title: The association of DNA methyltransferase 1 gene polymorphisms with susceptibility to childhood acute lymphoblastic leukemia.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, China; Nanjing Red Cross Blood Center, 210003 Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, 210009 Nanjing, China.
authors.forename: Luting
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Laboratory medicine, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, China.
authors.forename: Feixia
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Nanjing Red Cross Blood Center, 210003 Nanjing, China.
authors.forename: Xubing
authors.initials: X
authors.lastname: Cai
authors.affiliation: Nanjing Red Cross Blood Center, 210003 Nanjing, China.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, China. Electronic address: sypan@njmu.edu.cn.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, 210009 Nanjing, China. Electronic address: chenluo@cpu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Luo
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C411744:DMAP1 protein, human; D012097:Repressor Proteins
keywords: Acute lymphoblastic leukemia; DNA methyltransferase 1; Polymorphism; Susceptibility