499 results on '"Balmaña, J"'
Search Results
2. Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer
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Harvey-Jones, E., Raghunandan, M., Robbez-Masson, L., Magraner-Pardo, L., Alaguthurai, T., Yablonovitch, A., Yen, J., Xiao, H., Brough, R., Frankum, J., Song, F., Yeung, J., Savy, T., Gulati, A., Alexander, J., Kemp, H., Starling, C., Konde, A., Marlow, R., Cheang, M., Proszek, P., Hubank, M., Cai, M., Trendell, J., Lu, R., Liccardo, R., Ravindran, N., Llop-Guevara, A., Rodriguez, O., Balmana, J., Lukashchuk, N., Dorschner, M., Drusbosky, L., Roxanis, I., Serra, V., Haider, S., Pettitt, S.J., Lord, C.J., and Tutt, A.N.J.
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- 2024
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3. Population-based germline breast cancer gene association studies and meta-analysis to inform wider mainstream testing
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Rowlands, C.F., Allen, S., Balmaña, J., Domchek, S.M., Evans, D.G., Hanson, H., Hoogerbrugge, N., James, P.A., Nathanson, K.L., Robson, M., Tischkowitz, M., Foulkes, W.D., and Turnbull, C.
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- 2024
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4. Post-hematopoietic stem cell transplant squamous cell carcinoma in patients with Fanconi anemia: a dreadful enemy
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Murillo-Sanjuán, L., Balmaña, J., de Pablo García-Cuenca, A., Lorente Guerrero, J., Uria Oficialdegui, M. L., Carrasco, E., and Diaz-de-Heredia, C.
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- 2022
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5. Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer
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Condorelli, M., Bruzzone, M., Ceppi, M., Ferrari, A., Grinshpun, A., Hamy, A.S., de Azambuja, E., Carrasco, E., Peccatori, F.A., Di Meglio, A., Paluch-Shimon, S., Poorvu, P.D., Venturelli, M., Rousset-Jablonski, C., Senechal, C., Livraghi, L., Ponzone, R., De Marchis, L., Pogoda, K., Sonnenblick, A., Villarreal-Garza, C., Córdoba, O., Teixeira, L., Clatot, F., Punie, K., Graffeo, R., Dieci, M.V., Pérez-Fidalgo, J.A., Duhoux, F.P., Puglisi, F., Ferreira, A.R., Blondeaux, E., Peretz-Yablonski, T., Caron, O., Saule, C., Ameye, L., Balmaña, J., Partridge, A.H., Azim, H.A., Demeestere, I., and Lambertini, M.
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- 2021
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6. Olaparib monotherapy as primary treatment in unselected triple negative breast cancer
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Eikesdal, H.P., Yndestad, S., Elzawahry, A., Llop-Guevara, A., Gilje, B., Blix, E.S., Espelid, H., Lundgren, S., Geisler, J., Vagstad, G., Venizelos, A., Minsaas, L., Leirvaag, B., Gudlaugsson, E.G., Vintermyr, O.K., Aase, H.S., Aas, T., Balmaña, J., Serra, V., Janssen, E.A.M., Knappskog, S., and Lønning, P.E.
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- 2021
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7. Population-based germline breast cancer gene association studies and meta-analysis to inform wider mainstream testing.
