Polymorphisms rs4673 and rs28714259 in predicting anthracycline-mediated cardiotoxicity in patients with breast cancer

makes it possible to improve the quality of life and life expectancy of patients with cancer, anthracycline
antibio tics retain their relevance, both for scientifi c research and for clinical practice.
However, the therapeutic effi cacy of anthracyclines is associated with the development of various
complications, among which the most common is cardiotoxicity. Our study was dedicated
to searching for possible associations between rs4673 and rs28714259 single nucleotide
polymorphisms (SNPs) and the risk of cardiotoxicity in breast cancer patients who underwent
anthracycline-containing chemotherapy. Materials and methods: The study included 256 patients
with a dia gnosis of breast cancer without dia gnosed cardiovascular changes who were
treated at the National Medical Research Center of Oncology in Rostov-on-Don in 2019–2020.
For SNP genotyping, DNA was extracted from blood and high resolution melting analysis was
performed. The presence of SNPs was confi rmed by Sanger sequencing. Results: The presence
of the T-allele rs4673 increased the risk of cardiotoxicity in breast cancer patients 6.49× (95%
CI 1.48–28.53; P = 0.002), and the presence of the A-allele rs28714259 increased the risk 3.27×
(95% CI 1.23–8.75; P = 0.026). For tests based on genotyping rs4673 and rs28714259 SNPs, the
areas under the receiver operating characteristic (ROC) curves were equal to 71.9% and 76.3%,
respectively. The two-locus SNP-SNP model turned out to be statistically signifi cant: the training
balanced accuracy was 0.77; similarly, the testing balanced accuracy, and the cross-validation
consistency was 10/ 10. Conclusion: Our study confi rmed the predictive value of genetic
tests based on the determination of the rs4673 and rs28714259 SNPs. Genotyping of both
SNPs will signifi cantly improve the accuracy of predicting the development of cardiotoxicity
against the background of anthracycline-containing therapy and timely identify the risk group
of breast cancer patients for whom it is necessary to adjust the therapeutic strategy.