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

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Abstract

Purpose

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.

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Acknowledgments

This work was financially supported by The Slovenian Research Agency (ARRS Grants No. P1-0170, J3-4220, and P3-0343). Nina Erculj was the recipient of the Slovenian National L’Oreal-UNESCO For Women In Science Programme 2012 Award.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia

    Nina Erčulj & Vita Dolžan

  2. Department of Hematology and Oncology, University Children’s Hospital, University Medical Centre, Bohoričeva ulica 20, 1000, Ljubljana, Slovenia

    Barbara Faganel Kotnik & Janez Jazbec

  3. University Children’s Hospital, Centre for Medical Genetics, University Medical Centre, Vrazov trg 1, 1000, Ljubljana, Slovenia

    Maruša Debeljak

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  1. Nina Erčulj
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  2. Barbara Faganel Kotnik
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Correspondence to Vita Dolžan.

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Erčulj, N., Faganel Kotnik, B., Debeljak, M. et al. DNA repair polymorphisms influence the risk of second neoplasm after treatment of childhood acute lymphoblastic leukemia. J Cancer Res Clin Oncol 138, 1919–1930 (2012). https://doi.org/10.1007/s00432-012-1265-4

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