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Rowlands, CF, Allen, S, Balmaña, J, Domchek, SM, Evans, DG, Hanson, H, Hoogerbrugge, N, James, PA, Nathanson, KL, Robson, M, Tischkowitz, M, Foulkes, WD, Turnbull, C, Rowlands, CF, Allen, S, Balmaña, J, Domchek, SM, Evans, DG, Hanson, H, Hoogerbrugge, N, James, PA, Nathanson, KL, Robson, M, Tischkowitz, M, Foulkes, WD, and Turnbull, C
- Abstract
BACKGROUND: Germline genetic testing, previously restricted to familial and young-onset breast cancer, is now offered increasingly broadly to patients with 'population-type' breast cancer in mainstream oncology clinics, with wide variation in the genes included. PATIENTS AND METHODS: Weighted meta-analysis was carried out for three population-based case-control studies (BRIDGES, CARRIERS and UK Biobank) comprising in total 101 397 women with breast cancer and 312 944 women without breast cancer, to quantify 37 putative breast cancer susceptibility genes (BCSGs) for the frequency of pathogenic variants (PVs) in unselected, 'population-type' breast cancer cases and their association with breast cancer and its subtypes. RESULTS: Meta-analysed odds ratios (ORs) and frequencies of PVs in 'population-type' breast cancer cases were generated for BRCA1 (OR 8.73, 95% confidence interval (CI) 7.47-10.20; 1 in 101), BRCA2 (OR 5.68, 95% CI 5.13-6.30; 1 in 68) and PALB2 (OR 4.30, 95% CI 3.68-5.03; 1 in 187). For both CHEK2 (OR 2.40, 95% CI 2.21-2.62; 1 in 73) and ATM (OR 2.16, 95% CI 1.93-2.41; 1 in 132) subgroup analysis showed a stronger association with oestrogen receptor-positive disease. The magnitude of association and frequency of PVs were low for RAD51C (OR 1.53, 95% CI 1.29-2.04; 1 in 913), RAD51D (OR 1.76, 95% CI 1.29-2.41; 1 in 1079) and BARD1 (OR 2.34, 95% CI 1.85-2.97; 1 in 672); frequencies and associations were higher when the analysis was restricted to triple-negative breast cancers. The PV frequency in 'population-type' breast cancer cases was very low for 'syndromic' BCSGs TP53 (1 in 1844), STK11 (1 in 11 525), CDH1 (1 in 2668), PTEN (1 in 3755) and NF1 (1 in 1470), with metrics of association also modest ranging from OR 3.62 (95% CI 1.98-6.61) for TP53 down to OR 1.60 (95% CI 0.48-5.30) for STK11. CONCLUSIONS: These metrics reflecting 'population-type' breast cancer will be informative in defining the appropriate gene set as we continue to expand to germline t
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- 2024
8. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†
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Stjepanovic, N., Moreira, L., Carneiro, F., Balaguer, F., Cervantes, A., Balmaña, J., and Martinelli, E.
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- 2019
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9. A decade of clinical development of PARP inhibitors in perspective
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Mateo, J., Lord, C.J., Serra, V., Tutt, A., Balmaña, J., Castroviejo-Bermejo, M., Cruz, C., Oaknin, A., Kaye, S.B., and de Bono, J.S.
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- 2019
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10. A narrative overview of the patients’ outcomes after multigene cancer panel testing, and a thorough evaluation of its implications for genetic counselling
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Esteban, I., Lopez-Fernandez, A., and Balmaña, J.
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- 2019
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11. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer
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Cruz, C., Castroviejo-Bermejo, M., Gutiérrez-Enríquez, S., Llop-Guevara, A., Ibrahim, Y.H., Gris-Oliver, A., Bonache, S., Morancho, B., Bruna, A., Rueda, O.M., Lai, Z., Polanska, U.M., Jones, G.N., Kristel, P., de Bustos, L., Guzman, M., Rodríguez, O., Grueso, J., Montalban, G., Caratú, G., Mancuso, F., Fasani, R., Jiménez, J., Howat, W.J., Dougherty, B., Vivancos, A., Nuciforo, P., Serres-Créixams, X., Rubio, I.T., Oaknin, A., Cadogan, E., Barrett, J.C., Caldas, C., Baselga, J., Saura, C., Cortés, J., Arribas, J., Jonkers, J., Díez, O., O’Connor, M.J., Balmaña, J., and Serra, V.
