Influence of the polymorphism in candidate genes on late cardiac damage in patients treated due to acute leukemia in childhood.
Anthracyclines have contributed significantly to the increased cure rate in pediatric oncology. Cardiac toxicity is an important late effect after anthracycline treatment and is thought to occur by reactive oxygen species mediated cardiac damage. We hypothesized that deactivating variants of superoxide dismutase II (SOD2) [rs4880 (-9Val > Ala)], catalase (CAT) [rs1001179 (-262C > T) and rs10836235 (c.66 + 78C > T)], GSTT1, and GSTM1 may increase the risk of developing cardiac toxicity, in patients exposed to anthracyclines. The hypothesis was tested in a cohort of 76 long-term survivals of acute lymphoblastic leukemia in childhood. Cardiac damage was evaluated as an attributive variable and compared to gene polymorphisms. In our study group, we show statistically significant correlation between CC homozygosity for CAT (rs10836235 (c.66 + 78C > T)) and cardiac damage after anthracycline exposure (p = 0.020). We found no statistically significant correlation between cardiac damage after anthracycline exposure and deactivating variants of SOD2 [rs4880 (-9Val > Ala)], CAT [rs1001179 (-262C > T), GSTT1, and GSTM1.
Department of Hematology & Oncology, University Children's Hospital, Ljubljana, Slovenia. vladan.rajic@kclj.si
Vladan
V
Rajić
Richard
R
Aplenc
Marusa
M
Debeljak
Veronika Velensek
VV
Prestor
Natasa
N
Karas-Kuzelicki
Irena
I
Mlinaric-Rascan
Janez
J
Jazbec
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D002374:Catalase / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000235:genetics; D017741:Survivors; D014463:Ultrasonography; D055815:Young Adult; D000099156:Superoxide Dismutase 2
D018943:Anthracyclines; D002374:Catalase; D005982:Glutathione Transferase; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C413545:glutathione S-transferase T1