Germline minisatellite mutations in survivors of childhood and young adult cancer treated with radiation

Abstract

Purpose: To investigate minisatellite germline mutation rates in survivors of childhood and young adult cancer who received radiotherapy.

Materials and methods: DNA samples from 100 families, where one parent was a cancer survivor, were analysed for mutations at eight hypervariable minisatellite loci (B6.7, CEB1, CEB15, CEB25, CEB36, MS1, MS31, MS32) by Southern hybridisation.

Results: No significant difference was observed between the paternal mutation rate of 5.6% in exposed fathers with a mean preconceptional testicular dose of 1.23 Gy (56 mutations in 998 informative alleles) and that of 5.8% in unexposed fathers (17 in 295 informative alleles). Subgrouping the exposed fathers into dose groups of <0.10 Gy, 0.10–0.99 Gy, 1.00–1.99 Gy, ≥2.00 Gy revealed no significant differences in paternal mutation rate in comparison with the unexposed fathers. Maternal mutation rates of 1.6% in cancer survivor mothers with a mean preconceptional ovarian dose of 0.58 Gy (five mutations in 304 informative alleles) and 2.1% in unexposed mothers (21 in 987 informative alleles) were not significantly different. There were no differences in minisatellite mutation rates associated with treatment with chemotherapeutic agents.

Conclusions: This study provides evidence that preconception radiotherapy for childhood or early adulthood cancer does not increase the germline minisatellite mutation rate.

Keywords:

• minisatellite
• germline mutation
• ionising radiation
• childhood and young adult cancer

Acknowledgements

We thank the Danish families for participating in this study and Brian Møllgren, Rigshospitalet, for collection of blood samples. Kelly Johnstone and Laura Carter, Westlakes Research Institute, provided technical assistance. Dosimetry data were provided by Rita Weathers, Catherine Kasper and Susan Smith, The University of Texas M.D. Anderson Cancer Center. Statistical advice was given by Robert Tarone, International Epidemiology Institute and greatly appreciated. Permissions were granted from the Danish Data Protection Agency (2001–41–1113) and the Danish Scientific Ethical Committee ([KF] 01 – 150/01 & [KF] 11 – 129/02). The work was supported by a grant from the National Cancer Institute, USA (Grant no. 5RO1 CA104666) through Vanderbilt University Medical Center, USA.

Declaration of interest:The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.