Survivin Gene Polymorphisms Research Articles

The survivin -31 snp in human colorectal cancer correlates with survivin splice variant expression and improved overall survival

Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386 C/T and -31 G/C polymorphisms were investigated. Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR. Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the -31 G/C snp may be related to CRC development and improved overall survival. Our results support a role of survivin in colorectal carcinogenesis while the -31 G/C snp may constitute a marker of survival.

Prognostic Significance of Survivin Polymorphisms on Non-small Cell Lung Cancer Survival

Survivin is an apoptotic inhibitor, involves in regulation of apoptosis and cell cycle progression, and its polymorphisms may influence the development and progression of cancer. This study evaluated the impact of the survivin gene polymorphisms on survival of non-small cell lung cancer (NSCLC) patients. In this case-cohort follow-up study, a total of 568 NSCLC patients were investigated and 12 single nucleotide polymorphisms in survivin gene were genotyped by using the Illumina GoldenGate platform. During the maximum of 72 months of follow-up, 314 (55.11%) deaths were observed. After adjusting for age, gender, smoking status, histology, stage, surgical operation, and chemotherapy or radiotherapy status, Cox hazard proportional model suggested that four single nucleotide polymorphisms had statistically significant impacts on NSCLC survival (rs3764383, AG/GG versus AA, hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.62-0.99; rs8073069, GG versus CG/CC, HR = 1.76, 95% CI: 1.16-2.67; rs4789551, GG versus AG/AA, HR = 2.04, 95% CI: 1.08-3.86; rs1042489, GG versus AG/AA, HR = 1.37, 95% CI: 1.03-1.83). Further combined analysis showed that the high risk group (3-4 unfavorable loci) presented a 1.84-fold (95% CI: 1.22-2.77) increased risk compared with low risk group (0-2 unfavorable loci). Among 185 stage III to IV patients who received only chemotherapy, only the potentially functional rs8073069 still had a significantly increased risk on the prognosis of NSCLC (GG versus CG/CC, HR = 2.06, 95% CI: 1.10-3.87). Our results suggest that polymorphisms in survivin may be a genetic modifier for NSCLC prognosis in this Chinese population.

Effects of Caspase-9 and Survivin Gene Polymorphisms in Pancreatic Cancer Risk and Tumor Characteristics

This case-control study was performed to evaluate the association between a specific caspase-9 polymorphism as well as the genetic polymorphism -31G/C located in the cycle-dependent elements/cell cycle homology regions repressor element of the human survivin promoter and the risk of pancreatic cancer. Eighty patients with pancreatic cancer and 160 healthy controls were investigated for genotype and allelic frequencies of caspase-9 1263A/G and survivin -31G/C polymorphisms by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. The G carrier group of patients and the G allele of caspase-9 1263A/G were overrepresented among the pancreatic cancer cases. With regard to tumor characteristics, a statistically significant association was detected between the survivin C carrier group of patients and the advanced T stage as well as the presence of lymph node metastasis. The caspase-9 G allele confers increased susceptibility to pancreatic cancer development, and the survivin C carriage status may be related to aggressive features of this malignancy.

The Survivin −31 Snp in Human Colorectal Cancer Correlates with Survivin Splice Variant Expression and Improved Overall Survival

Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and −31G/C polymorphisms were investigated.Methods: Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR.Results: Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the −31G/C snp may be related to CRC development and improved overall survival.Conclusion: Our results support a role of survivin in colorectal carcinogenesis while the −31G/C snp may constitute a marker of survival.