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To establish whether existing mutation prediction models can identify which male breast cancer ( MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), BRCAPRO (BRCA probability) and the Myriad prevalence table ('Myriad'). These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed vs predicted carriers and assessed the Area Under the Receiver Operating Characteristic ( ROC) Curve ( AUC) for each model. BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% confidence interval [ CI]: [0.60-1.09] and 0.79, 95% CI: [0.57-1.09], vs. BRCAPRO: 1.02, 95% CI: [0.75-1.38] and 0.94, 95% CI: [0.68-1.31], respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671). BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources. [ABSTRACT FROM AUTHOR]

Approximately one million patients in the Netherlands and 27-36 million patients in Europe have one of the 5,000-8,000 known rare diseases. These patients often do not receive the care they need or with a substantial delay from diagnosis to treatment. As of March 2017, 24 European Reference Networks (ERNs) were launched with the aim to improve the care for these patients through cross-border healthcare, where in principle the knowledge travels and not the patient. It is expected that through the ERNs, European patients with a rare disease get more often and more quickly access to expert care and that it will accelerate guideline development and research. In each of the 24 ERNs, one or more Dutch expertise centres for rare diseases participate, and 5 ERNs are coordinated by centres from the Netherlands.

The Radboud University Medical Center was among the first to implement two-step exome sequencing in clinical genetic diagnostics. This study is the first to evaluate patient experiences with gene panels based on exome sequencing, using quantified psychological variables: acceptance, psychological distress, expectations of heredity and unsolicited findings. Between August 2011 and July 2012, 177 patients diagnosed with early-onset colorectal/kidney cancer, deafness, blindness or movement disorder consented to diagnostic exome sequencing offered by clinical geneticists. Baseline questionnaires were sent to 141 adults, returned by 111 with median age of 49 [22-79] years and positive family history in 81%. Follow-up included 91 responders at median 4 [2-22] weeks after results from known gene panels per diagnosis group; exome-wide analysis is ongoing. Confirmed or possibly pathogenic mutations were found in 31% with one unsolicited finding (oncogenetic panel). Most patients (92%) were satisfied. There were no significant changes in heredity-specific distress (18% at baseline, 17% at follow-up) and expectations of heredity. Fewer patients expected unsolicited findings at follow-up (29% vs 18%, p = 0.01). Satisfaction and distress were equal in those with vs without mutations. In conclusion, most adults accepted and were satisfied with gene panels based on diagnostic exome sequencing, few reporting distress., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Twelve to thirty % of colorectal cancer (CRC) patients and relatives with an increased familial risk of CRC are referred for preventive measures. New guidelines recommend genetic counselling for high-risk families and surveillance colonoscopy for moderate-risk families. Assessment of familial risk of CRC and referral rates for these preventive measures were determined 1 year after the introduction of new guidelines., Method: Assessment of familial risk of CRC and referral for preventive measures were measured in clinical practice among 358 patients with CRC in 18 hospitals using medical records and questionnaires. Additionally, a knowledge survey was performed among 312 clinicians., Results: Sixty-seven % of patients with an increased familial risk (n = 65/97) were referred for preventive measures, as were 23% (61/261) of low-risk patients. The uptake of genetic counselling in high-risk families was 33% (12/36). The uptake of surveillance colonoscopy in moderate-risk families was 34% (21/61). In the knowledge survey clinicians correctly determined familial risk in 55% and preventive measures in 65% of cases., Conclusion: Currently 67% of individuals with an increased familial risk of CRC were referred for preventive measures. Only one-third were referred in accordance with guidelines., (© 2013 The Authors. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.)

Background: The Dutch Health Council recently recommended the introduction of a colorectal cancer (CRC) screening programme by faecal occult blood testing (FOBT) for individuals aged 55-75 at population risk of CRC. Individuals at an increased familial CRC risk (≥ 2 times population risk) should be identified at a younger age, so they and their relatives can receive earlier, more intensive surveillance instead of FOBT., Aims: To determine the percentage of participants with a positive FOBT in a CRC screening programme with an increased familial CRC risk., Methods: In a population-based study, 10,569 individuals aged 50-75 received an FOBT. Individuals with a positive FOBT were invited for colonoscopy and familial risk assessment. Participants with an average familial CRC risk were compared to those with an increased risk. Increased familial CRC risk was defined as a cumulative lifetime risk of CRC of at least 10%., Results: Of 6001 participants, 430 had a positive FOBT, of whom 324 (63% males; mean age 63 years) completed colonoscopy and familial risk assessment. CRC (n=22) and/or advanced adenomas (n=122) were found in 133 participants. Familial CRC risk was increased in 6% of participants with a positive FOBT. No significant differences were found between participants with an average versus an increased familial CRC risk., Conclusion: Six percent of participants with a positive FOBT had an increased familial CRC risk. Identifying at-risk participants enables them and their relatives to undergo regular colonoscopies. Adding familial risk assessment to FOBT screening may thus prevent a substantial number of CRCs., (Copyright © 2011 Elsevier Ltd. All rights reserved.)