A case–control study of childhood acute lymphoblastic leukaemia and polymorphisms in the TGF‐β and receptor genes

Background Inherited genetic variants in critical genes can putatively modulate susceptibility to childhood acute lymphoblastic leukemia (ALL). Methods We used allelic discrimination method to genotype 19 polymorphisms in the transforming growth factor‐β1 ( TGF‐β1 ) , transforming growth factor‐β receptor 1 ( TGF‐βR1 ) and transforming growth factor‐β receptor 2 ( TGF‐βR2 ) genes in 460 cases of childhood acute ALL and 552 ethnically matched controls. The genotyped polymorphisms included functional and tagging variants to cover the three genes in entirety. We used multidimensionality reduction (MDR) method to test effect of multiple genes on disease susceptibility. In order to increase statistical power and detect susceptibility variants not directly genotyped in this study, we used imputation using HapMap data. Results None of the genotyped polymorphisms or the consequent haplotypes showed any association with risk modulation. The results, however, did show a marginal association (odds ratio OR 0.76, 95% confidence interval CI 0.59–0.97) of the variant allele for the rs10417924 polymorphism located at 3′untranslated region of the TGF‐β1 gene with the B‐cell lineage ALL. No other polymorphism showed any association with childhood ALL susceptibility. A signal of marginal significance for the rs10417924 polymorphism in the TGF‐β1 gene in B‐cell lineage ALL showed up with both MDR and imputation techniques. Conclusion These data rule out the role of polymorphisms in the TGF‐β1, TGF‐βR1 and TGF‐βR2 genes in susceptibility to childhood ALL. However, for B‐lineage ALL, the role of the rs10417924 polymorphism in TGF‐β1 gene needs further investigation. Pediatr Blood Cancer 2009;52:819–823. © 2009 Wiley‐Liss, Inc.