Breast cancer risks associated with missense variants in breast cancer susceptibility genes
| العنوان: | Breast cancer risks associated with missense variants in breast cancer susceptibility genes |
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| المؤلفون: | Dorling, L., Carvalho, S., Allen, J., Parsons, M.T., Fortuno, C., Gonzalez-Neira, A., Heijl, S.M., Adank, M.A., Ahearn, T.U., Andrulis, I.L., Auvinen, P., Becher, H., Beckmann, M.W., Behrens, S., Bermisheva, M., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bremer, M., Briceno, I., Camp, N.J., Campbell, A., Castelao, J.E., Chang-Claude, J., Chanock, S.J., Chenevix-Trench, G., Collee, J.M., Czene, K., Dennis, J., Dork, T., Eriksson, M., Evans, D.G., Fasching, P.A., Figueroa, J., Flyger, H., Gabrielson, M., Gago-Dominguez, M., Garcia-Closas, M., Giles, G.G., Glendon, G., Guenel, P., Gundert, M., Hadjisavvas, A., Hahnen, E., Hall, P., Hamann, U., Harkness, E.F., Hartman, M., Hogervorst, F.B.L., Hollestelle, A., Hoppe, R., Howell, A., Jakubowska, A., Jung, A., Khusnutdinova, E., Kim, S.W., Ko, Y.D., Kristensen, V.N., Lakeman, I.M.M., Li, J.M., Lindblom, A., Loizidou, M.A., Lophatananon, A., Lubinski, J., Luccarini, C., Madsen, M.J., Mannermaa, A., Manoochehri, M., Margolin, S., Mavroudis, D., Milne, R.L., Taib, N.A.M., Muir, K., Nevanlinna, H., Newman, W.G., Oosterwijk, J.C., Park, S.K., Peterlongo, P., Radice, P., Saloustros, E., Sawyer, E.J., Schmutzler, R.K., Shah, M.T., Sim, X., Southey, M.C., Surowy, H., Suvanto, M., Tomlinson, I., Torres, D., Truong, T., Asperen, C.J. van, Waltes, R., Wang, Q., Yang, X.H.R., Pharoah, P.D.P., Schmidt, M.K., Benitez, J., Vroling, B., Dunning, A.M., Teo, S.H., Kvist, A., Hoya, M. de la, Devilee, P., Spurdle, A.B., Vreeswijk, M.P.G., Easton, D.F., NBCS Collaborators, KConFab Investigators, SGBCC Investigators |
| المساهمون: | Clinical Genetics, Medical Oncology, Apollo - University of Cambridge Repository, Dennis, Joe [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), University of Helsinki, Clinicum, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Wellcome Trust, WT: 633784, v203477/Z/16/Z, Horizon 2020 Framework Programme, H2020, Cancer Research UK, CRUK: C1287/A16563, The sequencing and analysis for this project was funded by the European Union’s Horizon 2020 Research and Innovation Programme (BRIDGES: grant number 634935) and the Wellcome Trust [grant no: v203477/Z/16/Z]. BCAC co-ordination was additionally funded by the European Union’s Horizon 2020 Research and Innovation Programme (BRIDGES: grant number 634935, BCAST: grant number 633784) and by Cancer Research UK [C1287/A16563]. Study specific funding is given in the Additional Note., HAL UVSQ, Équipe |
| المصدر: | Genome Medicine, 14(1). BMC Genome Medicine, 14(1):51. BioMed Central Ltd. Dorling, L, Carvalho, S, Allen, J, Parsons, M T, Fortuno, C, González-Neira, A, Heijl, S M, Adank, M A, Ahearn, T U, Andrulis, I L, Auvinen, P, Becher, H, Beckmann, M W, Behrens, S, Bermisheva, M, Bogdanova, N V, Bojesen, S E, Bolla, M K, Bremer, M, Briceno, I, Camp, N J, Campbell, A, Castelao, J E, Chang-Claude, J, Chanock, S J, Chenevix-Trench, G, Collée, J M, Czene, K, Dennis, J, Dörk, T, Eriksson, M, Evans, D G, Fasching, P A, Figueroa, J, Flyger, H, Gabrielson, M, Gago-Dominguez, M, García-Closas, M, Giles, G G, Glendon, G, Guénel, P, Gündert, M, Hadjisavvas, A, Hahnen, E, Hall, P, Hamann, U, Harkness, E F, Hartman, M, Hogervorst, F B L, Hollestelle, A, Hoppe, R, Howell, A, Jakubowska, A, Jung, A, Khusnutdinova, E, Kim, S-W, Ko, Y-D, Kristensen, V N, Lakeman, I M M, Li, J, Lindblom, A, Loizidou, M A, Lophatananon, A, Lubiński, J, Luccarini, C, Madsen, M J, Mannermaa, A, Manoochehri, M, Margolin, S, Mavroudis, D, Milne, R L, Taib, N A M, Muir, K, Nevanlinna, H, Newman, W G, Oosterwijk, J C, Park, S K, Peterlongo, P, Radice, P, Saloustros, E, Sawyer, E J, Schmutzler, R K, Shah, M, Sim, X, Southey, M C, Surowy, H, Suvanto, M, Tomlinson, I, Torres, D, Truong, T, van Asperen, C J, Waltes, R, Wang, Q, Yang, X R, Pharoah, P D P, Schmidt, M K, Benitez, J, Vroling, B, Dunning, A M, Teo, S H, Kvist, A, de la Hoya, M, Devilee, P, Spurdle, A B, Vreeswijk, M P G & Easton, D F 2022, ' Breast cancer risks associated with missense variants in breast cancer susceptibility genes ', Genome Medicine, vol. 14, 51 . https://doi.org/10.1186/s13073-022-01052-8Test Genome Med. 14:51 (2022) Genome medicine, 14:51. BMC 2022, ' Breast cancer risks associated with missense variants in breast cancer susceptibility genes ', Genome Medicine, vol. 14, no. 1, 51, pp. 51 . https://doi.org/10.1186/s13073-022-01052-8Test Genome Medicine Genome Medicine, 2022, 14 (1), pp.51. ⟨10.1186/s13073-022-01052-8⟩ |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mutation, Missense, Breast Neoplasms, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Breast Neoplasms/genetics, Breast Cancer, Genetic Epidemiology, Missense Variants, Risk Prediction, CLASSIFICATION, Breast cancer, Missense variants, SDG 3 - Good Health and Well-being, 3123 Gynaecology and paediatrics, SEQUENCE VARIANTS, Genetics, Humans, Genetic Predisposition to Disease, Genetic epidemiology, ddc:610, skin and connective tissue diseases, Molecular Biology, Genetics (clinical), MUTATIONS, Research, UNKNOWN CLINICAL-SIGNIFICANCE, 1184 Genetics, developmental biology, physiology, FRAMEWORK, BRCA1, Risk prediction, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, SUBSTITUTIONS, Case-Control Studies, Mutation, Molecular Medicine, Female, Missense, PATHOGENICITY |
| الوصف: | Background Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility. |
| وصف الملف: | application/pdf; text/xml; application/zip |
| اللغة: | English |
| تدمد: | 1756-994X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6c185147962665a775ec9e902da9f70Test http://hdl.handle.net/1887/3563684Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e6c185147962665a775ec9e902da9f70 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1756994X |
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