in need of adequate protective... Show moreThe participation of minors in biobank research can offer great benefits for science and health care. However, as minors are a vulnerable population they are also in need of adequate protective measures when they are enrolled in research. Research using biobanked biological samples from children poses additional ethical issues to those raised by research using adult biobanks. For example, small children have only limited capacity, if any, to understand the meaning and implications of the research and to give a documented agreement to it. Older minors are gradually acquiring this capacity. We describe principles for good practice related to the inclusion of minors in biobank research, focusing on issues related to benefits and subsidiarity, consent, proportionality and return of results. Some of these issues are currently heavily debated, and we conclude by providing principles for good practice for policy makers of biobanks, researchers and anyone involved in dealing with stored tissue samples from children. Actual implementation of the principles will vary according to different jurisdictions. Show less
This study aims to give an overview of the number of prenatal tests for Huntington's disease (HD), test results, and pregnancy outcomes in the Netherlands between 1998 and 2008 and to compare them... Show moreThis study aims to give an overview of the number of prenatal tests for Huntington's disease (HD), test results, and pregnancy outcomes in the Netherlands between 1998 and 2008 and to compare them with available data from the period 1987-1997. A total of 126 couples underwent prenatal diagnosis (PND) on 216 foetuses: 185 (86%) direct tests and 31 (14%) exclusion tests. In 9% of direct tests the risk for the foetus was 25%. Four at-risk parents (4%) carried intermediate alleles. Ninety-one foetuses had CAG expansions ≥36 or 50% risk haplotypes: 75 (82%) were terminated for HD, 12 (13%) were carried to term; four pregnancies were miscarried, terminated for other reasons or lost to follow-up. Unaffected pregnancies (122 foetuses), resulted in the birth of 112 children. The estimated uptake of PND was 22% of CAG expansion carriers (≥36 repeats) at reproductive age. PND was used by two new subgroups: carriers of intermediate alleles, and 50% at-risk persons opting for a direct prenatal test of the foetus. A significant number of HD expansion or 50% risk pregnancies were continued. Speculations were made on causative factors contributing to these continuations. Further research on these couples' motives is needed. Show less
Euthanasia and physician-assisted suicide (PAS) by request and/or based on an advance directive are legal in The Netherlands under strict conditions, thus providing options for patients with... Show moreEuthanasia and physician-assisted suicide (PAS) by request and/or based on an advance directive are legal in The Netherlands under strict conditions, thus providing options for patients with Huntington's disease (HD) and other neurodegenerative diseases to stay in control and choose their end of life. HD is an inherited progressive disease characterised by chorea and hypokinesia, psychiatric symptoms and dementia. From a qualitative study based on interviews with 15 physicians experienced in treating HD, several ethical issues emerged. Consideration of these aspects leads to a discussion about the professional role of a physician in relation to the personal autonomy of a patient. Such a discussion can raise awareness that talking about end-of-life wishes with an HD patient is part of the legal, professional and moral responsibility of the physician, and that a letter of intent on behalf of the physician can improve active participation in the process. Discussion of these issues can help to advance the debate on euthanasia and PAS in HD and other neurodegenerative diseases. Show less
The outcome of bilateral prophylactic mastectomy with breast reconstruction (BPM-IBR) in healthy BRCA1/2 mutation carriers can be potentially burdensome for body image and the intimate relationship... Show moreThe outcome of bilateral prophylactic mastectomy with breast reconstruction (BPM-IBR) in healthy BRCA1/2 mutation carriers can be potentially burdensome for body image and the intimate relationship. Therefore, in the current analysis the impact on body image, sexual and partner relationship satisfaction was prospectively investigated in women opting for BPM-IBR as well as cancer distress and general quality of life. Healthy women undergoing BPM-IBR completed questionnaires preoperatively (T0, n = 48), at 6 months (T1, n = 44) and after finishing breast reconstruction (median 21 months, range 12-35) (T2, n = 36). With multi-level regression analyses the course of outcome variables was investigated and a statistically significant change in body image and/or sexual and partner relationship satisfaction was predicted by baseline covariates. Body image significantly decreased at T1. At T2 sexual relationship satisfaction and body image tended to be lower compared to baseline. The overall partner relationship satisfaction did not significantly change. At T2, 37 % of the women reported that their breasts felt unpleasantly, 29 % was not satisfied with their breast appearance and 21 % felt embarrassed for their naked body. Most body image issues remained unchanged in 30 % of the women. A negative body image was predicted by high preoperative cancer distress. BPM-IBR was associated with adverse impact on body image in a substantial subgroup, but satisfaction with the overall sexual and partner relationship did not significantly change in time. The psychosocial impact of BPM-IBR in unaffected women should not be underestimated. Psychological support should ideally be integrated both before and after BPM-IBR. Show less
