P-33: Association between Survivin Gene Promoter -31G/C Polymorphism and Breast Cancer Risk in East Azerbayjan
Objective: Breast cancer has been the most common malignancy in women and an important cause of cancer death worldwide. Survivin as an apoptosis inhibitor plays an important role in the development and progression of breast cancer.Polymorphisms in the survivin gene promoter may influence survivin production or activity. A common polymorphism at this region (-31G/C) has been extensively studied and reported to influence survivin expression in various cancers. The C-31G polymorphism in the survivin promoter could de-repress the cell cycle- dependent transcription of survivin gene, resulting in over expression of survivin. In this hospital- based, case- control study, we investigated the correlation of the genetic polymorphism of -31G/C located in the cycle- dependent elements/cell cycle homology regions repressor element of the human survivin promoter to the occurrence of breast cancer in an Iranian population. Materials and Methods: The -31G/C single nucleotide polymorphism(SNP) of survivin promoter in peripheral blood samples from 94 breast cancer patients with pathologically confirmed BC and 82 healthy subjects was analyzed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and gene sequencing.The samples were recruited at Imam Reza and Nour Nejat hospital from 2008 to 2010. Results: The genotype frequencies for -31G/G, -31G/C and -31C/C were 50 %, 46.8 % and 3.2 % respectively in breast cancer patients, and 50 %, 45.1 % and 4.9 % in healthy individuals. Also the frequencies for -31C allele were 26 % and 27 % in cases and controls respectively.No statistically significant association was found between breast cancer risk and the variant genotypes(CC and CG). Conclusion: Survivin is expressed in G2/M phase of the cell cycle and it is largely controlled at the transcription level.The transcription of survivin is mediated by CDE (GGCGG) and CHR (ATTTGAA) repressor elements located in the proximal region of the survivin promoter.-31G/C polymorphism is likely associated with de-repression of survivin transcription in the G1 phase in various cancers.Many studies have shown that this SNP may be a functional SNP within the promoter.In contrary to our expectation, we could not find any significant differences in the genotype distributions of the -31G/C variants among two compared groups.Because SNPs often are different between ethnic populations, additional studies with larger sample sizes are needed to verify the association of survivin promoter polymorphism with BC.