Vaitiekus Domas, Muckiene Gintare, Verikas Dovydas, Vaitiekiene Audrone, Astasauskaite Skaiste, Gerbutavicius Rolandas, Bartnykaite Agne, Ugenskienė Rasa, Jurkevičius Renaldas, Juozaitytė Elona
Clinic of Oncology and Hematology, Institute of Oncology, Faculty of Medicine, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Clinical Department of Cardiology, Medical Academy, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Int J Mol Sci. 2025 Apr 25;26(9):4051. doi: 10.3390/ijms26094051.
Breast cancer is the most common cancer in women worldwide. Anthracyclines (doxorubicin, epirubicin, daunorubicin, idarubicin) are among the most used drugs for the treatment of breast cancer. Unfortunately, anthracyclines cause cardiotoxicity, which is a limiting factor for its use, and the lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. In our study, we focused on acute and subacute heart damage. One of the main factors is a genetic predisposition, which determines individual susceptibility to anthracycline cardiotoxicity. The main idea of this study was, for the first time, to evaluate drug metabolism-related genes as a risk factor for developing cardiovascular toxicity in breast cancer patients. The main objective of our study was to identify the impact of drug metabolism-related gene SNPs on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. The data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in an outpatient clinic were analyzed, and SNP RT-PCR tests were performed. The drug metabolism-related gene variants rs10426377, rs17863783, rs9024, rs1056892, rs1883112, and rs1049255 did not reach a statistically important impact on ABCC in multivariate logistic regression analysis. However, we identified that rs1883112 had a risk reduction tendency for ABCC (OR = 0.49, 95% CI 0.27-0.87, = 0.015). Our findings suggest that some SNPs, such as , may be associated with a reduced risk of cardiotoxicity, while no variants in this study showed a statistically significant increased risk. Even though, rs1883112 showed a risk reduction tendency, suggesting the potential for personalized risk stratification. We can conclude that multiple genes are involved in ABCC, with different impacts, and it is unlikely that there is a single driver gene in ABCC pathogenesis.
乳腺癌是全球女性中最常见的癌症。蒽环类药物（多柔比星、表柔比星、柔红霉素、伊达比星）是治疗乳腺癌最常用的药物之一。不幸的是，蒽环类药物会导致心脏毒性，这是其使用的一个限制因素，而蒽环类药物的终身累积剂量是心脏毒性的主要危险因素。在我们的研究中，我们关注急性和亚急性心脏损伤。其中一个主要因素是遗传易感性，它决定了个体对蒽环类药物心脏毒性的易感性。本研究的主要思路是首次评估药物代谢相关基因作为乳腺癌患者发生心血管毒性的危险因素。我们研究的主要目的是确定药物代谢相关基因单核苷酸多态性（SNP）对乳腺癌患者基于多柔比星化疗期间和/或之后亚临床心脏损伤发生的影响。分析了81例在门诊接受基于多柔比星化疗的乳腺癌女性的数据，并进行了SNP逆转录聚合酶链反应（RT-PCR）检测。在多变量逻辑回归分析中，药物代谢相关基因变异rs10426377、rs17863783、rs9024、rs1056892、rs1883112和rs1049255对ABCC未产生统计学上的重要影响。然而，我们发现rs1883112对ABCC有降低风险的趋势（比值比[OR]=0.49,95%置信区间[CI]0.27 - 0.87，P=0.015）。我们的研究结果表明，一些SNP，如rs1883112，可能与心脏毒性风险降低有关，而本研究中没有变异显示出统计学上显著增加的风险。尽管rs1883112显示出降低风险的趋势，提示了个性化风险分层的可能性。我们可以得出结论，多个基因参与了ABCC，且影响各异，在ABCC发病机制中不太可能存在单一的驱动基因。