OBJECTIVE To examine the frequency and correlates of skin examination behaviors in an international sample of individuals at varying risk of developing melanoma. DESIGN A cross-sectional, web-based... Show moreOBJECTIVE To examine the frequency and correlates of skin examination behaviors in an international sample of individuals at varying risk of developing melanoma. DESIGN A cross-sectional, web-based survey. SETTING Data were collected from the general population over a 20-month period on behalf of the Melanoma Genetics Consortium (GenoMEL). PARTICIPANTS A total of 8178 adults from Northern (32%), Central (33%), and Southern (14%) Europe, Australia (13%), and the United States (8%). MAIN OUTCOME MEASURES Self-reported frequency of skin self-examination (SSE) and clinical skin examination (CSE). RESULTS After adjustment for age and sex, frequency of skin examination was higher in both Australia (odds ratio [OR]SSE=1.80 [99% CI, 1.49-2.18]; ORCSE=2.68 [99% CI, 2.23-3.23]) and the United States (ORSSE=2.28 [99% CI, 1.76-2.94]; ORCSE=3.39 [99% CI, 2.60-4.18]) than in the 3 European regions combined. Within Europe, participants from Southern Europe reported higher rates of SSE than those in Northern Europe (ORSSE=1.61 [99% CI, 1.31-1.97]), and frequency of CSE was higher in both Central (ORCSE=1.47 [99% CI, 1.22-1.78]) and Southern Europe (ORCSE=3.46 [99% CI, 2.78, 4.31]) than in Northern Europe. Skin examination behavior also varied according to melanoma history: participants with no history of melanoma reported the lowest levels of skin examination, while participants with a previous melanoma diagnosis reported the highest levels. After adjustment for region, and taking into account the role of age, sex, skin type, and mole count, engagement in SSE and CSE was associated with a range of psychosocial factors, including perceived risk of developing melanoma; perceived benefits of, and barriers to, skin examination; perceived confidence in one's ability to engage in screening; and social norms. In addition, among those with no history of melanoma, higher cancer-related worry was associated with greater frequency of SSE. CONCLUSIONS Given the strong association between psychosocial factors and skin examination behaviors, particularly among people with no history of melanoma, we recommend that greater attempts be made to integrate psycho-education into the fabric of public health initiatives and clinical care, with clinicians, researchers, and advocacy groups playing a key role in guiding individuals to appropriate tools and resources. Show less
Individuals at risk for developing hereditary cancer are offered surveillance in order to improve the prognosis. An important question is whether the benefit of surveillance outweighs the... Show moreIndividuals at risk for developing hereditary cancer are offered surveillance in order to improve the prognosis. An important question is whether the benefit of surveillance outweighs the psychological burden. In this review, we evaluated all studies that investigated psychological distress and the quality of life in individuals under surveillance for hereditary cancer of the breast, ovarian, prostate, pancreas, colorectum, melanoma, and various rare syndromes such as familial adenomatous polyposis, Li-Fraumeni and Peutz-Jeghers syndrome. Thirty-two studies were identified. Surveillance for most hereditary cancers was associated with good psychological outcomes. However, surveillance of individuals at high risk for developing multiple tumors appeared to be associated with increased distress and a lower quality of life. Common factors associated with worse psychological outcomes included a personal history of cancer, female gender, having a first degree relative with cancer, negative illness perceptions and coping style. The use of a simple screening tool to identify distressed individuals is recommended. Show less
