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UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes; RAD51C, RAD51D, BRIP1 and PALB2

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes; RAD51C, RAD51D, BRIP1 and PALB2
UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes; RAD51C, RAD51D, BRIP1 and PALB2
Germline pathogenic variants (GPVs) in the cancer predisposition genes BRCA1, BRCA2, MLH1, MSH2, MSH6, BRIP1, PALB2, RAD51D and RAD51C are identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV in BRCA1, BRCA2, MLH1, MSH2 and MSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV in BRIP1, PALB2, RAD51D and RAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition of RAD51C and RAD51D as OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management of BRIP1, PALB2, RAD51D and RAD51C carriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting.
0022-2593
Hanson, Helen
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Kulkarni, Anju
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Loong, Lucy
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Kavanaugh, Grace
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Torr, Bethany
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Allen, Sophie
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Antoniou, Antonis C.
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Cleaver, Ruth
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Dabir, Tabib
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Evans, D. Gareth
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Golightly, Ellen
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Jewell, Rosalyn
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Kohut, Kelly Elizabeth
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Manchanda, Ranjit
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Murray, Alex
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Murry, Jennie
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Ong, Kai-Ren
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Rosenthal, Adam N.
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Woodward, Emma Roisin
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Eccles, Diana
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Turnbull, Clare
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Tischkowitz, Marc
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Hanson, Helen
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Kulkarni, Anju
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Loong, Lucy
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Kavanaugh, Grace
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Torr, Bethany
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Allen, Sophie
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Antoniou, Antonis C.
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Cleaver, Ruth
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Dabir, Tabib
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Evans, D. Gareth
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Golightly, Ellen
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Jewell, Rosalyn
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Kohut, Kelly Elizabeth
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Manchanda, Ranjit
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Murray, Alex
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Murry, Jennie
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Ong, Kai-Ren
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Rosenthal, Adam N.
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Woodward, Emma Roisin
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Eccles, Diana
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Turnbull, Clare
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Tischkowitz, Marc
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Hanson, Helen, Kulkarni, Anju, Loong, Lucy, Kavanaugh, Grace, Torr, Bethany, Allen, Sophie, Antoniou, Antonis C., Cleaver, Ruth, Dabir, Tabib, Evans, D. Gareth, Golightly, Ellen, Jewell, Rosalyn, Kohut, Kelly Elizabeth, Manchanda, Ranjit, Murray, Alex, Murry, Jennie, Ong, Kai-Ren, Rosenthal, Adam N., Woodward, Emma Roisin, Eccles, Diana, Turnbull, Clare and Tischkowitz, Marc (2022) UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes; RAD51C, RAD51D, BRIP1 and PALB2. Journal of Medical Genetics, [108898]. (doi:10.1136/jmg-2022-108898).

Record type: Article

Abstract

Germline pathogenic variants (GPVs) in the cancer predisposition genes BRCA1, BRCA2, MLH1, MSH2, MSH6, BRIP1, PALB2, RAD51D and RAD51C are identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV in BRCA1, BRCA2, MLH1, MSH2 and MSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV in BRIP1, PALB2, RAD51D and RAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition of RAD51C and RAD51D as OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management of BRIP1, PALB2, RAD51D and RAD51C carriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting.

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More information

Accepted/In Press date: 25 October 2022
e-pub ahead of print date: 25 October 2022
Published date: 21 November 2022
Additional Information: Funding: HH, FL, BT, SA and LL are supported by Cancer Research CRUK Catalyst Award, CanGene-CanVar (C61296/A27223). DGE and ERW are supported by the Manchester NIHR Biomedical Research Centre. MT was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). ANR was supported by the NIHR Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust and University College London.

Identifiers

Local EPrints ID: 472272
URI: http://eprints.soton.ac.uk/id/eprint/472272
ISSN: 0022-2593
PURE UUID: 8f1e25d6-03b2-486a-8caa-4918407e6725
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 30 Nov 2022 17:43
Last modified: 17 Mar 2024 02:36

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Contributors

Author: Helen Hanson
Author: Anju Kulkarni
Author: Lucy Loong
Author: Grace Kavanaugh
Author: Bethany Torr
Author: Sophie Allen
Author: Antonis C. Antoniou
Author: Ruth Cleaver
Author: Tabib Dabir
Author: D. Gareth Evans
Author: Ellen Golightly
Author: Rosalyn Jewell
Author: Kelly Elizabeth Kohut
Author: Ranjit Manchanda
Author: Alex Murray
Author: Jennie Murry
Author: Kai-Ren Ong
Author: Adam N. Rosenthal
Author: Emma Roisin Woodward
Author: Diana Eccles ORCID iD
Author: Clare Turnbull
Author: Marc Tischkowitz

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