title: Role of the MDM2 promoter polymorphism (-309T>G) in acute myeloid leukemia development.
abstract: BACKGROUND
  The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML.
  
  
  METHODS
  A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy.
  
  
  RESULTS
  MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p=0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036).
  
  
  CONCLUSIONS
  The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.
authors: Department of Genetics, Osmania University, Hyderabad, India E-mail : sattivishnupriya@gmail.com.
authors: Anuradha
authors: A
authors: Cingeetham
authors: Sugunakar
authors: S
authors: Vuree
authors: Sangeeta
authors: S
authors: Jiwatani
authors: Sailaja
authors: S
authors: Kagita
authors: Nageswara Rao
authors: NR
authors: Dunna
authors: Phanni Bhushann
authors: PB
authors: Meka
authors: Manjula
authors: M
authors: Gorre
authors: Sandhya
authors: S
authors: Annamaneni
authors: Raghunadharao
authors: R
authors: Digumarti
authors: Sudha
authors: S
authors: Sinha
authors: Vishnupriya
authors: V
authors: Satti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2