Spatial clustering of childhood cancers in Switzerland Konstantinoudis, Garyfallos; Kreis, Christian; Ammann, Roland A. ...
CCC. Cancer causes & control/CCC, Cancer causes & control,
03/2018, Letnik:
29, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Purpose
Childhood cancers are rare and little is known about their etiology. Potential risk factors include environmental exposures that might implicate spatial variation of cancer risk. Previous ...studies of spatial clustering have mainly focused on childhood leukemia. We investigated spatial clustering of different childhood cancers in Switzerland using exact geocodes of place of residence.
Methods
We included 6,034 cancer cases diagnosed at age 0–15 years during 1985–2015 from the Swiss Childhood Cancer Registry. Age and sex-matched controls (10 per case) were randomly sampled from the national censuses (1990, 2000, 2010). Geocodes of place of residence were available at birth and diagnosis for both cases and controls. We used the difference in k-functions and Cuzick–Edwards test to assess global clustering and Kulldorff’s circular scan to detect individual clusters. We also carefully adjusted for multiple testing.
Results
After adjusting for multiple testing, we found no evidence of spatial clustering of childhood cancers neither at birth (
p
= 0.43) nor diagnosis (
p
= 0.13). Disregarding multiple testing, results of individual tests indicated spatial clustering of all childhood cancers combined (
p
< 0.01), childhood lymphoma (
p
= 0.01), due to Hodgkin lymphoma (HL) (
p
= 0.02) at diagnosis, and embryonal tumors of the central nervous system (CNS) at birth and diagnosis, respectively (
p
= 0.05 and
p
= 0.02).
Conclusions
This study provides weak evidence of spatial clustering of childhood cancers. Evidence was strongest for HL and embryonal CNS tumors, adding to the current literature that these cancers cluster in space.
We present the cytogenetic investigations of five histiocytic tumour lesions from children. In four cases there was a confirmed diagnosis of Langerhans cell histiocytosis (LCH) and one case of ...histiocytosis that did not fulfil all the criteria for true LCH. All five cases showed cytogenetic abnormalities, including the first report of an abnormal clone in LCH. The clone showed a t(7;12)(q11.2;p13) translocation and was detected in only a small percentage of cells. This case and a further three also contained non-clonal abnormalities and an increase in chromosome breakage. The fifth case, the only one in which no acquired abnormalities were seen, had a constitutional paracentric inversion of chromosome 13q.
PURPOSEAlthough most pediatric cancer patients survive, those who undergo anticancer treatments like chemotherapy and/or radiotherapy are at a high risk for late effects, such as cognitive deficits. ...To counteract these deficits, feasible and effective interventions are needed. The aim of this study was to compare the effects of working memory training, exergaming, and a wait-list control condition on cognitive functions in pediatric cancer survivors.
METHODSIn a parallel-group randomized trial, 69 pediatric cancer survivors aged 7–16 yr (mean = 11.35, SD = 3.53) were randomly assigned to 8-wk working memory training, exergaming, or a wait-list control group. Each training course consisted of three 45-min training sessions per week. The primary outcome comprised the core executive functions (visual working memory, inhibition, switching), and the secondary outcomes included other cognitive domains (intelligence, planning, memory, attention, processing speed), motor abilities, and parent rating on their children’s executive functions. Assessments were conducted both before and immediately after the interventions, and at 3-month follow-up.
RESULTSLinear mixed models revealed that participants in the working memory training group showed a linear improvement in visual working memory after training and at follow-up compared with the control group. No other intervention effects of either type of training could be detected.
CONCLUSIONThis study presents evidence that working memory training improves visual working memory in pediatric cancer survivors. Results show that near-transfer, but no far-transfer effects can be expected from working memory training. Multiple-component interventions tailored to fit the individual’s cognitive profile are needed to best support cognitive development after cancer and its treatment.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. During cell cycle progression from the mid- to late G1 phase, mammalian cells traverse the restriction point, a transition from ...mitogen dependence to mitogen independence, regulated by retinoblastoma protein (Rb). Different cyclin-dependent kinases (CDKs) sequentially phosphorylate and inactivate Rb, which is associated by a change in Rb's nuclear affinity and activation of E2F transcription. Here, we show by in vitro kinase assays that ALL extracts contained CDK2 catalytic activity. When liberation of Rb from cell nuclei was tested by immune precipitation of differential cell extractions and Western blot analysis, little Rb was associated with the nuclear compartment. Together with the immunocytochemical analysis at a single cell level that Rb was phosphorylated at serine 612 and threonine 821, sites known to be phosphorylated by CDK2, the data indicated the presence of CDK2 catalytic activity and loss of Rb's nuclear affinity in ALL cells. We conclude that most ALL cells reside at or beyond the restriction point. This could explain the resistance of ALL cells to differentiation induction.
