Role of the renin-angiotensin-aldosterone system and the glutathione S-transferase Mu, Pi and Theta gene polymorphisms in cardiotoxicity after anthracycline chemotherapy for breast carcinoma

摘要

Background: 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. Aims: 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. Methods: 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%). Conclusion: RAAS gene polymorphisms were not significantly associated with the development of cardiotoxicity. GSTM1 may be useful as a biomarker of higher risk of cardiotoxicity, as demonstrated in our cohort of patients (p=0.147).