RESUMO
Survivin, a member of the inhibitor of apoptosis (IAP) protein family that inhibits caspases and blocks cell death, is highly expressed in most cancers and is associated with a poor clinical outcome. Survivin has consistently been identified by molecular profiling analysis to be associated with high tumour grade cancers, different disease survival and recurrence. Polymorphisms in the survivin gene are emerging as powerful tools to study the biology of the disease and have the potential to be used in disease prognosis and diagnosis. The survivin gene polymorphisms have also been reported to influence tumour aggressiveness as well as survival of cancer patients. The differential expression of survivin in cancer cells compared to normal tissues and its role as a nodal protein in a number of cellular pathways make it a high target for different therapeutics. This review discusses the complex circuitry of survivin in human cancers and gene variants of survivin, and highlights novel therapy that targets this important protein.
RESUMO
BACKGROUND AND AIM: p73, a novel P53 homolog and plays an important role in modulating cell cycle control, apoptosis and cell growth while P21, functions to negatively control the cell cycle. P53 up regulates p21 expression in response to deoxyribonucleic acid damage leading to cell cycle arrest at G1 checkpoint. In the present study, we are targeting p21 codon 31 and p73 gene variants of G4C14‑to‑A4T14 (Exon 2) polymorphism for bladder cancer (BC) risk in North Indians. MATERIALS AND METHODS: The above gene variants of P21 and P73 were assessed in the case‑control study comprising of 200 BC cases and 200 healthy controls of the same age, gender and similar ethnicity. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method and PCR‑based confronting two‑pair primers (PCR with CTPP). RESULTS: The variant genotype of p73Exon 2 polymorphism showed significant risk for BC (p = 0.014). While combining with heterozygous genotype, variant genotype of p73Exon2 showed a significant association with BC risk (p = 0.010). While in case of p21 codon31 showed no significant association for BC risk at genotypic level. Significant association between p73Exon2 polymorphism and smoking was observed for BC risk. Furthermore, gene combination analysis revealed that AT/AT‑Ser/Ser is associated with risk for BC. Variant genotype of P73Exon2 was associated with reduced risk of recurrence (p = 0.039) in superficial BC patients receiving Bacillus Calmette‑Guerin treatment thus showing least survival (log rank = 0.029). CONCLUSION: Our study provided evidence that the p73 G4C14 > A4T14 (Exon2) polymorphisms were associated with higher risk of BC in North Indian population.