SUMMRY

Breast cancer (BC) is a complex disease which is influenced by a number of factors, including the environment, sociobiology, family history, hormones, obesity, and the immune system of the individual. Despite the fact that only 5–6% of BC cases are inherited, genetic mutations are one of the most predictable risk factors that contribute to BC development, with many studies reporting different genetic variants in critical genes that may induce BC onset.

Understanding the role of the immune system for tumor development has been the central focus of tumor immunology since its inception. The immune system and cancer cells share complex interactions during tumor development. In multicellular organisms, cytokines are intercellular mediators that regulate survival, growth, differentiation, and the effector functions of cells

Interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF), and Interleukin-4 (IL-4) serum levels and genetic mutations in BC patients were assessed in the current study. The serum levels of the examined cytokines in 40 BC patients and 40 healthy controls were assessed using the ELISA technique. In order to identify genotype variants of the IL-1β, IL-4, and VEGF genes in 40 formalin fixed paraffin embedded (FFPE) samples with BC and 10 FFPE samples from healthy women’s breast tissue, Sanger sequencing was used.

According to this study, BC patients had significantly lower serum concentrations of IL-4 and significantly higher quantities of the tumor markers, CA15-3, IL-1β, and VEGF. In terms of gene alterations, a total of 21 mutations in three trialed genes (8 in IL-1β, 10 in IL-4, and 3 in VEGF) were found in BC patients, among these 17 novel mutations were recorded. Extensively, in IL-1β, all genomic mutations belong to the nucleotide substitution type, (A>AG, A>AT, C>CT and C>CG), only two mutations have been reported previously in external public database. Meanwhile, as far as we know, none of the other mutational changes of IL-1β gene have been recorded in external databases. The evaluation of IL-4 gene sequencing data showed the maximum rate of mutations among the 3 genes and two types of genetic mutations were detected: Substitutions (A>AT, A>AG, G>GA and C>CT) and deletions (T and CA), only two mutations have been reported previously in external databases. Regarding VEGF, the obtained data revealed that all genomic mutations belong to the type of nucleotide substitution (A>AG and C>CT) and on the other hand, as far as we know, all the mutations have not been reported in external databases. However, the Sanger sequencing of control samples show no mutations in the cytokines used in this study.