Biochemical study of survivin -31G/C promoter polymorphism in breast Cancer

Abstract

Breast cancer is the most common cancer and also the leading cause of cancer mortality in women worldwide. Survivin is a member of the inhibitor of apoptosis (IAP) family, which has been identified recently. Unlike other IAP proteins, survivin is generally not found in normal adult tissues but notably expressed in the most common human cancers including stomach, colorectal, lung and breast. In cancer cells, overexpression of survivin at both protein and mRNA levels is linked to genetic variant-31G/C in the survivin promoter. P53-Abs were discovered 20 years ago during the course of tumor-associated antigens screening. The discovery of p53 mutation and accumulation of p53 in human tumors shed new light on the p53 humoral response. The aim of work: investigate-31 G/C single nucleotide polymorphism (SNP)of survivin promoter in breast cancer patients .Measurement of the level of p53 antibodies in them and detecting the association between it and the polymorphism also. Patients and methods: 100 subjects were enrolled in in this study. All were women in the age between 40 and 65 (60 breast cancer cases and 40 control divided into two groups according to age: Group 1 ≤ 50 years (27.3 ± 4.87) and Group 2 > 50(24.83 ± 6.12). Results: Our study shows a significant difference in the prevalence of the survivin promoter polymorphism (-31G > C) between the case and control groups, P value (P = 0.005*). Notably, the combined prevalence of the GC and CC genotypes (GC + CC), reflecting the prevalence of the C allele, was significantly greater in the breast cancer group than in the control group (P= 0.002*) with rates of 29% and 6%, respectively. These results imply that the C allele at position-31 in the promoter region of the survivin gene increases an individual's susceptibility to breast cancer. Also, the risk of developing cancer was 4.05 times higher in patients with the GC or CC genotype (GC + CC) than in patients with the GG genotype, and this difference was statistically significant (95% CI: (1.48-11.09). Besides, in the breast cancer group, the GG genotype was present in 35 patients, whereas the GC + CC genotype was present in 25 patients. As regard the level of p53 antibodies, there was a significant difference (p=0.025) between cases (11.67±11.96) and controls (4.65 ± 0.48). But, no significant difference in the different genotypes of breast cancer patients(p=0.83). Conclusion Survivin promoter-31 G/C polymorphism is associated with the risk of developing breast cancer. C allele at position-31G/C in the promoter region of the survivin gene increases an individual's susceptibility to breast cancer. As regard the level of p53 antibodies, there was a significant difference between cases and controls. But, no significant difference in the different genotypes of breast cancer patients .The presence of p53 Abs it could be a useful marker to complement routine prognostic factors in breast cancer patients.