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

Annelot Baert (UGent) , Julie Depuydt (UGent) , Tom Van Maerken (UGent) , Bruce Poppe (UGent) , Fransiska Malfait (UGent) , Tim Van Damme (UGent) , Sylvia De Nobele (UGent) , Gianpaolo Perletti (UGent) , Kim De Leeneer (UGent) , Kathleen Claes (UGent) , et al.
(2017) ONCOLOGY REPORTS. 37(3). p.1379-1386
Author
Organization
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.
Keywords
BRCA2 mutation carriers, non-carrier relatives, ionizing radiation, micronucleus assay, chromosomal radiosensitivity, BREAST-CANCER RISK, CHEST X-RAYS, PROVEN NONCARRIERS, POSITIVE FAMILIES, NEGATIVE WOMEN, NO EVIDENCE, MAMMOGRAPHY, REPAIR, PHENOCOPIES, RADIATION

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MLA
Baert, Annelot et al. “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. Print.
APA
Baert, Annelot, Depuydt, J., Van Maerken, T., Poppe, B., Malfait, F., Van Damme, T., De Nobele, S., et al. (2017). Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay. ONCOLOGY REPORTS, 37(3), 1379–1386.
Chicago author-date
Baert, Annelot, Julie Depuydt, Tom Van Maerken, Bruce Poppe, Fransiska Malfait, Tim Van Damme, Sylvia De Nobele, et al. 2017. “Analysis of Chromosomal Radiosensitivity of Healthy BRCA2 Mutation Carriers and Non-carriers in BRCA Families with the G2 Micronucleus Assay.” Oncology Reports 37 (3): 1379–1386.
Chicago author-date (all authors)
Baert, Annelot, Julie Depuydt, Tom Van Maerken, Bruce Poppe, Fransiska Malfait, Tim Van Damme, Sylvia De Nobele, Gianpaolo Perletti, Kim De Leeneer, Kathleen Claes, and Anne Vral. 2017. “Analysis of Chromosomal Radiosensitivity of Healthy BRCA2 Mutation Carriers and Non-carriers in BRCA Families with the G2 Micronucleus Assay.” Oncology Reports 37 (3): 1379–1386.
Vancouver
1.
Baert A, Depuydt J, Van Maerken T, Poppe B, Malfait F, Van Damme T, et al. Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay. ONCOLOGY REPORTS. 2017;37(3):1379–86.
IEEE
[1]
A. Baert et al., “Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay,” ONCOLOGY REPORTS, vol. 37, no. 3, pp. 1379–1386, 2017.
@article{8507493,
  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.},
  author       = {Baert, Annelot and Depuydt, Julie and Van Maerken, Tom and Poppe, Bruce and Malfait, Fransiska and Van Damme, Tim and De Nobele, Sylvia and Perletti, Gianpaolo and De Leeneer, Kim and Claes, Kathleen and Vral, Anne},
  issn         = {1021-335X},
  journal      = {ONCOLOGY REPORTS},
  keywords     = {BRCA2 mutation carriers,non-carrier relatives,ionizing radiation,micronucleus assay,chromosomal radiosensitivity,BREAST-CANCER RISK,CHEST X-RAYS,PROVEN NONCARRIERS,POSITIVE FAMILIES,NEGATIVE WOMEN,NO EVIDENCE,MAMMOGRAPHY,REPAIR,PHENOCOPIES,RADIATION},
  language     = {eng},
  number       = {3},
  pages        = {1379--1386},
  title        = {Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay},
  url          = {http://dx.doi.org/10.3892/or.2017.5407},
  volume       = {37},
  year         = {2017},
}

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