Association of rs28714259 polymorphism with a risk of early-onset chronic anthracycline-mediated cardiotoxicity in patients with breast cancer.

Abstract

e13504 Background: Numerous pharmacogenetic studies have led to the identification of genetic polymorphisms associated not only with the development of cardiovascular disease, but also increase the risk of complications due to the use of anthracycline drugs, widely used in the treatment of cancer. The purpose of this study was to assess the prevalence of rs28714259 polymorphism and to study possible correlation with anthracycline-mediated cardiotoxicity (AMC). Methods: The study included 173 Caucasian patients (median age 55 years) with a diagnosis of breast cancer without diagnosed cardiovascular pathology who underwent treatment in the RRIO, Rostov-on-Don in 2019. For genotyping of SNP rs28714259, DNA was extracted from blood using DNA-sorb-B (AmpliSens, Russia) and HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphism was confirmed by Sanger sequencing with a Genetic Analyzer 3500 (ABI, USA). The obtained results were compared with European population (1000 Genome). Results: 13 patients (7.5%) with an early-onset of chronic AMC were founded after three courses of chemotherapy. The allelic frequency rs28714259 was 0.079, the frequency of AG genotypes was 0.135, and AA was 0.012. It was shown that the presence of this SNP leads to an increase risk of cardiovascular pathology at an early stage by more than 4 times (OR = 4.186, p = 0.006). In addition, when comparing with the European population, the highest probability of developing early-onset chronic AMC was determined for patients with the AA genotype (more than 22 times, p = 0.001). Conclusions: In this study, a statistically significant association of rs28714259 presence with developing early-onset chronic AMC was revealed, which seems promising for the early determination of the risk group in the management of cancer patients.