Journal of B.U.ON. : official journal of the Balkan Union of Oncology · 2016
MDM2 344T>A polymorphism; could it be a predictive marker of anthracycline resistance?
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Arfaoui Abir, Douik Hayet, Kablouti Ghalia, Chaaben Arijben, Handiri Nadia, Zid Zaineb, Ouni Nesrine, Zouiouch Farah, Ayari Fayza, Mamoghli Tensime, Bouassida Jihen, Harzallah Latifa, Guemira Fethi
Аннотация
PURPOSE: 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.
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.