title: MDM2 344T>A polymorphism; could it be a predictive marker of anthracycline resistance?
abstract: OBJECTIVE
  To find a possible association between the Mouse Double Minute 2(MDM2) 344T>A, alone and in combination with p53 72 Arg/Pro polymorphism, and resistance to anthracycline-based chemotherapy of breast cancer in Tunisia.
  
  
  METHODS
  This study enrolled 542 patients with invasive ductal carcinoma (IDC) treated with anthracycline-based chemotherapy. Genomic DNA was isolated from whole blood, using the phenol chloroform method. Anthracycline response was scored according to the World Health Organization (WHO). MDM2 344T>A polymorphism was genotyped using real time polymerase chain reaction (RT-PCR) with the TaqMan method. Data was statistically analyzed using the x2 test.
  
  
  RESULTS
  Response was evaluated in 400 patients, of whom a quarter was found to be resistant to chemotherapy. Genetic data revealed that resistance to anthracycline-based chemotherapy did not seem to be correlated with 344T>A polymorphism in the studied population. Also, no significant association was found between the single nucleotide polymorphism (SNP) 344T>A status and clinicopathologic parameters (p>0.05 for all comparisons). Moreover, analysis of p53 rs1042522 and MDM2 rs1196333 combination showed no significant association between these two genetic variants and anthracycline resistance (p=0.2).
  
  
  CONCLUSIONS
  Our findings provide no evidence indicating that SNP 344 T>A may affect response to anthracycline-based chemotherapy. However, the results obtained from the combination of SNPs 344T>A of MDM2 and 72 Arg/Pro of p53, do not support the hypothesis of the prominent role of common p53 and MDM2 variations in the genetic mechanisms of chemotherapy resistance in breast cancer.
authors: Salah Azaiz Institute, Tunis, Tunisia.
authors: Abir
authors: A
authors: Arfaoui
authors: Hayet
authors: H
authors: Douik
authors: Ghalia
authors: G
authors: Kablouti
authors: Arijben
authors: A
authors: Chaaben
authors: Nadia
authors: N
authors: Handiri
authors: Zaineb
authors: Z
authors: Zid
authors: Nesrine
authors: N
authors: Ouni
authors: Farah
authors: F
authors: Zouiouch
authors: Fayza
authors: F
authors: Ayari
authors: Tensime
authors: T
authors: Mamoghli
authors: Jihen
authors: J
authors: Bouassida
authors: Latifa
authors: L
authors: Harzallah
authors: Fethi
authors: F
authors: Guemira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D016158:Genes, p53; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
chemical_list: D018943:Anthracyclines; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2