Polymorphisms and haplotypes of the NBS1 gene in childhood acute leukaemia.

DNA repair gene polymorphisms and mutations may influence cancer risk. The product of the NBS1 gene, nibrin, is functionally involved in the double-strand DNA break repair system. Heterozygous, germline mutations of the NBS1 gene are associated with an increased risk of tumours. Thus, common polymorphism and haplotypes of NBS1 may contribute to the risk of cancer. This study verified whether polymorphisms of the NBS1 gene may influence susceptibility to the development of childhood acute leukaemia. We genotyped six polymorphisms of the NBS1 gene in 157 children with acute leukaemia and 275 controls. The TT genotype of c.2071-30A>T polymorphism was higher in leukaemia patients than in controls. Genotyping data from the six polymorphic loci in NBS1 in leukaemia patients and controls were used to impute haplotypes. Two of the evaluated haplotypes were associated with significantly increased leukaemia risk (P=0.0038 and P<0.0001). Our results suggest that some specific haplotypes of the NBS1 gene may be associated with childhood leukaemia.