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- 2018
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12. 203P Clinical effectiveness of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer (mBC) by ER expression level: Subgroup analysis from phase IIIb LUCY trial
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Gelmon, K.A., primary, Fasching, P.A., additional, Delaloge, S., additional, Park, Y.H., additional, Eisen, A.F., additional, Bourgeois, H., additional, Kemp, Z., additional, Jankowski, T., additional, Sohn, J., additional, Aksoy, S., additional, Timcheva, C.V., additional, Park-Simon, T-W., additional, Torres, A. Anton, additional, John, E., additional, Gibson, I., additional, Lukashchuk, N., additional, Baria, K., additional, and Balmaña, J., additional
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- 2023
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13. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO Clinical Practice Guideline
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Sessa, C., primary, Balmaña, J., additional, Bober, S.L., additional, Cardoso, M.J., additional, Colombo, N., additional, Curigliano, G., additional, Domchek, S.M., additional, Evans, D.G., additional, Fischerova, D., additional, Harbeck, N., additional, Kuhl, C., additional, Lemley, B., additional, Levy-Lahad, E., additional, Lambertini, M., additional, Ledermann, J.A., additional, Loibl, S., additional, Phillips, K.-A., additional, and Paluch-Shimon, S., additional
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- 2023
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14. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO Clinical Practice Guideline
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Sessa, C., Balmaña, J., Bober, S. L., Cardoso, Maria-Joao, Colombo, N., Curigliano, G., Domchek, S. M., Evans, D. G., Fischerova, D., Harbeck, N., Kuhl, C., Lemley, B., Levy-Lahad, E., Lambertini, M., Ledermann, J. A., Loibl, S., Phillips, K.-A., Paluch-Shimon, S., Repositório da Universidade de Lisboa, Sessa, C, Balmana, J, Bober, S, Cardoso, M, Colombo, N, Curigliano, G, Domchek, S, Evans, D, Fischerova, D, Harbeck, N, Kuhl, C, Lemley, B, Levy-Lahad, E, Lambertini, M, Ledermann, J, Loibl, S, Phillips, K, and Paluch-Shimon, S
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hereditary breast and ovarian cancer syndrome ,Oncology ,ESMO Clinical Practice Guideline ,Hereditary breast and ovarian cancer syndromes ,BRCA ,Risk reduction ,Hematology - Abstract
© 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved
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- 2023
15. Risk factors of complications after nipple-sparing mastectomies in women with breast cancer risk gene mutations (BRCA1, BRCA2, PALB2)
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De La Torre-Fernandez De Vega, J., primary, Valles, E., additional, Barberan, L., additional, Pancorbo, M., additional, Comas, M.D.M., additional, Garrido, A., additional, Hernan, I., additional, Vives, I., additional, Rivero, J., additional, Morales, C., additional, Siso, C., additional, Cruella, M., additional, Balmaña, J., additional, Gil-Moreno, A., additional, and Espinosa Bravo, M., additional
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- 2022
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16. 146P HRD/TIL-low high-risk breast cancer is characterized by good prognosis (the RADIMMUNE trial)
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Pellegrino, B., primary, Llop-Guevara, A., additional, Solinas, C., additional, Campanini, N., additional, Tommasi, C., additional, Michiara, M., additional, Boggiani, D., additional, Sikokis, A., additional, Frassoldati, A., additional, Casarini, C., additional, Cretella, E., additional, Zoppoli, G., additional, Lambertini, M., additional, Dieci, M.V., additional, Cortesi, L., additional, Silini, E., additional, Balmaña, J., additional, Willard-Gallo, K., additional, Serra, V., additional, and Musolino, A., additional
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- 2022
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17. EP07.01-023 Family History of Cancer in a Series of Malignant Pleural Mesothelioma (MPM) Patients (P)
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Cedres, S., primary, Cruellas, M., additional, Assaf, J.D., additional, Iranzo, P., additional, Callejo, A., additional, Pardo, N., additional, Navarro, A., additional, Martinez-Marti, A., additional, Carbonell, C., additional, Frigola, J., additional, Amat, R., additional, Gonzalo, J., additional, Navarro, V., additional, Dienstmann, R., additional, Balmaña, J., additional, and Felip, E., additional
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- 2022
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18. 262P Niraparib plus aromatase inhibitors (AI) for germinal mutated BRCA1/2 (gBRCAm) or homologous recombination-deficient (HRd), hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC): LUZERN interim analysis
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Pimentel, I., primary, Lema Roso, L., additional, Ramos Vazquez, M., additional, García Saenz, J.Á., additional, Palacios-Ozores, P., additional, De la Haba Rodriguez, J., additional, Blanch, S., additional, Prat, A., additional, Ales Martínez, J.E., additional, Alba Conejo, E., additional, Balmaña, J., additional, Perez Garcia, J.M., additional, Sampayo-Cordero, M., additional, Malfettone, A., additional, Cortés, J., additional, and Llombart Cussac, A., additional
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- 2022
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19. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors
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Balmaña, J., Tung, N.M., Isakoff, S.J., Graña, B., Ryan, P.D., Saura, C., Lowe, E.S., Frewer, P., Winer, E., Baselga, J., and Garber, J.E.
