Accès ouvert déclaré
2022
article
Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes
Chey Loveday, Alice Garrett, Philip Law, Sandra Hanks, Emma Poyastro-Pearson, Julian Adlard, Julian Barwell, J. Berg, Angela F. Brady, C Brewer, C J Chapman, Jackie Cook, Alan Donaldson, Fiona Douglas, Lynn Greenhalgh, Alex Henderson, Louise Izatt, Ajith Kumar, Fiona Lalloo, Zosia Miedzybrodzka, P. Morrison, J. Paterson, Mary Porteous, Mark T. Rogers, Lyndon Walker, A. Ardern-Jones, Madiha Ahmed, Gerhardt Attard, Kent R. Bailey, Elizabeth Bancroft, Cathryn Bardsley, Desmond P.J. Barton, Madelaine Bartlett, Laura Baxter, Rachel Belk, Birgitta Bernhard, D. Timothy Bishop, Laura Boyes, N. Bradshaw, Steven R. Brant, Glen Brice, G. Bromilow, Corinne Brooks, Amanda S. Bruce, Barbara Bulman, Lucy Burgess, Joyce Campbell, Natalie Canham, B. Castle, Roseanne Cetnarskyj, Oonagh Claber, Nathan Coates, T Cole, Andrew Collins, Susan Coulson, Gillian Crawford, D. G. Crüger, Chad Cummings, Lucia D’Mello, Lauren Day, Brad Dell, CHS Dolling, Huw Dorkins, Sean R. Downing, Sean C. Drummond, C. Dubras, J Dunlop, S. Durrell, Diana Eccles, Clare M. Eddy, Melissa Edwards, Emma Edwards, J.A. Edwardson, Rosalind A. Eeles, Ian O. Ellis, Frances Elmslie, D. Gareth Evans, Barbara Gibbons, C. Gardiner, Neeti Ghali, Clare Giblin, S. L. Gibson, Sheila Goff, Selina Goodman, David Goudie, J. A. Grier, Helen Gregory, Sophia R. Halliday, Rebecca Hardy, Celia Hartigan, Tricia Heaton, Christopher F. Higgins, Shirley Hodgson, Tessa Homfray, D. Horrigan, Catherine Houghton, Richard S. Houlston, Louise Hughes, Victoria Hunt, Lisa Irvine, Chris Jacobs, Steven James, Mattie R. James, Lisa Jeffers, Irene Jobson, Wanda K. Jones, Susan Kenwrick, Catherine Kightley, C W Kirk, Edwin P. Kirk, Emma Kivuva, Kelly Kohut, Monika Kosicka‐Slawinska, A. Kulkarni, N. Lambord, Craig B. Langman, Paul Leonard, S Levene, Sigurd Locker, Philip C. Logan, Mark Longmuir, Anneke Lucassen, V. Lyus, Alex Magee, Alison Male, Sahar Mansour, Deborah McBride, Emily P. McCann, Vivienne McConnell, Meriel McEntagart, C. McKeown, L. McLeish, Deborah McLeod, Andrew Melville, L J Mercer, Catherine Mercer, Anita Mitra, V Murday, Anne R. Murray, Kathryn Myhill, Jessica Myring, Emily A. O’Hara, Pauline Pearson, Gabriella Pichert, Kaye Platt, Carrie Pottinger, Sue Price, L. Protheroe, S. Pugh, Oliver Quarrell, Karen Randhawa, Caitlin Riddick, Lisa Robertson, A. Robinson, V. Roffey-Johnson, Mark Rogers, Stephen Rose, Sarah J. Rowe, Andrew Craig Schofield, Nazneen Rahman, Sibel Saya, Gillian Scott, Julia S. Scott, Angela Searle, Susan Shanley, S. Sharif, A. Shaw, Jacqui Shaw, J Shea-Simonds, Lucy Side, Julie Sillibourne, Kelly Claire Simon, Sarah Simpson, Susanna Slater, Susan V. Smalley, Katherine R. Smith, Lesley Snadden, Katie Snape, Judith Soloway, Y. Stait, Barbara Stayner, Mike Steel, Christopher Steel, Helen Stewart, D. Stirling, Mathew Thomas, Susan N. Thomas, Susannah Tomkins, Helen Turner, Anthony Vandersteen, Emma Wakeling, F. Waldrup, Catherine Watt, Sarah Watts, Andrea L. Webber, Catriona Whyte, Jennifer Wiggins, Ebony Williams, Laura Winchester, Helen Hanson, Clare Turnbull
17Citations signalées — pas une note de qualité
27Institutions déclarées
1Pays d’affiliation déclarés
Résumé fourni par la source
BACKGROUND: Breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. PATIENTS AND METHODS: We included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. ELIGIBILITY CRITERIA: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (<30 years), and (iv) concomitant ovarian cancer. We undertook exome sequencing of cases and carried out gene-level burden testing of rare damaging variants against those from 51 377 ethnicity-matched population controls from gnomAD. RESULTS: (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. CONCLUSIONS: This is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes
- Date Crossref
- 01/12/2022
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.
Institutions déclarées
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Sujets associés
BRCA gene mutations in cancerBreast Cancer Treatment StudiesPARP inhibition in cancer therapy