Heinz Hengartner

Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study

Background Previous studies on childhood cancer and nuclear power plants (NPPs) produced conflicting results. We used a cohort approach to examine whether residence near NPPs was associated with leukaemia or any childhood cancer in Switzerland. Methods We computed person-years at risk for children aged 0–15 years born in Switzerland from 1985 to 2009, based on the Swiss censuses 1990 and 2000 and identified cancer cases from the Swiss Childhood Cancer Registry. We geo-coded place of residence at birth and calculated incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing the risk of cancer in children born <5 km, 5–10 km and 10–15 km from the nearest NPP with children born >15 km away, using Poisson regression models. Results We included 2925 children diagnosed with cancer during 21 117 524 person-years of follow-up; 953 (32.6%) had leukaemia. Eight and 12 children diagnosed with leukaemia at ages 0–4 and 0–15 years, and 18 and 31 children diagnosed with any cancer were born <5 km from a NPP. Compared with children born >15 km away, the IRRs (95% CI) for leukaemia in 0–4 and 0–15 year olds were 1.20 (0.60–2.41) and 1.05 (0.60–1.86), respectively. For any cancer, corresponding IRRs were 0.97 (0.61–1.54) and 0.89 (0.63–1.27). There was no evidence of a dose–response relationship with distance (P > 0.30). Results were similar for residence at diagnosis and at birth, and when adjusted for potential confounders. Results from sensitivity analyses were consistent with main results. Conclusions This nationwide cohort study found little evidence of an association between residence near NPPs and the risk of leukaemia or any childhood cancer.

The prognostic significance of cytogenetic aberrations in childhood acute myeloid leukaemia. A study of the Swiss Paediatric Oncology Group (SPOG)

In childhood‐onset acute myeloid leukaemia (AML) the clinical value of karyotypic aberrations is now acknowledged, although there is still debate concerning the prognostic significance of some events. To add to this knowledge, cytogenetic analysis was performed on a consecutive series of 84 childhood AML patients diagnosed in Switzerland. A result was obtained for all patients, with 69 (82%) showing a clonal karyotypic aberration. In the remaining 15 (18%), no karyotypic aberration was seen by either conventional or fluorescence in situ hybridisation analyses. The most frequent aberrations observed were t(11q23) (19% of all patients), t(8;21) (12%) and +8 (11%). Except for cytogenetics, no clinical parameter was shown to be significantly associated with outcome. The analysis of individual cytogenetic subgroups demonstrated that aberrations involving chromosome 16q were the strongest predictor of a good prognosis, while +8 and complex karyotypes represented the strongest predictors of a poor prognosis. It was also noteworthy that patients with the rare aberrations of del(11q) (n = 4) and t(16;21)(p11;q22) (n = 3) had a poor outcome. The results support the importance of cytogenetic analysis in childhood AML, but show that further work is required in the classification of the poor prognosis aberrations.

Alcohol consumption and binge drinking in young adult childhood cancer survivors.

This study compared frequency of alcohol consumption and binge drinking between young adult childhood cancer survivors and the general population in Switzerland, and assessed its socio‐demographic and clinical determinants.

Space‐time clustering of childhood cancers in Switzerland: A nationwide study

The aetiology of childhood cancers remains largely unknown. It has been hypothesized that infections may be involved and that mini‐epidemics thereof could result in space‐time clustering of incident cases. Most previous studies support spatio‐temporal clustering for leukaemia, while results for other diagnostic groups remain mixed. Few studies have corrected for uneven regional population shifts which can lead to spurious detection of clustering. We examined whether there is space‐time clustering of childhood cancers in Switzerland identifying cases diagnosed at age <16 years between 1985 and 2010 from the Swiss Childhood Cancer Registry. Knox tests were performed on geocoded residence at birth and diagnosis separately for leukaemia, acute lymphoid leukaemia (ALL), lymphomas, tumours of the central nervous system, neuroblastomas and soft tissue sarcomas. We used Bakers Max statistic to correct for multiple testing and randomly sampled time‐, sex‐ and age‐matched controls from the resident population to correct for uneven regional population shifts. We observed space‐time clustering of childhood leukaemia at birth (Bakers Max p = 0.045) but not at diagnosis (p = 0.98). Clustering was strongest for a spatial lag of <1 km and a temporal lag of <2 years (Observed/expected close pairs: 124/98; p Knox test = 0.003). A similar clustering pattern was observed for ALL though overall evidence was weaker (Bakers Max p = 0.13). Little evidence of clustering was found for other diagnostic groups (p > 0.2). Our study suggests that childhood leukaemia tends to cluster in space‐time due to an etiologic factor present in early life.

