Open Access

Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay

  • Authors:
    • Annelot Baert
    • Julie Depuydt
    • Tom Van Maerken
    • Bruce Poppe
    • Fransiska Malfait
    • Tim Van Damme
    • Sylvia De Nobele
    • Gianpaolo Perletti
    • Kim De Leeneer
    • Kathleen B.M. Claes
    • Anne Vral
  • View Affiliations

  • Published online on: January 25, 2017     https://doi.org/10.3892/or.2017.5407
  • Pages: 1379-1386
  • Copyright: © Baert et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer risk drastically increases in individuals with a heterozygous germline BRCA1 or BRCA2 mutation, while it is estimated to equal the population risk for relatives without the familial mutation (non-carriers). The aim of the present study was to use a G2 phase-specific micronucleus assay to investigate whether lymphocytes of healthy BRCA2 mutation carriers are characterized by increased radiosensitivity compared to controls without a family history of breast/ovarian cancer and how this relates to healthy non-carrier relatives. BRCA2 is active in homologous recombination, a DNA damage repair pathway, specifically active in the late S/G2 phase of the cell cycle. We found a significantly increased radiosensitivity in a cohort of healthy BRCA2 mutation carriers compared to individuals without a familial history of breast cancer (P=0.046; Mann-Whitney U test). At the individual level, 50% of healthy BRCA2 mutation carriers showed a radiosensitive phenotype (radiosensitivity score of 1 or 2), whereas 83% of the controls showed no radiosensitivity (P=0.038; one-tailed Fisher's exact test). An odds ratio of 5 (95% CI, 1.07-23.47) indicated an association between the BRCA2 mutation and radiosensitivity in healthy mutation carriers. These results indicate the need for the gentle use of ionizing radiation for either diagnostic or therapeutic use in BRCA2 mutation carriers. We detected no increased radiosensitivity in the non-carrier relatives.
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March-2017
Volume 37 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Baert A, Depuydt J, Van Maerken T, Poppe B, Malfait F, Van Damme T, De Nobele S, Perletti G, De Leeneer K, Claes KB, Claes KB, et al: Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay. Oncol Rep 37: 1379-1386, 2017
APA
Baert, A., Depuydt, J., Van Maerken, T., Poppe, B., Malfait, F., Van Damme, T. ... Vral, A. (2017). Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay. Oncology Reports, 37, 1379-1386. https://doi.org/10.3892/or.2017.5407
MLA
Baert, A., Depuydt, J., Van Maerken, T., Poppe, B., Malfait, F., Van Damme, T., De Nobele, S., Perletti, G., De Leeneer, K., Claes, K. B., Vral, A."Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay". Oncology Reports 37.3 (2017): 1379-1386.
Chicago
Baert, A., Depuydt, J., Van Maerken, T., Poppe, B., Malfait, F., Van Damme, T., De Nobele, S., Perletti, G., De Leeneer, K., Claes, K. B., Vral, A."Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay". Oncology Reports 37, no. 3 (2017): 1379-1386. https://doi.org/10.3892/or.2017.5407