Relationships between perinatal and maternal characteristics and hepatoblastoma: a report from the UKCCS

Within the context of a national population-based case-control study – the United Kingdom Childhood Cancer Study (UKCCS) – we aimed to explore relationships between perinatal and maternal factors and childhood hepatic tumours, for participants with data available from medical records. 26/28 children with hepatic tumours (22/24 hepatoblastomas, 4/4 hepatocellular carcinomas (HCC)) and 4753 age- and sex-matched controls were included. Polyhydramnios was associated with 0.9% of control pregnancies and 13.6% of case pregnancies (Odds Ratio (OR)=28.64, 95% Confidence Interval (CI)=6.94–118.21, P<0.0001); eclampsia or severe pre-eclampsia complicated the pregnancies of 16.7% of mothers whose children developed hepatoblastoma compared with 0.5% of control pregnancies (OR=52.50, 95% CI=10.75–257.05, P<0.0001). Three children with hepatoblastoma weighed <1500 g at birth, two of whom weighed <1000 g (OR for birthweight <1500 g=69.00, 95% CI=11.98–397.17, P<0.0001). Of children with hepatoblastoma, 50% (11/22) had records of congenital anomalies, as did two of their mothers. Three mothers of children with hepatoblastoma had diagnoses of cancer – two of papillary carcinoma of the thyroid and one of acute lymphoblastic leukaemia (ALL). Paediatricians and others should be alert to the possibility of familial or genetic syndromes in children with hepatoblastomas. Potential links between maternal pre-eclampsia, low birthweight and subsequent malignancy merit further investigation. Hepatoblastoma is an extremely rare childhood tumour, but understanding the mechanism(s) underlying severe pre-eclampsia and eclampsia may also shed light on factors that contribute to the development of hepatoblastoma

The putative role of transforming viruses in childhood acute lymphoblastic leukemia

The putative role of transforming viruses in childhood acute lymphoblastic leukemia Epidemiological evidence suggests that infection is involved in the etiology of common acute lymphoblastic leukemia, either by stimulating an inappropriate immune response or in the form of a classical transforming agent. In an attempt to elucidate the role that infection is playing in this disease, we used representational difference analysis (RDA) to examine tumor samples for the presence of exogenous genomes. Twenty RDA experiments were carried out, using four different restriction enzymes, but no exogenous sequences were identified within leukemic cells. These results suggest that it is unlikely that a single, direct transforming agent is involved in the pathogenesis of common acute lymphoblastic leukemia

Germline mutation rate in the hypervariable minisatellite CEB1 in the parents of children with leukaemia

Gardner and colleagues advanced the hypothesis that the Seascale leukaemia cluster may have been caused by germ cell mutagenesis due parental preconceptional irradiation (PPI) of fathers working at the Sellafield nuclear installation. Recent evidence has shown that PPI can lead to an increased germline mutation rate in certain minisatellite loci, allowing previously undetectable levels of germline sensitivity to IR to be measured. In this study, we have investigated the hypothesis that childhood leukaemia may be associated with parental germ cell sensitivity detected by an increased parental germline minisatellite mutation rate. To test this we compared the germline mutation rate of the hypervariable minisatellite locus, CEB1 in family trios (both parents and their child) of children with leukaemia (n = 109) compared with normal families (n = 64). We found no significant difference in mean mutation rate of parents of children with leukaemia and control children (0.0414 vs 0.0887; P > 0.05). The majority of germline mutations (95%) were paternal, and unaffected by the presence of leukaemia cells in the sample. We found no significant differences in mean minisatellite allele size (72 vs 68 repeats; p > 0.05), or mutational spectrum (gains or losses of repeats) in the parents of case and control children. Although preliminary, our results suggest that childhood leukaemia is unlikely to be associated with increased germline minisatellite instability resulting from exposure of parental germ cells to mutagens such as IR