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- 2014
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20. 405P HRD biomarkers in blood samples from BRCA1/BRCA2-associated advanced breast cancer (BC) patients (pts)
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Serra, V., Domenech, H., Pettitt, S.J., Proszek, P., Pedretti, F., Ropero, A. Herencia, Hernandez, A. Rodriguez, Suñol, A., Viaplana, C., Vivo, J. Domenech, Gutierrez-Enriquez, S., Oliveira, M., Mateo, J., Prat, A., Lord, C.J., Tutt, A.N.J., Llop-Guevara, A., and Balmaña, J.
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- 2024
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21. 266P Association of RAD51 and efficacy outcomes in patients with HER2-negative breast cancer (BC) and homologous recombination deficiency (HRD): Post-hoc analysis of the GeparOla trial
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Villacampa, G., Filmann, N., Fasching, P.A., Balmaña, J., Karn, T., Marmé, F., Klare, P., Mueller, V., Schem, C., Fehm, T.N., Stickeler, E., Van Mackelenbergh, M., Felder, B., Nekljudova, V., Llop-Guevara, A., Denkert, C., Loibl, S., and Serra, V.
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- 2024
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22. 18P The role of CTNNA1 truncating variants in hereditary diffuse gastric cancer (HDGC)
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Lobo, S., Dias, A., Ferreira, M., Herrera-Mullar, J., Svrcek, M., Hueneburg, R., Moreira, L., Tinschert, S., Boussemart, L., Balmaña, J., Strong, V., Lazaro, C., Katona, B., Colas, C., Coulet, F., Karam, R., Pereira, P.S., Benusiglio, P.R., and Oliveira, C.
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- 2024
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23. 1815O Breastfeeding after breast cancer in young BRCA carriers: Results from an international cohort study
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Blondeaux, E., Delucchi, V., Mariamidze, E., Bernstein Molho, R., Hamy-Petit, A-S., Ferrari, A., Linn, S., Kim, H.J., Agostinetto, E., Paluch-Shimon, S., Toss, A., Di Meglio, A., Balmaña, J., Yerushalmi, R., Rodriguez-Wallberg, K.R., Demeestere, I., Azim, H.A., Jr., Peccatori, F.A., Partridge, A.H., and Lambertini, M.
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- 2024
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24. Germline BRCA testing is moving from cancer risk assessment to a predictive biomarker for targeting cancer therapeutics
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Moreno, L., Linossi, C., Esteban, I., Gadea, N., Carrasco, E., Bonache, S., Gutiérrez-Enríquez, S., Cruz, C., Díez, O., and Balmaña, J.
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- 2016
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25. SEOM clinical guidelines in Hereditary Breast and ovarian cancer
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Llort, G., Chirivella, I., Morales, R., Serrano, R., Sanchez, A. Beatriz, Teulé, A., Lastra, E., Brunet, J., Balmaña, J., Graña, B., and On behalf of the SEOM Hereditary Cancer Working Group
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- 2015
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26. Consenso en cáncer hereditario entre la Sociedad Española de Oncología Médica y las sociedades de atención primaria
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Robles, L., Balmaña, J., Barrel, I., Grandes, S., Graña, B., Guillén, C., Marcos, H., Ramírez, D., Redondo, E., and Sánchez, J.
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- 2013
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27. Polygenic risk modeling for prediction of epithelial ovarian cancer risk
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Dareng, EO, Tyrer, JP, Barnes, DR, Jones, MR, Yang, X, Aben, KKH, Adank, MA, Agata, S, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Aravantinos, G, Arun, BK, Augustinsson, A, Balmaña, J, Bandera, EV, Barkardottir, RB, Barrowdale, D, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Bjorge, L, Black, A, Bogdanova, NV, Bonanni, B, Borg, A, Brenton, JD, Budzilowska, A, Butzow, R, Buys, SS, Cai, H, Caligo, MA, Campbell, I, Cannioto, R, Cassingham, H, Chang-Claude, J, Chanock, SJ, Chen, K, Chiew, YE, Chung, WK, Claes, KBM, Colonna, S, Cook, LS, Couch, FJ, Daly, MB, Dao, F, Davies, E, De La Hoya, M, De Putter, R, Dennis, J, DePersia, A, Devilee, P, Diez, O, Ding, YC, Doherty, JA, Domchek, SM, Dörk, T, Du Bois, A, Dürst, M, Eccles, DM, Eliassen, HA, Engel, C, Evans, GD, Fasching, PA, Flanagan, JM, Fortner, RT, Machackova, E, Friedman, E, Ganz, PA, Garber, J, Gensini, F, Giles, GG, Glendon, G, Godwin, AK, Goodman, MT, Greene, MH, Gronwald, J, Hahnen, E, Haiman, CA, Håkansson, N, Hamann, U, Hansen, TVO, Harris, HR, Hartman, M, Heitz, F, Hildebrandt, MAT, Høgdall, E, Høgdall, CK, Hopper, JL, Huang, RY, Huff, C, Hulick, PJ, Huntsman, DG, Imyanitov, EN, Van Der Hout, AH, Isaacs, C, Jakubowska, A, James, PA, Dareng, EO [0000-0003-0802-419X], Tyrer, JP [0000-0003-3724-4757], Barnes, DR [0000-0002-3781-7570], Yang, X [0000-0003-0037-3790], Andrulis, IL [0000-0002-4226-6435], Augustinsson, A [0000-0003-3415-0536], Barrowdale, D [0000-0003-1661-3939], Bonanni, B [0000-0003-3589-2128], Brenton, JD [0000-0002-5738-6683], Butzow, R [0000-0003-4366-5099], Chanock, SJ [0000-0002-2324-3393], Claes, KBM [0000-0003-0841-7372], de la Hoya, M [0000-0002-8113-1410], de Putter, R [0000-0001-9410-8941], Dennis, J [0000-0003-4591-1214], Devilee, P [0000-0002-8023-2009], du Bois, A [0000-0002-8477-506X], Machackova, E [0000-0002-0246-1471], Giles, GG [0000-0003-4946-9099], Godwin, AK [0000-0002-3987-9580], Greene, MH [0000-0003-1852-9239], Heitz, F [0000-0002-2412-0352], Hulick, PJ [0000-0001-8397-4078], Jakubowska, A [0000-0002-5650-0501], James, PA [0000-0002-4361-4657], and Apollo - University of Cambridge Repository
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Rare Diseases ,FOS: Biological sciences ,Prevention ,Genetics ,32 Biomedical and Clinical Sciences ,3211 Oncology and Carcinogenesis ,3105 Genetics ,31 Biological Sciences ,Ovarian Cancer ,Cancer - Abstract
Funder: Funding details are provided in the Supplementary Material, Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28–1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08–1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30–1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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- 2022
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28. Polygenic risk modeling for prediction of epithelial ovarian cancer risk
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Dareng, E.O., Tyrer, J.P., Barnes, D.R., Jones, M.R., Yang, X, Aben, K.K.H., Adank, M.A., Agata, S., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Aravantinos, G., Arun, B.K., Augustinsson, A., Balmaña, J., Bandera, E.V., Barkardottir, R.B., Barrowdale, D., Beckmann, M.W., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Bernardini, M.Q., Bjorge, L., Black, A., Bogdanova, N.V., Bonanni, B., Borg, A., Brenton, J.D., Budzilowska, A., Butzow, R., Buys, S.S., Cai, H., Caligo, M.A., Campbell, I., Cannioto, R., Cassingham, H., Chang-Claude, J., Chanock, S.J., Chen, K., Chiew, Y.E., Chung, W.K., Claes, K.B.M., Colonna, S., Cook, L.S., Couch, F.J., Daly, M.B., Dao, F., Davies, E., Hoya, M. de la, Putter, R. de, Dennis, J., DePersia, A., Devilee, P., Diez, O., Ding, Y.C., Doherty, J.A., Domchek, S.M., Dörk, T., Bois, A. du, Dürst, M., Eccles, D.M., Eliassen, H.A., Engel, C., Evans, G.D., Fasching, P.A., Flanagan, J.M., Fortner, R.T., Machackova, E., Friedman, E., Ganz, P.A., Garber, J., Gensini, F., Giles, G.G., Glendon, G., Godwin, A.K., Goodman, M.T., Greene, M.H., Gronwald, J., Hahnen, E., Haiman, C.A., Håkansson, N., Hamann, U., Hansen, T.V., Harris, H.R., Hartman, M, Heitz, F., Hildebrandt, M.A., Høgdall, E., Høgdall, C.K., Hopper, J.L., Huang, R.Y., Huff, C., Hulick, P.J., Huntsman, D.G., Imyanitov, E.N., Isaacs, C., Jakubowska, A., James, P.A., Kiemeney, L.A.L.M., Altena, A.M. van, Janavicius, R., Antoniou, A.C., Pharoah, P.D., Dareng, E.O., Tyrer, J.P., Barnes, D.R., Jones, M.R., Yang, X, Aben, K.K.H., Adank, M.A., Agata, S., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Aravantinos, G., Arun, B.K., Augustinsson, A., Balmaña, J., Bandera, E.V., Barkardottir, R.B., Barrowdale, D., Beckmann, M.W., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Bernardini, M.Q., Bjorge, L., Black, A., Bogdanova, N.V., Bonanni, B., Borg, A., Brenton, J.D., Budzilowska, A., Butzow, R., Buys, S.S., Cai, H., Caligo, M.A., Campbell, I., Cannioto, R., Cassingham, H., Chang-Claude, J., Chanock, S.J., Chen, K., Chiew, Y.E., Chung, W.K., Claes, K.B.M., Colonna, S., Cook, L.S., Couch, F.J., Daly, M.B., Dao, F., Davies, E., Hoya, M. de la, Putter, R. de, Dennis, J., DePersia, A., Devilee, P., Diez, O., Ding, Y.C., Doherty, J.A., Domchek, S.M., Dörk, T., Bois, A. du, Dürst, M., Eccles, D.M., Eliassen, H.A., Engel, C., Evans, G.D., Fasching, P.A., Flanagan, J.M., Fortner, R.T., Machackova, E., Friedman, E., Ganz, P.A., Garber, J., Gensini, F., Giles, G.G., Glendon, G., Godwin, A.K., Goodman, M.T., Greene, M.H., Gronwald, J., Hahnen, E., Haiman, C.A., Håkansson, N., Hamann, U., Hansen, T.V., Harris, H.R., Hartman, M, Heitz, F., Hildebrandt, M.A., Høgdall, E., Høgdall, C.K., Hopper, J.L., Huang, R.Y., Huff, C., Hulick, P.J., Huntsman, D.G., Imyanitov, E.N., Isaacs, C., Jakubowska, A., James, P.A., Kiemeney, L.A.L.M., Altena, A.M. van, Janavicius, R., Antoniou, A.C., and Pharoah, P.D.
