title: Interaction Between IGF1 Polymorphisms  and the Risk of Acute Lymphoblastic  Leukemia in Chinese Children.
abstract: OBJECTIVE
  IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays.
  
  
  RESULTS
  We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1.
  
  
  CONCLUSIONS
  Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level.
authors.forename: Lingling
authors.initials: L
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Lulu
authors.initials: L
authors.lastname: He
authors.forename: Yao
authors.initials: Y
authors.lastname: Xue
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Liucheng
authors.initials: L
authors.lastname: Rong
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Fang
authors.forename: Hongjun
authors.initials: H
authors.lastname: Miao
mesh_terms: D020413:3' Untranslated Regions; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors; D015533:Transcriptional Activation
chemical_list: D020413:3' Untranslated Regions; C583557:IGF1 protein, human; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I