Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes
| العنوان: | Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes |
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| المؤلفون: | C. Loveday, A. Garrett, P. Law, S. Hanks, E. Poyastro-Pearson, J.W. Adlard, J. Barwell, J. Berg, A.F. Brady, C. Brewer, C. Chapman, J. Cook, R. Davidson, A. Donaldson, F. Douglas, L. Greenhalgh, A. Henderson, L. Izatt, A. Kumar, F. Lalloo, Z. Miedzybrodzka, P.J. Morrison, J. Paterson, M. Porteous, M.T. Rogers, L. Walker, D. Eccles, D.G. Evans, K. Snape, H. Hanson, R.S. Houlston, C. Turnbull, A. Ardern-Jones, J. Adlard, M. Ahmed, G. Attard, K. Bailey, E. Bancroft, C. Bardsley, D. Barton, M. Bartlett, L. Baxter, R. Belk, B. Bernhard, T. Bishop, L. Boyes, N. Bradshaw, S. Brant, G. Brice, G. Bromilow, C. Brooks, A. Bruce, B. Bulman, L. Burgess, J. Campbell, N. Canham, B. Castle, R. Cetnarskyj, O. Claber, N. Coates, T. Cole, A. Collins, S. Coulson, G. Crawford, D. Cruger, C. Cummings, L. D’Mello, L. Day, B. Dell, C. Dolling, H. Dorkins, S. Downing, S. Drummond, C. Dubras, J. Dunlop, S. Durrell, C. Eddy, M. Edwards, E. Edwards, J. Edwardson, R. Eeles, I. Ellis, F. Elmslie, G. Evans, B. Gibbons, C. Gardiner, N. Ghali, C. Giblin, S. Gibson, S. Goff, S. Goodman, D. Goudie, J. Grier, H. Gregory, S. Halliday, R. Hardy, C. Hartigan, T. Heaton, C. Higgins, S. Hodgson, T. Homfray, D. Horrigan, C. Houghton, L. Hughes, V. Hunt, L. Irvine, C. Jacobs, S. James, M. James, L. Jeffers, I. Jobson, W. Jones, M.J. Kennedy, S. Kenwrick, C. Kightley, C. Kirk, E. Kirk, E. Kivuva, K. Kohut, M. Kosicka-Slawinska, A. Kulkarni, N. Lambord, C. Langman, P. Leonard, S. Levene, S. Locker, P. Logan, M. Longmuir, A. Lucassen, V. Lyus, A. Magee, A. Male, S. Mansour, D. McBride, E. McCann, V. McConnell, M. McEntagart, C. McKeown, L. McLeish, D. McLeod, A. Melville, L. Mercer, C. Mercer, A. Mitra, V. Murday, A. Murray, K. Myhill, J. Myring, E. O'Hara, P. Pearson, G. Pichert, K. Platt, C. Pottinger, S. Price, L. Protheroe, S. Pugh, O. Quarrell, K. Randhawa, C. Riddick, L. Robertson, A. Robinson, V. Roffey-Johnson, M. Rogers, S. Rose, S. Rowe, A. Schofield, N. Rahman, S. Saya, G. Scott, J. Scott, A. Searle, S. Shanley, S. Sharif, A. Shaw, J. Shaw, J. Shea-Simonds, L. Side, J. Sillibourne, K. Simon, S. Simpson, S. Slater, S. Smalley, K. Smith, L. Snadden, J. Soloway, Y. Stait, B. Stayner, M. Steel, C. Steel, H. Stewart, D. Stirling, M. Thomas, S. Thomas, S. Tomkins, H. Turner, A. Vandersteen, E. Wakeling, F. Waldrup, C. Watt, S. Watts, A. Webber, C. Whyte, J. Wiggins, E. Williams, L. Winchester |
| المصدر: | Breast and Ovarian Cancer Susceptibility Collaboration, Loveday, C, Law, P, Hanks, S, Poyastro-Pearson, E, Adlard, J W, Barwell, J, Berg, J, Brady, A F, Donaldson, A, Douglas, F, Greenhalgh, L, Izatt, L, Lalloo, F, Miedzybrodzka, Z, Morrison, P J, Porteous, M, Eccles, D, Evans, D G, Snape, K, Houlston, R S, Hanson, H, Turnbull, C, Rogers, M T, Walker, L, Brewer, C, Paterson, J, Kumar, A, Davidson, R, Chapman, C & Cook, J 2022, ' Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes ', Annals of oncology : official journal of the European Society for Medical Oncology, vol. 33, no. 12, pp. 1318-1327 . https://doi.org/10.1016/j.annonc.2022.09.152Test Breast and Ovarian Cancer Susceptibility Collaboration, Loveday, C, Garrett, A, Law, P, Hanks, S, Poyastro-Pearson, E, Adlard, J W, Barwell, J, Berg, J, Brady, A F, 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, P J, Paterson, J, Porteous, M, Rogers, M T, Walker, L, Eccles, D, Evans, D G, Snape, K, Hanson, H, Houlston, R S & Turnbull, C 2022, ' Analysis of rare disruptive germline mutations in 2,135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes ', Annals of oncology : official journal of the European Society for Medical Oncology, vol. 33, no. 12, pp. 1318-1327 . https://doi.org/10.1016/j.annonc.2022.09.152Test |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Adult, Ovarian Neoplasms, rare-variant burden testing, Whole exome sequencing, Breast Neoplasms, Triple Negative Breast Neoplasms, Hematology, breast cancer, SDG 3 - Good Health and Well-being, Oncology, Humans, Female, Genetic Predisposition to Disease, cancer susceptibility genes, whole-exome sequencing, Rare variant burden testing, Germ-Line Mutation, Retrospective Studies, genetic susceptibility |
| الوصف: | 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 (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>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. |
| وصف الملف: | application/pdf; text |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6986764441617a144e724063e762ecfTest https://research.manchester.ac.uk/en/publications/2e088aaa-ff70-4a90-af9a-d3d781a5a2adTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d6986764441617a144e724063e762ecf |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |