A case-control study of childhood acute lymphoblastic leukaemia and polymorphisms in the TGF-beta 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-beta1 (TGF-beta1), transforming growth factor-beta receptor 1 (TGF-betaR1) and transforming growth factor-beta receptor 2 (TGF-betaR2) 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-beta1 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-beta1 gene in B-cell lineage ALL showed up with both MDR and imputation techniques.


CONCLUSIONS
These data rule out the role of polymorphisms in the TGF-beta1, TGF-betaR1 and TGF-betaR2 genes in susceptibility to childhood ALL. However, for B-lineage ALL, the role of the rs10417924 polymorphism in TGF-beta1 gene needs further investigation.
Dai
Liping
L
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Gast
Andreas
A
Horska
Alexandra
A
Schrappe
Martin
M
Bartram
Claus R
CR
Hemminki
Kari
K
Kumar
Rajiv
R
Bermejo
Justo Lorenzo
JL
D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II