Determination of apoptosis-related polymorphisms in breast cancer patients

Introduction Breast cancer (BC) remains the most common oncological disease and a leading cause of cancer death among women worldwide [1]. Studies have shown that single nucleotide polymorphisms (SNPs) can cause alterations in gene expression and play a significant role in various cancers [2]. Since apoptosis is a critical process in BC pathogenesis, the analysis of SNPs in genes involved in this process can provide valuable insights into the mechanisms of BC that are not fully understood [3]. Aim The aim of this study was to analyze SNPs in apoptosis-related genes using whole-exome sequencing (WES) and evaluate the associations of selected SNPs with BC phenotype and prognosis. Methods The cohort consisted of 139 BC patients from the Hospital of Lithuanian University of Health Sciences Kaunas Clinics. For SNPs analysis, genomic DNA was extracted from peripheral blood. WES was performed on 52 randomly selected BC patients. The obtained data were used to analyze polymorphisms in 44 apoptosis-related genes (such as BBCL, TNFRSF, CASP, FASL, etc.) using Franklin platform by Genoox. Missense or UTR variants with a frequency of 5-20% (according to the 1000 Genomes Project) were selected and genotyped in the total study cohort using real-time PCR. Associations between polymorphisms and BC phenotype and prognosis were analyzed. Results In this study only 5 missense variants in apoptosis-related genes with a frequency of 5-20% were identified using WES: TNFRSF10B rs1047266, TNFRSF25 rs11800462, CASP7 rs11555408, CASP8 rs1045485, and BIRC7 rs1077019. Genotyping results of 139 BC patients showed that there were no statistically significant associations between the studied polymorphisms in allelic and genotypic models and tumor pathomorphological features and prognosis, including TNM status, receptor (ER, PR, HER2) status, progression, and death (p>0.05). Conclusions We identified 5 missense polymorphisms in apoptosis-related genes, however, their effect on BC pathogenesis was non-significant.