1 Laboratory of Cancer Genetics and Translational Oncology, Oncology Division S. Croce General Hospital, Cuneo - Italy.
Int J Biol Markers. 2013 Dec 17;28(4):e336-47. doi: 10.5301/jbm.5000041.
Anthracyclines are among the most active drugs against breast cancer, but can exert cardiotoxic effects eventually resulting in congestive heart failure (CHF). Identifying breast cancer patients at high risk of developing cardiotoxicity after anthracycline therapy would be of value in guiding the use of these agents.
We determined whether polymorphisms in the renin-angiotensin-aldosterone system (RAAS) and in the glutathione S-transferase (GST) family of phase II detoxification enzymes might be useful predictors of left ventricular ejection fraction (LVEF) kinetics and risk of developing CHF. We sought correlations between the development of cardiotoxicity and gene polymorphisms in 48 patients with early breast cancer treated with adjuvant anthracycline chemotherapy.
We analyzed the following polymorphisms: p.Met235Thr and p.Thr174Met in angiotensinogen (AGT), Ins/Del in angiotensin-converting enzyme (ACE), A1166C in angiotensin II type-1 receptor (AGTR1A), c.-344T>C in aldosterone synthase (CYP11B2), p.Ile105Val in GSTP1. Additionally, we analyzed the presence or absence of the GSTT1 and GSTP1 genes. A LVEF <50% was detected at least once during the 3 years of follow-up period in 13 out of 48 patients (27.1%).
RAAS gene polymorphisms were not significantly associated with the development of cardiotoxicity. GSTM1may be useful as a biomarker of higher risk of cardiotoxicity, as demonstrated in our cohort of patients (p=0.147).
蒽环类药物是治疗乳腺癌最有效的药物之一，但最终会产生心脏毒性作用，导致充血性心力衰竭（CHF）。确定接受蒽环类药物治疗后发生心脏毒性的乳腺癌患者的高危人群，对于指导这些药物的使用具有重要意义。
我们旨在确定肾素-血管紧张素-醛固酮系统（RAAS）和谷胱甘肽 S-转移酶（GST）家族的Ⅱ相解毒酶的多态性是否可作为左心室射血分数（LVEF）动力学和心力衰竭风险的有用预测因子。我们研究了 48 例接受辅助蒽环类化疗的早期乳腺癌患者的基因多态性与心脏毒性发展之间的相关性。
我们分析了以下多态性：血管紧张素原（AGT）中的 p.Met235Thr 和 p.Thr174Met、血管紧张素转换酶（ACE）中的 Ins/Del、血管紧张素 II 型 1 受体（AGTR1A）中的 A1166C、醛固酮合酶（CYP11B2）中的 c.-344T>C、GSTP1 中的 p.Ile105Val。此外，我们还分析了 GSTT1 和 GSTP1 基因的存在或缺失。在 48 例患者中，有 13 例（27.1%）在 3 年随访期间至少有一次 LVEF<50%。
RAAS 基因多态性与心脏毒性的发展无显著相关性。GSTM1 可能是预测心脏毒性高危的有用生物标志物，这在我们的患者队列中得到了证实（p=0.147）。
