Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes
| Title: | Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes |
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| Authors: | Loveday C; Garrett A; Law P; Hanks S; Poyastro-Pearson E; Adlard JW; Barwell J; Berg J; Brady AF; Brewer C; Chapman C; Cook J; Davidson R; Donaldson A; Douglas F; Greenhalgh L; Henderson A; Izatt L; Kumar A; Lalloo F; Miedzybrodzka Z; Morrison PJ; Paterson J; Porteous M; Rogers MT; Walker L; Ardern-Jones A; Adlard J; Ahmed M; Attard G; Bailey K; Bancroft E; Bardsley C; Barton D; Bartlett M; Baxter L; Belk R; Bernhard B; Bishop T; Boyes L; Bradshaw N; Brant S; Brice G; Bromilow G; Brooks C; Bruce A; Bulman B; Burgess L; Campbell J; Canham N; Castle B; Cetnarskyj R; Claber O; Coates N; Cole T; Collins A; Coulson S; Crawford G; Cruger D; Cummings C; D'Mello L; Day L; Dell B; Dolling C; Dorkins H; Downing S; Drummond S; Dubras C; Dunlop J; Durrell S; Eccles D; Eddy C; Edwards M; Edwards E; Edwardson J; Eeles R; Ellis I; Elmslie F; Evans G; Gibbons B; Gardiner C; Ghali N; Giblin C; Gibson S; Goff S; Goodman S; Goudie D; Grier J; Gregory H; Halliday S; Hardy R; Hartigan C; Heaton T; Higgins C; Hodgson S; Homfray T; Horrigan D; Houghton C; Houlston RS; Hughes L; Hunt V; Irvine L; Jacobs C; James S; James M; Jeffers L; Jobson I; Jones W; Kennedy MJ; Kenwrick S; Kightley C; Kirk C; Kirk E; Kivuva E; Kohut K; Kosicka-Slawinska M; Kulkarni A; Lambord N; Langman C; Leonard P; Levene S; Locker S; Logan P; Longmuir M; Lucassen A; Lyus V; Magee A; Male A; Mansour S; McBride D; McCann E; McConnell V; McEntagart M; McKeown C; McLeish L; McLeod D; Melville A; Mercer L; Mercer C; Mitra A; Murday V; Murray A; Myhill K; Myring J; O'Hara E; Pearson P; Pichert G; Platt K; Pottinger C; Price S; Protheroe L; Pugh S; Quarrell O; Randhawa K; Riddick C; Robertson L; Robinson A; Roffey-Johnson V; Rogers M; Rose S; Rowe S; Schofield A; Rahman N; Saya S; Scott G; Scott J; Searle A; Shanley S; Sharif S; Shaw A; Shaw J; Shea-Simonds J; Side L; Sillibourne J; Simon K; Simpson S; Slater S; Smalley S; Smith K; Snadden L; Snape K; Soloway J; Stait Y; Stayner B; Steel M; Steel C; Stewart H; Stirling D; Thomas M; Thomas S; Tomkins S; Turner H; Vandersteen A; Wakeling E; Waldrup F; Watt C; Watts S; Webber A; Whyte C; Wiggins J; Williams E; Winchester L; Evans DG; Hanson H; Turnbull C |
| Source: | Annals of Oncology, 2022 |
| Publisher Information: | Elsevier BV |
| Publication Year: | 2022 |
| Collection: | Newcastle University Library ePrints Service |
| Description: | © 2022 The Author(s). 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 (80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10−5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10−4 (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. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | unknown |
| Relation: | https://eprints.ncl.ac.uk/287775; https://eprints.ncl.ac.uk/fulltext.aspx?url=287775/56BFCA7D-86EE-447C-9638-F608A821BD4B.pdf&pub_id=287775 |
| Availability: | https://eprints.ncl.ac.uk/287775 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.CEB9E9D0 |
| Database: | BASE |