TP53 and P21 polymorphisms: Response to cisplatinum/paclitaxel-based chemotherapy in ovarian cancer

• Published in: Biochemical and biophysical research communications 2006-02, Vol.340 (1), p.256-262
• Main Authors: Santos, Alexandra M., Sousa, Hugo, Portela, Catarina, Pereira, Deolinda, Pinto, Daniela, Catarino, Raquel, Rodrigues, Carla, Araújo, Ana P., Lopes, Carlos, Medeiros, Rui
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biomarkers, Tumor - genetics; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cyclin-Dependent Kinase Inhibitor p21 - genetics; DNA Mutational Analysis - methods; Female; Genetic Predisposition to Disease - epidemiology; Genetic Testing - methods; Humans; Incidence; Middle Aged; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; P21 3′UTR polymorphism; Paclitaxel; Paclitaxel - administration & dosage; Pharmacogenomics; Polymorphism, Genetic; Portugal - epidemiology; Prognosis; Risk Assessment - methods; Risk Factors; Survival Analysis; Survival Rate; TP53 codon 72 polymorphism; Treatment Outcome; Tumor Suppressor Protein p53 - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.11.176

Ovarian cancer (OC) is the most lethal gynaecologic cancer and its standard treatment consists of platinum-based chemotherapy after cytoreductive surgery. The p53 protein plays a critical role on different cellular processes in response to DNA damage and it is responsible for transcriptional induction of the P21 gene. We have analysed 114 blood samples in order to investigate the effect of the TP53 codon 72 and the P21 3′UTR polymorphisms in response to cisplatinum/paclitaxel chemotherapy for OC treatment. The genotypes of the TP53 codon 72 and P21 3′UTR polymorphism were identified using AS-PCR and PCR-RFLP, respectively. Our results indicate that the TP53 P allele is associated with a worse prognosis ( P = 0.011) while P21 polymorphism genotypes did not reveal any statistically significant result ( P > 0.05). Furthermore, simultaneous carriers of the TP53 AA genotype and the P21 CC genotype demonstrate a longer progression-free interval ( P = 0.020). This study suggests that the characterisation of a genetic profile can contribute to the definition of a better chemotherapy treatment.