1. ¹Cancer Immunogenetics Laboratory, Division of Human Development, University of Manchester, Manchester, UK
2. ²ALSPAC DNA and Cell Line Bank, University of Bristol, Bristol, UK
3. ³CRUK Paediatric and Familial Cancer Study Group, University of Manchester, Manchester, UK
4. ⁴Academic Unit of Paediatric Oncology, Division of Human Development, University of Manchester, Manchester, UK
5. ⁵Department of Genetics, University of Leicester, Leicester, UK

Correspondence: Dr GM Taylor, E-mail: gmtaylor@manchester.ac.uk

Received 2 November 2006; Revised 28 February 2007; Accepted 28 February 2007; Published online 27 March 2007.

Abstract

Gardner and co-workers advanced the hypothesis that the Seascale leukaemia cluster could have been caused by new mutations in germ cells, induced by paternal preconceptional irradiation (PPI) exposure at the Sellafield nuclear installation. Since evidence has shown that PPI can increase the de novo germline mutation rate in hypervariable minisatellite loci, we investigated the hypothesis that sporadic childhood leukaemia might be associated with an increased parental germline minisatellite mutation rate. To test this hypothesis, we compared de novo germline mutation rates in the hypervariable minisatellite locus, CEB1, in family trios (both parents and their child) of children with leukaemia (n=135) compared with unaffected control families (n=124). The majority of case and control germline mutations were paternal (94%); the mean paternal germline mutation rates of children with leukaemia (0.083) and control children (0.156) were not significantly different (odds ratio, 95% confidence interval: 0.50, 0.23–1.08; P=0.11). There were no significant differences in case and control parental allele sizes, case and control germline mutation progenitor allele sizes (2.74 vs 2.54 kb; P=0.56), case and control mutant allele sizes (2.71 vs 2.67 kb; P=0.90), mutant allele size changes (0.13 vs 0.26 kb; P=0.10), or mutational spectra. Within the limitation of the number of families available for study, we conclude that childhood leukaemia is unlikely to be associated with increased germline minisatellite instability.