Abstract P5-09-01: Evaluation of BCL2 sequence variant in Iranian women patients with Breast cancer

Abstract

Abstract Introduction: Despite recent advancements in the treatment and management of cancers, Breast cancer still remains the most common malignancy and second leading cause of cancer-related deaths among women in Iran. Apoptosis and cellular proliferation play role an important role during normal mammary development and carcinogenesis of the mammary gland. In normal tissues, the homeostasis between apoptosis and cell proliferation is regulated by Bcl-2 family proteins. Tumor cells tend to interfere with the mechanism of Apoptosis by activating anti apoptotic genes such as bcl-2. BCL-2 gene, located at 18q21.3 and consists of three exons and two promoters (P1 and P2), which have different functions. The second promoter, P2, is located 1,400 bp upstream of the translation initiation site and functions as a negative regulatory element to the P1 promoter. Bcl-2 is the one of the most important anti apoptotic genes. It has been shown that the −938AA genotype s associated with higher Bcl-2 expression levels in B-CLL and poor prognosis. Bcl2 gene has been also demonstrated with breast cancer development and a single nucleotide polymorphism (SNP-938C >A) has been identified recently and can provide a susceptible factor for causing breast cancer. The main objective of this study was to evaluation of the frequency of specific genetic alterations in the BCL-2 gene (−938,-758 and 21) and the risk of breast cancer in Iranian women patients with Breast cancer. Materials and Methods: Patients; 27 paired Fresh tumor and adjacent normal samples were obtained from consecutive patients with BC who underwent surgery for mama mastroctomy from IRANIAN National Tumor Bank, National Cancer Institute, Imam Khomeini Hospital Complexes, Medical Tehran University, Tehran, Iran. Histopathological examinations were performed, and all tumors were confirmed as adenocarcinoma. Mutational analysis: Fresh tumors and their adjacent were extracted for genomic DNA using the QIA amp Mini Kit according to the manufacturer's instructions. We searched DNA samples of Iranian patients for identification of SNP; −938C>A, −758T insertion in the inhibitory P2 promoter and 21A/G in exon 2 of the BCL-2 gene by means of PCR sequencing. Results and conclusions: In All cases, the frequency of genetic alterations in the BCL-2 gene (−938, −758 and 21) was 16 of 27 (59.29%) heterozygous in −938(C, A) and 5 of 27(18.51%) SNP-938 C>A, 0 of 27(0%)and 8 of 23(34.78%)heterozygous in +21(A, G)and 2 of 23(8.69%)SNP 21A>G respectively. According to our findings, point mutation in −938C and 21A alleles displayed a positive relation with increasing tumorgenesis in breast cancer. Our result indicated that the regulatory BCL2 promoter polymorphism (−938C, A) and coding BCl2 gene (21A, G) may be useful as a tumor marker for increasing tumorgenesis in Iranian women breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-09-01.