Huntington's disease (HD) is known to have a negative impact on family life. Offspring of HD patients may be exposed to adversity in childhood because of the parent's disease and its psychological... Show moreHuntington's disease (HD) is known to have a negative impact on family life. Offspring of HD patients may be exposed to adversity in childhood because of the parent's disease and its psychological consequences. BRCA1/2 hereditary breast and ovarian cancer (BRCA1/2) increases the risk for offspring of being exposed to parental disease or loss. Childhood adversity is associated with psychopathology and various other problems in later life. Adverse childhood experiences (ACEs) before age 16 were assessed in adults at 50% risk for HD (n = 74) or BRCA1/2 (n = 82) and in controls (n = 101), using the Negative Life Events Scale. Mean number and occurrence of ACEs were compared between groups. The odds of having experienced adversity in childhood were higher in HD offspring and BRCA1/2 offspring than in controls. HD offspring reported a higher mean number of ACEs than controls or BRCA1/2 offspring. In HD offspring, the prevalence of parental disease and parental dysfunction experienced before age 16 was higher than in controls. In BRCA1/2 offspring, the prevalence of parental loss before age 16 was higher than in controls. This study indicates that 53% of HD offspring and 45% of BRCA1/2 offspring are exposed to adversity in childhood or adolescence. The relevance of these findings for counseling in predictive testing programs, reproductive decision-making, and child rearing matters is discussed. Show less
OBJECTIVE: Previous studies suggest that learning a DNA-test-result has no direct impact on the medical-decisions and psychological well-being of counselees. Their perception, especially their... Show moreOBJECTIVE: Previous studies suggest that learning a DNA-test-result has no direct impact on the medical-decisions and psychological well-being of counselees. Their perception, especially their recollections and interpretations of their cancer-risks and heredity, predict and/or mediate this impact. These studies were criticized for their small range of predictors, mediators, outcomes and contextual factors. We studied the short-term impact of DNA-testing with an extended model. METHODS: Three months after disclosure of BRCA1/2-test-results, we sent counselees a questionnaire about their perception, medical and psychological outcomes, and medical, familial and psychological contexts. 248 affected women participated; 30 had received pathogenic-mutations, 16 unclassified-variants and 202 uninformative-results. RESULTS: The actually communicated genetic-information and the contextual variables predicted the counselees' perception, but did not directly predict any outcomes. The counselees' perception predicted and/or completely mediated the counselees' medical intentions and behavior, physical and psychological life-changes, stigma, mastery, negativity and cancer-worries. Short-term distress was related to the perception not only of their own risks, but also of their relatives' risks and heredity-likelihood. Effect sizes were medium to large. CONCLUSIONS AND IMPLICATIONS: The outcomes of DNA-testing were better predicted by the counselees' perception than by the actually given genetic-information. We recommend genetic-counselors to have tailored, interactive dialogues about the counselees' perception. Show less
Heijer, M. den; Seynaeve, C.; Vanheusden, K.; Duivenvoorden, H.J.; Vos, J.; Bartels, C.C.M.; ... ; Tibben, A. 2011
Purpose: Genetic counseling may help counselees understand their genetic risk of developing breast/ovarian cancer. However, many studies have shown that their perception of their risks is... Show morePurpose: Genetic counseling may help counselees understand their genetic risk of developing breast/ovarian cancer. However, many studies have shown that their perception of their risks is inaccurate. Information-oriented variables often predicted the level of accuracy, focusing on specific processes of receiving and processing risks. We examined counselee-oriented predictors about how counselees embed cancer risks in their lives. These predictors reflect the personal meaning of genetic risks and are expected to explain/mediate the impact of genetic counseling on risk-perception-accuracy. Method: We analyzed 248 questionnaires of a prospective study, filled in by probands with breast/ovarian cancer and pathogenic mutations, unclassified variants, or uninformative results (n = 30, 16, and 202, respectively). Mediation regression analyses were performed to examine whether counselee predictors mediated/explained the influence of information predictors on the accuracy. Information-oriented predictors regarded presentation format, communicated information, question format, education, pedigree information, cancer experience, and cognitive processes/heuristics. Counselee-oriented predictors regarded their self/personality, life/existence, and need for certainty about DNA test result, heredity, and cancer. Results: Both information-oriented and counselee-oriented variables significantly predicted the accuracy of the counselees' risk perception, with moderate to large effect sizes. Counselee-oriented variables completely mediated/explained the effects of information-oriented variables on the accuracy. Discussion: Counselees seemed to transform objective cancer risks into personally relevant information. Only through this personal meaning of genetic information, information-oriented processes seemed to cause inaccurate perceptions. Genetic counselors are suggested to focus communication on these personal processes. Genet Med 2011:13(9):800-811. Show less
