| 1. |
- Aad, G., et al.
(författare)
-
- 2015
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Waszak, S. M., et al.
(författare)
-
Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
- 2018
-
Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798
-
Tidskriftsartikel (refereegranskat)abstract
- Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 4069) and 5-year overall survival was 65% (95% CI 5281); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.
|
|
| 3. |
|
|
| 4. |
- Leppänen, M. H., et al.
(författare)
-
Physical activity intensity, sedentary behavior, body composition and physical fitness in 4-year-old children: results from the ministop trial
- 2016
-
Ingår i: International Journal of Obesity. - : NATURE PUBLISHING GROUP. - 0307-0565 .- 1476-5497. ; 40:7, s. 1126-1133
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Existing knowledge on associations of physical activity (PA) and sedentary behavior (SB) with body composition and physical fitness in preschoolers is limited. OBJECTIVE: To examine associations of PA and SB with body composition and physical fitness in healthy Swedish 4-year-old children. METHODS: We utilized baseline data collected in 2014 for the population-based MINISTOP trial (n = 307). Light-intensity PA (LPA), moderate-intensity PA (MPA), vigorous-intensity PA (VPA), moderate-to-vigorous PA (MVPA) and SB were measured using accelerometry (ActiGraph-wGT3x-BT). Body composition was measured using air-displacement plethysmography, and physical fitness (that is, cardiorespiratory fitness, lower and upper body muscular strength and motor fitness) was measured using the PREFIT fitness test battery. Multiple linear regression models adjusted for relevant confounders, and in addition, isotemporal substitution models were applied. RESULTS: Greater MVPA was associated with lower fat mass percent (%FM, P = 0.015), and greater VPA and MVPA were associated with higher fat-free mass index (FFMI, P = 0.002 and P = 0.011). In addition, greater VPA and MVPA were associated with higher scores for all physical fitness tests (P = 0.042 to Pamp;lt;0.001). The results for MVPA were primarily due to VPA. SB was associated with weaker handgrip strength (P = 0.031) when PA was not adjusted, but after adjusting also for VPA, the significant association disappeared (P = 0.25). Substituting 5 min per day of SB, LPA or MPA with 5 min per day of VPA was associated with higher FFMI and better scores for cardiorespiratory fitness and motor fitness. Correspondingly, substituting 5 min per day of VPA with SB or LPA was associated with weaker performance for lower muscular strength. CONCLUSIONS: Time spent on VPA was associated with higher FFMI and better physical fitness. The results suggest that promoting VPA may be important to improve childhood body composition and physical fitness already at an early age.
|
|
| 5. |
- Delisle Nyström, C., et al.
(författare)
-
Evaluation of the wrist-worn ActiGraph wGT3x-BT for estimating activity energy expenditure in preschool children
- 2017
-
Ingår i: European Journal of Clinical Nutrition. - : NATURE PUBLISHING GROUP. - 0954-3007 .- 1476-5640. ; 71:10, s. 1212-1217
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Easy-to-use and accurate methods to assess free-living activity energy expenditure (AEE) in preschool children are required. The aims of this study in healthy preschool children were to (a) evaluate the ability of the wrist-worn ActiGraph wGT3x-BT to predict free-living AEE and (b) assess wear compliance using a 7-day, 24-h protocol. SUBJECTS/METHODS: Participants were 40 Swedish children (5.5 +/- 0.2 years) in the Mobile-based intervention intended to stop obesity in preschoolers (MINISTOP) obesity prevention trial. Total energy expenditure (TEE) was assessed using the doubly labeled water method during 14 days. AEE was calculated as (TEEx0.9) minus predicted basal metabolic rate. The ActiGraph accelerometer was worn on the wrist for 7 days and outputs used were mean of the daily and awake filtered vector magnitude (mean VM total and mean VM waking). RESULTS: The ActiGraph was worn for 7 (n = 34, 85%), 6 (n = 4, 10%), 5 (n = 1, 2.5%) and 4 (n = 1, 2.5%) days (a valid day was. 600 awake minutes). Alone, mean VM total and mean VM waking were able to explain 14% (P = 0.009) and 24% (P = 0.001) of the variation in AEE, respectively. By incorporating fat and fat-free mass in the models 58% (mean VM total) and 62% (mean VM waking) in the variation of AEE was explained (P amp;lt; 0.001). CONCLUSIONS: The wrist-worn ActiGraph wGT3x-BT in combination with body composition variables explained up to the 62% of the variation in AEE. Given the high wear compliance, the wrist-worn ActiGraph has the potential to provide useful information in studies where physical activity in preschool children is measured.
|
|
| 6. |
- Nystrom, C. D., et al.
(författare)
-
Mobile-based intervention intended to stop obesity in preschool-aged children: the MINISTOP randomized controlled trial
- 2017
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 105:6, s. 1327-1335
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Traditional obesity prevention programs are time-and cost-intensive. Mobile phone technology has been successful in changing behaviors and managing weight; however, to our knowledge, its potential in young children has yet to be examined. Objective: We assessed the effectiveness of a mobile health (mHealth) obesity prevention program on body fat, dietary habits, and physical activity in healthy Swedish children aged 4.5 y. Design: From 2014 to 2015, 315 children were randomly assigned to an intervention or control group. Parents in the intervention group received a 6-mo mHealth program. The primary outcome was fat mass index (FMI), whereas the secondary outcomes were intakes of fruits, vegetables, candy, and sweetened beverages and time spent sedentary and in moderate-to-vigorous physical activity. Composite scores for the primary and secondary outcomes were computed. Results: No statistically significant intervention effect was observed for FMI between the intervention and control group (mean +/- SD: -0.23 +/- 0.56 compared with -0.20 +/- 0.49 kg/m(2)). However, the intervention group increased their mean composite score from baseline to follow-up, whereas the control group did not (+ 0.36 +/- 1.47 compared with -0.06 +/- 1.33 units; P = 0.021). This improvement was more pronounced among the children with an FMI above the median (4.11 kg/m(2)) (P = 0.019). The odds of increasing the composite score for the 6 dietary and physical activity behaviors were 99% higher for the intervention group than the control group (P = 0.008). Conclusions: This mHealth obesity prevention study in preschool-aged children found no difference between the intervention and control group for FMI. However, the intervention group showed a considerably higher postintervention composite score (a secondary outcome) than the control group, especially in children with a higher FMI. Further studies targeting specific obesity classes within preschool-aged children are warranted.
|
|
