Abstract 4841: NF-kB - p53 gene associations and prostate cancer risk

Abstract

Abstract Introduction: Prostate cancer is the most commonly diagnosed male malignancy and the second leading cause of cancer death, representing 29% of all male cancer deaths. Various tumor suppressor genes have been identified, playing a role in prostate cancer development and progression. The tumor suppressor gene p53, is the most commonly mutated gene in human cancers. Studies show that p53 can induce activation of NF-kB, and loss of NF-kB activity specifically abrogated the p53-mediated apoptotic response, without impinging on the ability to activate expression of target genes or induce cell-cycle arrest. NF-kB plays a well-known function in the regulation of immune responses and inflammation, but growing evidences support a major role in oncogenesis. Although it has been suggested that activation of NF-kB is not directly associated with tumor development and progression, NF-kB has been considered to be a major biomarker and therapeutic target. Enhanced NF-κB activity can be directly induced by mutations of NF-κB genes and/or oncogenes that activate the NF-κB signaling pathway. In view of the earlier reports, this study is aimed at investigating the role of p53 and NF-kB gene polymorphisms in prostate cancer risk and the possible correlation between p53-NF-kB gene in development and progression of disease. Materials & methods: Blood samples were collected from 113 prostate cancer patients and a 135 normal healthy and age matched male subjects from local wellness clinics. DNA extracted from the blood at the Genetic Research Institute of the Desert is used to screen two gene polymorphisms in p53 and NF-kB using PCR-RFLP,gel electrophoresis and PCR and ABI 3130 CE-based genetic analysis. Genotype data was recorded from two methods and analyzed for frequency, Chi-Square & correlations coefficients using SPSS statistical package (PASW Grad pack 18). Results: Our data showed a strong association of p53 codon248 (p<0.001) and NF-kB gene polymorphism (p<0.031) with prostate cancer. Further analysis of these two gene combinations in prostate cancer and controls showed a significant correlation (p<0.001) between the two gene polymorphisms in prostate cancer patients. Individually, both p53codon 248 and NF-kB del were robustly associated with prostate cancer occurrence. Moreover, the gene-gene combination predicted the occurrence of prostate cancer. Conclusions: A strong association of p53 and NF-kB gene polymorphisms with prostate cancer suggests these two genes to be possible markers for prostate cancer risk. NF-kB is known to crosstalk with many other tumor-related signaling pathways including p53. Given the unprecedented role of p53-NF-kB in tumorigenesis, p53-NF-kB risk alleles can be used as a screening device for cancer susceptibility to inform the need for more intensive ongoing cancer surveillance. Citation Format: Radhika Gade Andavolu, Catherine Stafford, Murthy Vs Andavolu, Jean-Luc Cardenas, Jacob Rubin, Ross Shore, Svetlana Rubakovic. NF-kB - p53 gene associations and prostate cancer risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4841. doi:10.1158/1538-7445.AM2015-4841