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Gene-gene interactions in the folate metabolic pathway influence the risk for acute lymphoblastic leukemia in
Bohanec Grabar Petra1, Jazbec Janez, Dolzan Vita
1Institute of Biochemistry, University of Ljubljana, Ljubljana, Slovenia.
Insights
Genetic variations in folate metabolism may influence childhood acute lymphoblastic leukemia (ALL) risk. Certain gene combinations, particularly those reducing methylation capacity, appear to offer protection against developing ALL.
Area of Science:
- Genetics
- Oncology
- Biochemistry
Background:
- Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer.
- Genetic polymorphisms in the folate pathway are implicated in DNA synthesis and methylation, potentially affecting cancer risk.
- Understanding these genetic factors is crucial for identifying susceptibility to childhood ALL.
Purpose of the Study:
- To investigate the influence of common genetic polymorphisms in the folate metabolic pathway on the risk of childhood ALL.
- To analyze specific gene variants in MTHFR, TS, MS, and MTRR in children with ALL and healthy controls.
- To explore potential gene-gene interactions affecting ALL susceptibility.
Main Methods:
- Case-control study involving 68 children with ALL and 258 healthy controls.
- Genotyping analysis of common polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), methionine synthase (MS), and methionine synthase reductase (MTRR).
- Statistical analysis to compare genotype frequencies and calculate odds ratios (OR) and confidence intervals (CI).
Main Results:
- No significant differences in the frequencies of individual polymorphisms were found between ALL patients and controls.
- Combined MTHFR 677CT/TT and MS 2756AG/GG genotypes showed a non-significant trend towards reduced ALL risk (OR 2.24).
- A significant reduction in ALL risk was observed with combined MTHFR 677CT/TT, MS 2756AG/GG, and MTRR 66AG/GG genotypes (OR 0.312, P=0.032).
Conclusions:
- Individual folate pathway polymorphisms do not appear to significantly alter the risk for childhood ALL.
- Gene-gene interactions within the folate pathway, specifically those decreasing methylation capacity, may have a protective effect against childhood ALL.
- Further research into gene-gene interactions is warranted to understand their role in ALL pathogenesis.
Abstract:
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Genetic polymorphisms in the folate metabolic pathway may contribute to the susceptibility to childhood ALL because they affect the DNA synthesis, methylation and repair. We analysed common genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), methionine synthase (MS) and methionine synthase reductase (MTRR) in 68 children with ALL and 258 healthy controls to investigate their influence on the risk for ALL. No significant differences in frequencies of separate polymorphisms were observed between both groups. Combined MTHFR 677CT/TT and MS 2756AG/GG genotypes showed a nonsignificant tendency to reduce the risk for ALL 2.24-fold (CI: 0.191 - 1.037, P: 0.061). The risk was significantly reduced in carriers of combined MTHFR 677CT/TT, MS 2756AG/GG and MTRR 66AG/GG genotypes (OR: 0.312; CI: 0.107 - 0.907; P: 0.032). Our results suggest that gene - gene interactions that may decrease the methylation capacity might have a protective effect on the risk for childhood ALL.
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