The association of DNA methyltransferase 1 gene polymorphisms with susceptibility to childhood acute lymphoblastic leukemia.

BACKGROUND

It has been suggested that aberrant DNA methylation is a common epigenetic alteration in malignancies. Genetic variations in DNA methyltransferase 1 gene (DNMT1), which encodes the maintenance methyltransferase, have been demonstrated to be involved in cancer susceptibility. In the present study, we investigated whether genetic polymorphisms in DNMT1 could be associated with risk of childhood acute lymphoblastic leukemia (ALL) in a Chinese population.

METHODS

We selected seven tagging single-nucleotide polymorphisms (tagSNPs, rs11880388, rs10423341, rs7253062, rs11085721, rs2228611, rs2228612 and rs16999593) in DNMT1 and genotyped these SNPs by using TaqMan method in a case-control study of 377 patients with ALL and 500 healthy controls. The logistic regression was used to assess the genetic associations with occurrence of ALL with adjustment for possible confounders.

RESULTS

We found that one (rs11085721) of the seven tagSNPs was significantly associated with the risk of ALL. Compared with individuals' with DNMT1 rs11085721 GG genotype, those subjects carrying the rs11085721 GT genotypes were associated with significantly increased risk for ALL (GT vs. GG:OR=1.29, 95% CI=1.10-1.51). Similar association was also observed when combined the individuals with rs11085721 GT and rs11085721 TT genotypes (GT/TT vs. TT:OR=1.29, 95% CI=1.10-1.50). No positive results were observed for the other tagSNPs.

CONCLUSIONS

Our results suggest that the DNMT1 rs11085721 polymorphism may confer susceptibility to ALL in the Chinese population. The initial findings should be validated by large population-based prospective studies in the future.