. 2023 May;60(5):417-429.

doi: 10.1136/jmg-2022-108898. Epub 2022 Nov 21.

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

Helen Hanson^{1

2}, Anjana Kulkarni³, Lucy Loong², Grace Kavanaugh², Bethany Torr², Sophie Allen², Munaza Ahmed⁴, Antonis C Antoniou⁵, Ruth Cleaver⁶, Tabib Dabir⁷, D Gareth Evans^{8

9}, Ellen Golightly¹⁰, Rosalyn Jewell¹¹, Kelly Kohut¹², Ranjit Manchanda^{13

14

15}, Alex Murray¹⁶, Jennie Murray¹⁷, Kai-Ren Ong¹⁸, Adam N Rosenthal¹⁹, Emma Roisin Woodward^{9

20}, Diana M Eccles²¹, Clare Turnbull², Marc Tischkowitz²²; Consensus meeting attendees; Fiona Lalloo²⁰

Collaborators, Affiliations

Collaborators

Consensus meeting attendees:
Julian Barwell, Cheryl Berlin, Helen Bolton, Angela Brady, Karen Cadoo, Helena Carley, Oonagh Claber, Jackie Cook, Ellen Copson, Rosemarie Davidson, Alan Donaldson, Miranda Durkie, Angela George, Sadaf Ghaem-Maghami, Rachael Mein, Stephanie Greville-Heygate, David Goudie, Sarah Hamilton, Rachel Harrison, Lara Hawkes, Kate Henwood, Debby Holloway, Tracey Irvine, Rema Iyer, Atiyah Kamran, Zoe Kemp, Zosia Miedzybrodzka, Terri McVeigh, Selina Moss Davies, Hannah Musgrave, Sian Nisbet, Paul Pharoah, Marie-Claire Platt, Imran Rafi, Gillian Rea, Sukhwinder Sahota, Aarti Sharma, Lucy Side, Katherine Smith, Katie Snape, Hooman Soleymani Majd, Bev Speight, Anil Tailor, William Teh, Karin Williamson

Affiliations

¹ South West Thames Regional Genetic Services, St George's University Hospitals NHS Foundation Trust, London, UK helen.hanson@stgeorges.nhs.uk.
² Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
³ Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁴ North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK.
⁵ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁶ Department of Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
⁷ Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, UK.
⁸ Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
⁹ Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK.
¹⁰ Lothian Menopause Service, Chalmers Sexual Health Centre, Edinburgh, UK.
¹¹ Department of Clinical Genetics, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹² South West Thames Regional Genetic Services, St George's University Hospitals NHS Foundation Trust, London, UK.
¹³ Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, London, UK.
¹⁴ Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK.
¹⁵ Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK.
¹⁶ All Wales Medical Genomics Services, University Hospital of Wales, Cardiff, UK.
¹⁷ South East Scotland Clinical Genetics Service, Western General Hospital, Edinburgh, UK.
¹⁸ West Midlands Regional Genetics Service, Birmingham Women's Hospital, Birmingham, UK.
¹⁹ Department of Gynaecological Oncology, University College London Hospitals NHS Foundation Trust, London, UK.
²⁰ Manchester Centre for Genomic Medicine, Central Manchester NHS Foundation Trust, Manchester, UK.
²¹ Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
²² Department of Medical Genetics, University of Cambridge, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK.

PMID: 36411032
PMCID: PMC10176381
DOI: 10.1136/jmg-2022-108898

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

Helen Hanson et al. J Med Genet. 2023 May.

. 2023 May;60(5):417-429.

doi: 10.1136/jmg-2022-108898. Epub 2022 Nov 21.

Authors

Collaborators

Consensus meeting attendees:
Julian Barwell, Cheryl Berlin, Helen Bolton, Angela Brady, Karen Cadoo, Helena Carley, Oonagh Claber, Jackie Cook, Ellen Copson, Rosemarie Davidson, Alan Donaldson, Miranda Durkie, Angela George, Sadaf Ghaem-Maghami, Rachael Mein, Stephanie Greville-Heygate, David Goudie, Sarah Hamilton, Rachel Harrison, Lara Hawkes, Kate Henwood, Debby Holloway, Tracey Irvine, Rema Iyer, Atiyah Kamran, Zoe Kemp, Zosia Miedzybrodzka, Terri McVeigh, Selina Moss Davies, Hannah Musgrave, Sian Nisbet, Paul Pharoah, Marie-Claire Platt, Imran Rafi, Gillian Rea, Sukhwinder Sahota, Aarti Sharma, Lucy Side, Katherine Smith, Katie Snape, Hooman Soleymani Majd, Bev Speight, Anil Tailor, William Teh, Karin Williamson

Affiliations

¹ South West Thames Regional Genetic Services, St George's University Hospitals NHS Foundation Trust, London, UK helen.hanson@stgeorges.nhs.uk.
² Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
³ Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁴ North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK.
⁵ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁶ Department of Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
⁷ Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, UK.
⁸ Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
⁹ Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK.
¹⁰ Lothian Menopause Service, Chalmers Sexual Health Centre, Edinburgh, UK.
¹¹ Department of Clinical Genetics, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹² South West Thames Regional Genetic Services, St George's University Hospitals NHS Foundation Trust, London, UK.
¹³ Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, London, UK.
¹⁴ Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK.
¹⁵ Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK.
¹⁶ All Wales Medical Genomics Services, University Hospital of Wales, Cardiff, UK.
¹⁷ South East Scotland Clinical Genetics Service, Western General Hospital, Edinburgh, UK.
¹⁸ West Midlands Regional Genetics Service, Birmingham Women's Hospital, Birmingham, UK.
¹⁹ Department of Gynaecological Oncology, University College London Hospitals NHS Foundation Trust, London, UK.
²⁰ Manchester Centre for Genomic Medicine, Central Manchester NHS Foundation Trust, Manchester, UK.
²¹ Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
²² Department of Medical Genetics, University of Cambridge, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK.

PMID: 36411032
PMCID: PMC10176381
DOI: 10.1136/jmg-2022-108898

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.

Keywords: Clinical Decision-Making; Delivery of Health Care; Genetic Carrier Screening; Genetic Predisposition to Disease; Gynecology.

PubMed Disclaimer

Conflict of interest statement

Competing interests: HH received honoraria from AstraZeneca for advisory roles. CT received honoraria from AstraZeneca and Roche for advisory roles, which were donated in full to charity (https://tukongote.com/, registration number 11511580, charity number 1186151). RM declares research funding from Barts & the London Charity, Rosetrees Trust, GSK, Eve Appeal, CRUK and Yorkshire Cancer Research outside this work; and honorarium for advisory board membership from AstraZeneca/MSD/GSK/EGL. DME was in receipt of research funding from AstraZeneca. ANR had prior consultancy arrangements with Abcodia and Everything Genetic. ACA was listed as a creator of BOADICEA, which was licensed by Cambridge Enterprise for commercial purposes.

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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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

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Grants and funding

LinkOut - more resources

Medical

Research Materials