Association of angiogenesis and inflammation-related gene functional polymorphisms with early-stage breast cancer prognosis

• Published in: Oncology letters 2020-06, Vol.19 (6), p.3687-3700
• Main Authors: Korobeinikova, Erika, Ugenskiene, Rasa, Insodaite, Ruta, Rudzianskas, Viktoras, Jaselske, Evelina, Poskiene, Lina, Juozaityte, Elona
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis; Breast cancer; Cancer genetics; Cancer metastasis; Cancer research; Cancer therapies; Cell adhesion & migration; Cell growth; Chromosomes; Cytokines; Deoxyribonucleic acid; Development and progression; Diseases; DNA; Epidermal growth factor; Genes; Genetic aspects; Genetic polymorphisms; Genomics; Genotypes; Health aspects; Health sciences; Hospitals; Inflammation; Medical prognosis; Metastasis; Mortality; Oncology; Polymerase chain reaction; Prognosis; Proteins; Scientific equipment industry; Single nucleotide polymorphisms; Statistical analysis; Studies; Survival analysis; Tumors; Vascular endothelial growth factor; Womens health
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2020.11521

Genetic variations in inflammation- and angiogenesis-related genes may alter the coded protein level and impact the pathogenesis of breast cancer (BC). The present study investigated the association of functional single nucleotide polymorphisms (SNPs) in the and genes with the early-stage BC phenotype and survival. Genomic DNA and clinical data were collected for 202 adult Eastern European (Lithuanian) women with primary I-II stage BC. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Nine and polymorphisms were analysed. The and haplotypes were inferred using Phase software. Patients were prospectively followed-up for recurrence, occurrence of metastasis and mortality until April 30, 2019. All studied genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the 1,000 Genomes project Phase 3 dataset for European population. Significant associations of the studied SNPs with clinicopathologic variables were observed between rs1800587 C allele and larger primary tumour size; rs1800797 A allele, rs1800797 GA genotype, rs1800795 C allele, (rs1800797-re1800795) AC diplotype and hormonal receptor-positive disease; rs1800797 A allele and HER2 negative status. In univariate Cox survival analysis, rs1800587 CC and rs1800797 GG genotype carriers exhibited worse disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS). The rs1800795 GG genotype was associated with worse OS. (rs1800797, rs1800795) GG/GG diplotype carriers had shorter MFS and OS. Multivariate Cox survival analysis revealed that the rs1800587 CC genotype was an independent negative prognostic factor for DFS, MFS and OS, and the IL6 GG/GG diplotype was an independent negative prognostic factor for MFS and OS. According to the present study, functional SNPs in the and genes may contribute to the identification of patients at higher risk of BC recurrence, development of metastases and worse OS among early-stage patients with BC.