Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population.
BACKGROUND
Childhood acute lymphoblastic leukaemia (ALL) is a complex disease caused by a combination of genetic susceptibility and environmental exposure. Previous genome-wide association studies have reported several single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. Several variations in genes encoding enzymes involved in carcinogenesis are suggested as being associated with an increased risk of ALL development.


METHODS
We enrolled 77 paediatric ALL patients and 122 healthy controls, and in addition parental DNA was also available for 45 probands. SNPs rs10821936 (ARID5B), rs4132601 (IKZF1), rs2239633 (CEBPE), rs3731217 (CDKN2A) and rs1800566 (NQO1) and the presence of GSTT1 and GSTM1 null variants were detected. For statistical analysis the hybrid method of two designs 'Haplin' was used as well as linkage disequilibrium for family-based association studies.


RESULTS
We identified the SNP rs10821936 in the ARID5B gene as being statistically significantly associated with childhood ALL, especially if the C allele is in a homozygous state, relative risk (RR) 4.65, 95% CI: 2.03-10.6, p = 0.0006. Statistically significant differences were not found in other SNPs. We found risk combinations including all five variations, the strongest association being found in a combination where all five genetic variants are in a homozygous state, CCTTTTTTCC, p = 0.032.


CONCLUSIONS
The identified SNP rs10821936 could serve as a potential risk marker for childhood ALL development. Further studies in an independent population are needed for verification.
Scientific Laboratory of Molecular Genetics, Riga Stradiņš University, Riga, Latvia; Institute of Oncology, Riga Stradiņš University, Riga, Latvia.
Madara
M
Kreile
Scientific Laboratory of Molecular Genetics, Riga Stradiņš University, Riga, Latvia.
Linda
L
Piekuse
Scientific Laboratory of Molecular Genetics, Riga Stradiņš University, Riga, Latvia.
Dmitrijs
D
Rots
Scientific Laboratory of Molecular Genetics, Riga Stradiņš University, Riga, Latvia.
Zane
Z
Dobele
Department of Hematology and Oncology, Children's Clinical University Hospital, Riga, Latvia.
Zhanna
Z
Kovalova
Latvian Biomedical Research and Study Centre, Riga, Latvia.
Baiba
B
Lace
ARID5B; IKZF1; childhood acute lymphoblastic leukaemia; single nucleotide polymorphisms