Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Validation of the BOADICEA model for predicting the likelihood of carrying pathogenic variants in eight breast and ovarian cancer susceptibility genes

Møller, Nanna Bæk ; Boonen, Desirée Sofie ; Feldner, Elisabeth Simone ; Hao, Qin ; Larsen, Martin ; Lænkholm, Anne Vibeke ; Borg, Åke LU ; Kvist, Anders LU ; Törngren, Therese LU and Jensen, Uffe Birk , et al. (2023) In Scientific Reports 13(1).
Abstract

BOADICEA is a comprehensive risk prediction model for breast and/or ovarian cancer (BC/OC) and for carrying pathogenic variants (PVs) in cancer susceptibility genes. In addition to BRCA1 and BRCA2, BOADICEA version 6 includes PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D. To validate its predictions for these genes, we conducted a retrospective study including 2033 individuals counselled at clinical genetics departments in Denmark. All counselees underwent comprehensive genetic testing by next generation sequencing on suspicion of hereditary susceptibility to BC/OC. Likelihoods of PVs were predicted from information about diagnosis, family history and tumour pathology. Calibration was examined using the observed-to-expected ratio (O/E)... (More)

BOADICEA is a comprehensive risk prediction model for breast and/or ovarian cancer (BC/OC) and for carrying pathogenic variants (PVs) in cancer susceptibility genes. In addition to BRCA1 and BRCA2, BOADICEA version 6 includes PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D. To validate its predictions for these genes, we conducted a retrospective study including 2033 individuals counselled at clinical genetics departments in Denmark. All counselees underwent comprehensive genetic testing by next generation sequencing on suspicion of hereditary susceptibility to BC/OC. Likelihoods of PVs were predicted from information about diagnosis, family history and tumour pathology. Calibration was examined using the observed-to-expected ratio (O/E) and discrimination using the area under the receiver operating characteristics curve (AUC). The O/E was 1.11 (95% CI 0.97–1.26) for all genes combined. At sub-categories of predicted likelihood, the model performed well with limited misestimation at the extremes of predicted likelihood. Discrimination was acceptable with an AUC of 0.70 (95% CI 0.66–0.74), although discrimination was better for BRCA1 and BRCA2 than for the other genes in the model. This suggests that BOADICEA remains a valid decision-making aid for determining which individuals to offer comprehensive genetic testing for hereditary susceptibility to BC/OC despite suboptimal calibration for individual genes in this population.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
13
issue
1
article number
8536
publisher
Nature Publishing Group
external identifiers
  • pmid:37237042
  • scopus:85160223793
ISSN
2045-2322
DOI
10.1038/s41598-023-35755-8
language
English
LU publication?
yes
id
953f00b7-f196-4839-a6ce-717da41b817b
date added to LUP
2023-08-17 10:14:43
date last changed
2024-04-20 00:52:35
@article{953f00b7-f196-4839-a6ce-717da41b817b,
  abstract     = {{<p>BOADICEA is a comprehensive risk prediction model for breast and/or ovarian cancer (BC/OC) and for carrying pathogenic variants (PVs) in cancer susceptibility genes. In addition to BRCA1 and BRCA2, BOADICEA version 6 includes PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D. To validate its predictions for these genes, we conducted a retrospective study including 2033 individuals counselled at clinical genetics departments in Denmark. All counselees underwent comprehensive genetic testing by next generation sequencing on suspicion of hereditary susceptibility to BC/OC. Likelihoods of PVs were predicted from information about diagnosis, family history and tumour pathology. Calibration was examined using the observed-to-expected ratio (O/E) and discrimination using the area under the receiver operating characteristics curve (AUC). The O/E was 1.11 (95% CI 0.97–1.26) for all genes combined. At sub-categories of predicted likelihood, the model performed well with limited misestimation at the extremes of predicted likelihood. Discrimination was acceptable with an AUC of 0.70 (95% CI 0.66–0.74), although discrimination was better for BRCA1 and BRCA2 than for the other genes in the model. This suggests that BOADICEA remains a valid decision-making aid for determining which individuals to offer comprehensive genetic testing for hereditary susceptibility to BC/OC despite suboptimal calibration for individual genes in this population.</p>}},
  author       = {{Møller, Nanna Bæk and Boonen, Desirée Sofie and Feldner, Elisabeth Simone and Hao, Qin and Larsen, Martin and Lænkholm, Anne Vibeke and Borg, Åke and Kvist, Anders and Törngren, Therese and Jensen, Uffe Birk and Boonen, Susanne Eriksen and Thomassen, Mads and Terkelsen, Thorkild}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Validation of the BOADICEA model for predicting the likelihood of carrying pathogenic variants in eight breast and ovarian cancer susceptibility genes}},
  url          = {{http://dx.doi.org/10.1038/s41598-023-35755-8}},
  doi          = {{10.1038/s41598-023-35755-8}},
  volume       = {{13}},
  year         = {{2023}},
}