Exposure to medium or high doses of ionizing radiation is a known risk factor for cancer in children. The extent to which low-dose radiation from natural sources contributes to the risk of childhood ...cancer remains unclear.
In a nationwide census-based cohort study, we investigated whether the incidence of childhood cancer was associated with background radiation from terrestrial gamma and cosmic rays.
Children < 16 years of age in the Swiss National Censuses in 1990 and 2000 were included. The follow-up period lasted until 2008, and incident cancer cases were identified from the Swiss Childhood Cancer Registry. A radiation model was used to predict dose rates from terrestrial and cosmic radiation at locations of residence. Cox regression models were used to assess associations between cancer risk and dose rates and cumulative dose since birth.
Among 2,093,660 children included at census, 1,782 incident cases of cancer were identified including 530 with leukemia, 328 with lymphoma, and 423 with a tumor of the central nervous system (CNS). Hazard ratios for each millisievert increase in cumulative dose of external radiation were 1.03 (95% CI: 1.01, 1.05) for any cancer, 1.04 (95% CI: 1.00, 1.08) for leukemia, 1.01 (95% CI: 0.96, 1.05) for lymphoma, and 1.04 (95% CI: 1.00, 1.08) for CNS tumors. Adjustment for a range of potential confounders had little effect on the results.
Our study suggests that background radiation may contribute to the risk of cancer in children, including leukemia and CNS tumors.
Purpose: This is the first study to quantify potential nonresponse bias in a childhood cancer survivor questionnaire survey. We describe early and late responders and nonresponders, and estimate ...nonresponse bias in a nationwide questionnaire survey of survivors.
Methods: In the Swiss Childhood Cancer Survivor Study, we compared characteristics of early responders (who answered an initial questionnaire), late responders (who answered after =1 reminder) and nonresponders. Sociodemographic and cancer-related information was available for the whole population from the Swiss Childhood Cancer Registry. We compared observed prevalence of typical outcomes in responders to the expected prevalence in a complete (100% response) representative population we constructed in order to estimate the effect of nonresponse bias. We constructed the complete population using inverse probability of participation weights.
Results: Of 2328 survivors, 930 returned the initial questionnaire (40%); 671 returned the questionnaire after =1reminder (29%). Compared to early and late responders, we found that the 727 nonresponders (31%) were more likely male, aged <20 years, French or Italian speaking, of foreign nationality, diagnosed with lymphoma or a CNS or germ cell tumor, and treated only with surgery. But observed prevalence of typical estimates (somatic health, medical care, mental health, health behaviors) was similar among the sample of early responders (40%), all responders (69%), and the complete representative population (100%). In this survey, nonresponse bias did not seem to influence observed prevalence estimates.
Conclusion: Nonresponse bias may play only a minor role in childhood cancer survivor studies, suggesting that results can be generalized to the whole population of such cancer survivors and applied in clinical practice.
The purpose of the present project was to analyse the costs incurred by the implementation of JACIE standards at a University Hospital with 1000 beds, performing some 40 autologous transplants per ...year. The cost analysis was performed on the basis of a prospective assessment of the time spent by all staff members involved with the implementation over a 14-month period of the quality management system (QMS) required by the JACIE standards. Two physicians worked on JACIE Section A (management=82 h), one physician and two nurses for section Ba (clinical unit adults=125.75 h), two physicians and three nurses for section Bp (clinical unit paediatrics=206 h), one physician, two nurses and one technician for section C (progenitor cell collection facility=105.75 h), and one physician and two technicians for section D (progenitor cell processing facility=426 h). The total time spent on the project amounted to 945.5 h with a total salary cost of \euro150 000. We concluded that implementation of the JACIE standards was accomplished within a 14-month period with a financial impact of approximately \euro150 000. The impact on quality parameters (eg clinical and laboratory end points, side effects) on HPC transplantation will be assessed in a second report after the first year of practical implementation.
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