Genetic Variation of the BCL-2 Gene and its Relation to Breast Cancer in Iraqi Women

Abstract

INTRODUCTION: B-cell lymphoma-2 (BCL-2) is a key regulator of apoptosis, and its dysregulated expression contributes to cancer cell survival in several malignancies, including breast cancer. The BCL-2 gene, specifically rs2279115, has been found to significantly modulate transcriptional activity and affect BCL-2 protein expression in various tissues and diseases. Genetic differences affecting apoptotic pathways may therefore contribute to the susceptibility and progression of breast cancer. The present study aims to investigate variation in the BCL-2 genotype in humans, determine the nucleotide sequence of the gene, and determine whether this correlates with the incidence of breast cancer in 45 women.  MATERIALS AND METHODS: This case–control study included 30 women with breast cancer and 15 an age-matched group of healthy women controls. The genetic polymorphism of the BCL-2 gene in situ (rs2279115) was determined using the tetra-primer amplification refractory mutation system-polymerase chain reaction technique. Nucleotide sequencing of the amplified fragments was performed using DNA sequencing technology. Fisher’s exact test was used to compare the genotype and allele frequencies between patients and controls. RESULTS: There is genetic variation of the BCL-2 gene in patients with breast cancer, with three genotypes, CC, CT, and TT, in comparison with one genotype in healthy controls. The percentage of incidence of the T allele was 25% in breast cancer patients compared to 0% in controls. The sequencing test for the amplified BCL-2 gene reported multiple nucleotide variations in the breast cancer samples compared with controls. CONCLUSION: The present study showed a possible genetic variation with multiple mutations in the BCL-2 gene in patients with breast cancer, which needs to be confirmed by further larger cohorts.