Non-classical karyotypic features in relapsed childhood B-cell precursor acute lymphoblastic leukemia

Karyotype analysis of acute lymphoblastic leukemia (ALL) at diagnosis has provided valuable prognostic markers for treatment stratification. However, reports of cytogenetic studies of relapsed ALL samples are limited. We compared the karyotypes from 436 nonselected B-cell precursor ALL patients at initial diagnosis and of 76 patients at first relapse. We noticed a relative increase of karyotypes that did not fall into the classic ALL cytogenetic subgroups (high hyperdiploidy, t(12;21), t(9;22), 11q23, t(1;19), <45 chromosomes) in a group of 29 patients at relapse (38%) compared to 130 patients at presentation (30%). Non-classical cytogenetic aberrations in these 29 patients were mostly found on chromosomes 1, 2, 7, 9, 13, 14, and 17. We also describe six rare reciprocal translocations, three of which involved 14q32. The most frequent abnormalities were found in 9p (12/29 cases) and were associated with a marked decrease in the duration of the second remission, but not of the probability of 10-year event-free survival after relapse treatment. From 29 patients with non-classical cytogenetic aberrations, only 8 (28%) had been stratified to a high risk-arm on the first treatment protocol, suggesting that this subgroup might benefit from the identification of new prognostic markers in future studies.

Compound Heterozygosity for Hb S [β6(A3)Glu→Val, GAG→GTG] and a New Thalassemic Mutation [β132(H10)Lys→Term, AAA→TAA] Detected in a Family from West Africa

We describe a Hb S/β-thalassemia (β-thal) mutation involving an A→T transition at codon 132 of the β-globin gene. The mutation, in the heterozygous state, unlike several other mutations in exon 3, shows no signs of dominant thalassemia but those of a typical β0 carrier. Compound heterozygosity with Hb S [β6(A3)Glu→Val, GAG→GTG] showed a severe clinical picture.

Parents’ and Physicians’ Perceptions of Children’s Participation in Decision-making in Paediatric Oncology: A Quantitative Study

The goal is to present how shared decision-making in paediatric oncology occurs from the viewpoints of parents and physicians. Eight Swiss Pediatric Oncology Group centres participated in this prospective study. The sample comprised a parent and physician of the minor patient (<18 years). Surveys were statistically analysed by comparing physicians’ and parents’ perspectives and by evaluating factors associated with children’s actual involvement. Perspectives of ninety-one parents and twenty physicians were obtained for 151 children. Results indicate that for six aspects of information provision examined, parents’ and physicians’ perceptions differed. Moreover, parents felt that the children were more competent to understand diagnosis and prognosis, assessed the disease of the children as worse, and reported higher satisfaction with decision-making on the part of the children. A patient’s age and gender predicted involvement. Older children and girls were more likely to be involved. In the decision-making process, parents held a less active role than they actually wanted. Physicians should take measures to ensure that provided information is understood correctly. Furthermore, they should work towards creating awareness for systematic differences between parents and physicians with respect to the perception of the child, the disease, and shared decision-making.

Characterization of high-hyperdiploidy in childhood acute lymphoblastic leukemia with gain of a single chromosome 21.

Department of Oncology, University Children’s Hospital, Zurich, Switzerland, Department of Oncology and Hematology, Children’s Hospital, St. Gallen, Switzerland, Department of Oncology, Children’s Hospital, Luzern, Switzerland, Department of Oncology, Children’s Hospital, Locarno, Switzerland, Department of Oncology and Hematology, University Children’s Hospital, Basel, Switzerland, Department of Hematology and Oncology, Children’s Hospital Aarau Switzerland, and National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Dublin, Ireland