DNA repair polymorphisms influence the risk of second neoplasm after treatment of childhood acute lymphoblastic leukemia

摘要

Purpose Patients treated for childhood acute lympho-blastic leukemia (ALL) are considered to be at increased risk of developing second neoplasm. The aim of our study was to identify DNA repair polymorphisms contributing to the risk of second neoplasm in clinically well-characterized Slovenian patients treated for childhood ALL. Methods Pediatric patients diagnosed with ALL between 1971 and 2001 were included in the study. According to the identified clinical risk factors for second neoplasm, a matched set of cases with second neoplasm and controls was selected and genotyped for 11 DNA repair polymorphisms. Results Among 359 pediatric patients with ALL, 20 second neoplasms were observed. The dose of radiotherapy (P = 0.011), administration of epipodophyllotoxins (P = 0.006), and the dose of anthracyclines (P < 0.001) showed a significant association with the risk of second neoplasm. Among genetic factors, we observed a significant association of NBN 1197G allele with increased risk of second neoplasms (RR = 4.36; 95 % CI: 1.19-15.98; P = 0.026), while the risk was decreased in carriers of XRCC3-316G allele compared with patients with wild-type genotype (RR = 0.20; 95 % CI: 0.04-0.99; P = 0.049). Conclusions Our results suggest an important role of NBN 1197A>G and XRCC3-316A>G polymorphisms in the development of second neoplasm in patients treated for childhood ALL.