Gándara-Mireles Jesús Alonso, Lares-Asseff Ismael, Reyes Espinoza Elio Aarón, Blanco Javier G, González Font Antonio Emilio, Córdova Hurtado Lourdes Patricia, Castañeda Verónica Loera, Fierro Ignacio Villanueva, Romero Leslie Patrón, Reyes Horacio Almanza
Academia de Genómica, Instituto Politécnico Nacional, CIIDIR-Unidad, Durango, Mexico.
Red Latinoamericana de Implementación y Validación de Guías Clínicas Farmacogenómicas (RELIVAF-CYTED).
Pharmacogenet Genomics. 2021 Jul 1;31(5):108-115. doi: 10.1097/FPC.0000000000000428.
Cardiotoxicity is a frequent complication secondary to the use of anthracyclines for cancer chemotherapy. Evidence suggests that certain polymorphic genetic variants modify the risk for anthracycline-related cardiotoxicity. Reports documenting the impact of genetic polymorphisms on anthracycline-cardiotoxicity risk in pediatric patients with cancers from Latin American countries are scarce. The objective of this study was to evaluate associations between NCF4 rs1883112, CBR3 rs1056892 and ABCC1 rs3743527 genotype status and echocardiographic parameters indicative of anthracycline-cardiotoxicity in a group of Mexican children with acute lymphoblastic leukemia (ALL).
Sixty-seven children (2-18 years old) with ALL were treated at the State Cancer Center in Durango, Mexico. NCF4, CBR3, and ABCC1 genotypes were examined by real-time PCR. Left ventricular ejection fraction and diastolic filling ratio were examined as markers of systolic and diastolic anthracycline-toxicity.
NCF4 rs1883112 genotype status was significantly associated with the risk of doxorubicin cardiotoxicity [odds ratio (OR) = 10.80, 95% confidence interval (CI) 1.69-68.98, P = 0.01]. There was a significant association between heterozygous CBR3 rs1056892 genotype status and anthracycline-cardiotoxicity risk (OR = 9.91, 95% CI 1.07-91.47, P = 0.04). Heterozygosis for the ABCC1 rs3743527 allele was associated with protection from anthracycline-cardiotoxicity (OR = 0.30, 95% CI 0.09-0.91, P = 0.03).
This pilot study suggests that selected polymorphic variants may impact the risk for anthracycline-cardiotoxicity in pediatric patients with ALL treated with a contemporary chemotherapeutic regimen in Mexico.
心脏毒性是使用蒽环类药物进行癌症化疗后的常见并发症。有证据表明，某些多态性基因变异会改变蒽环类药物相关心脏毒性的风险。记录拉丁美洲国家癌症患儿基因多态性对蒽环类药物心脏毒性风险影响的报告很少。本研究的目的是评估一组患有急性淋巴细胞白血病（ALL）的墨西哥儿童中，NCF4 rs1883112、CBR3 rs1056892和ABCC1 rs3743527基因型状态与指示蒽环类药物心脏毒性的超声心动图参数之间的关联。
67名年龄在2至18岁之间的ALL患儿在墨西哥杜兰戈州癌症中心接受治疗。通过实时聚合酶链反应检测NCF4、CBR3和ABCC1基因型。检查左心室射血分数和舒张充盈率，作为收缩期和舒张期蒽环类药物毒性的标志物。
NCF4 rs1883112基因型状态与多柔比星心脏毒性风险显著相关[比值比（OR）=10.80，95%置信区间（CI）1.69 - 68.98，P = 0.01]。杂合子CBR3 rs1056892基因型状态与蒽环类药物心脏毒性风险之间存在显著关联（OR = 9.91，95% CI 1.07 - 91.47，P = 0.04）。ABCC1 rs3743527等位基因的杂合性与预防蒽环类药物心脏毒性相关（OR = 0.30，95% CI 0.09 - 0.91，P = 0.03）。
这项初步研究表明，在墨西哥接受现代化疗方案治疗的ALL患儿中，选定的多态性变异可能会影响蒽环类药物心脏毒性的风险。
