title: DNA repair polymorphisms influence the risk of second neoplasm after treatment of childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Patients treated for childhood acute lymphoblastic 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.
authors: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors: Nina
authors: N
authors: Erčulj
authors: Barbara
authors: B
authors: Faganel Kotnik
authors: Maruša
authors: M
authors: Debeljak
authors: Janez
authors: J
authors: Jazbec
authors: Vita
authors: V
authors: Dolžan
mesh_terms: D000293:Adolescent; D000483:Alleles; D018943:Anthracyclines / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D011034:Podophyllotoxin / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000235:genetics* / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; C110901:X-ray repair cross complementing protein 3; D011034:Podophyllotoxin