The Connection of Polymorphisms–238A/G TNF and Ile655Val HER2 Influences the Risk and Molecular Features of Breast Cancer

Abstract

Inflammation and hormonal and growth factors play an important role in the development of breast cancer (BC). Genes TNF, ESR1, and HER2 have polymorphisms that affect the level of transcription or activity of their protein products. The objective was to evaluate the effect of functional polymorphisms of these genes on the clinical and molecular features of BC. The study included 140 patients with primary BC without distant metastases. The concentrations of serum sTNF were determined for 111 BC patients. Additionally, we used archival DNA samples with known genotype–238A/G TNF from BC patients and the control- group women. Polymorphisms–238G/A TNF,–308G/A TNF,–397C/T ESR1, and Ile655Val HER2 were determined by PCR. The analysis of the data revealed the connection of AG–238TNF genotype with the Luminal A molecular subtype of tumor. A synchronous decrease of the index of proliferation Ki67 and serum level of sTNF was noted for AG–238TNF and IleVal HER2 genotypes. At the same time, carriers of the AG–238TNF more often had IleVal HER2 genotype than did carriers of GG–238TNF (70 and 32%, respectively; p = 0.032). In general, the distribution of HER2 genotypes in carriers of the AG–238TNF BC patients differed from the GG–238TNF BC patients and from both genotypes (AG and GG–238TNF) of the control group. The dependence was confirmed on archived DNA samples from BC patients with AG–238TNF genotype. There was no connection of polymorphism 397C/T ESR1 with ER status of the tumor and no connection of polymorphism Ile655Val HER2 with overexpression and/or amplification of the cell receptor Her2. Thus, the polymorphism–238G/A TNF is associated with Ile655Val HER2 and affects the molecular characteristics of BC. It is suggested that the Val HER2 may be a risk factor for BC for carriers of the AG–238TNF genotype.