In a previous study, we obtained preliminary evidence in a small series of patients (n = 63) suggesting that susceptibility to childhood common acute lymphoblastic leukaemia (c-ALL) was associated with an allele at the HLA-DPB1 locus, DPB1*0201. We have now tested this hypothesis by comparing the frequency of children with leukaemia (n = 982) who typed for specific DPB1 alleles and two groups of non-leukaemic children, one consisting of children with solid tumours, excluding lymphomas (n = 409), the other consisting of normal infants (n = 864). We found that significantly more children with c-ALL and T-ALL, but not pro-B ALL or acute non-ALL typed for DPB1*0201 as compared with children with solid tumours [odds ratio (OR), 95% confidence interval (CI) for c-ALL: 1.76, 1.20-2.56; T-ALL: 1.93, 1.01-3.80] and normal infants (OR, 95% CI for c-ALL: 1.83, 1.34-2.48; T-ALL: 2.00, 1.10-3.82). In childhood c-ALL, significantly more children than those with solid tumours or normal infants typed for DPB1 alleles coding specific polymorphic amino acids lining the antigen-binding site of the DPbeta1*0201 allotypic protein, suggesting that susceptibility to childhood c-ALL may be influenced by DPbeta ABS amino acid polymorphisms shared by DPbeta1*0201 and other DPbeta1 allotypes. These results point to a mechanism of c-ALL susceptibility that involves the presentation of specific antigenic peptides, possibly derived from infectious agents, by DPbeta1*0201-related allotypic proteins, leading to the activation of helper T cells mediating proliferative stress on preleukaemic cells.

SummaryThe relationship between childhood cancer and having been breastfed in infancy was investigated in the UK Childhood Cancer Study (UKCCS), a national, population-based case-control study. Analyses included 3500 children with cancer (cases) of whom 1637 were diagnosed with leukaemia, 114 with Hodgkin's disease, 228 with non-Hodgkin's lymphoma and 1521 with other cancer and 6964 controls. 62% cases and 64% controls were reported to have ever been breastfed. There was weak evidence, of borderline statistical significance, that having been breastfed was associated with a small reduction in the odds ratios for leukaemia (odds ratio = 0.89, 95% Cl 0.80-1.00, P = 0.06), and for all cancers combined (odds ratio = 0.92, 95% Cl 0.84-1.00, P = 0.05). Combining data from the UKCCS with results from other published studies showed a small reduction in the odds ratios for leukaemia, Hodgkin's disease, non-haematological cancers, and all childhood cancers combined, associated with ever having been breastfed. It is unclear whether the apparent small reduction in the odds ratio for these various types of childhood cancer is a generalized effect of breastfeeding or whether it reflects some systematic bias in the majority of studies that have investigated the question.