- Abstract
Item does not contain fulltext, Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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- 2022
29. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
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Schmoll, H.J., Van Cutsem, E., Stein, A., Valentini, V., Glimelius, B., Haustermans, K., Nordlinger, B., van de Velde, C.J., Balmana, J., Regula, J., Nagtegaal, I.D., Beets-Tan, R.G., Arnold, D., Ciardiello, F., Hoff, P., Kerr, D., Köhne, C.H., Labianca, R., Price, T., Scheithauer, W., Sobrero, A., Tabernero, J., Aderka, D., Barroso, S., Bodoky, G., Douillard, J.Y., El Ghazaly, H., Gallardo, J., Garin, A., Glynne-Jones, R., Jordan, K., Meshcheryakov, A., Papamichail, D., Pfeiffer, P., Souglakos, I., Turhal, S., and Cervantes, A.
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- 2012
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30. 139P Breast cancer risk estimation (CanRisk tool) and perception in unaffected women with family history of breast cancer
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Ramon y Cajal, T., primary, Lopez-Fernandez, À., additional, Pardo, M., additional, Darder, E., additional, Perez, E., additional, Costal, A., additional, Teule, A., additional, Perez, A., additional, Torres, M., additional, Alfonso, R., additional, Vallmajó, A., additional, Tuset Der-Abrain, N., additional, Cruellas Lapena, M., additional, Espinosa-Bravo, M., additional, Diez, O., additional, Lázaro, C., additional, Feliubadaló, L., additional, Llort Pursals, G., additional, Brunet Vidal, J.M., additional, and Balmaña, J., additional
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- 2022
- Full Text
- View/download PDF
31. 12P Prevalence of functional and genomic homologous recombination deficiency (HRD) in germline RAD51C/D patients
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Llop-Guevara, A., primary, Torres-Esquius, S., additional, Romey, M., additional, Gutierrez-Enriquez, S., additional, Nuciforo, P.G., additional, Diez, O., additional, Llort Pursals, G., additional, Teule, A., additional, Vallmajó, A., additional, Diaz De Corcuera, I., additional, Chirivella Gonzalez, I., additional, Gonzalez Santiago, S., additional, Sanchez Henarejos, P., additional, Sanz Buxo, J., additional, Guillen Ponce, C., additional, Sanchez, A.B., additional, Brunet Vidal, J.M., additional, Denkert, C., additional, Serra Elizalde, V., additional, and Balmaña, J., additional
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- 2022
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32. BRCA in breast cancer: ESMO Clinical Practice Guidelines
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Balmaña, J., Díez, O., Rubio, I.T., and Cardoso, F.
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- 2011
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33. Association of RAD51 with homologous recombination deficiency (HRD) and clinical outcomes in untreated triple-negative breast cancer (TNBC): analysis of the GeparSixto randomized clinical trial
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Llop-Guevara, A., primary, Loibl, S., additional, Villacampa, G., additional, Vladimirova, V., additional, Schneeweiss, A., additional, Karn, T., additional, Zahm, D.-M., additional, Herencia-Ropero, A., additional, Jank, P., additional, van Mackelenbergh, M., additional, Fasching, P.A., additional, Marmé, F., additional, Stickeler, E., additional, Schem, C., additional, Dienstmann, R., additional, Florian, S., additional, Nekljudova, V., additional, Balmaña, J., additional, Hahnen, E., additional, Denkert, C., additional, and Serra, V., additional
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- 2021
- Full Text
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34. Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC)
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Andrés, R., Pajares, I., Balmaña, J., Llort, G., Ramón y Cajal, T., Chirivella, I., Aguirre, E., Robles, L., Lastra, E., Pérez-Segura, P., Bosch, N., Yagüe, C., Lerma, E., Godino, J., Miramar, M. D., Moros, M., Astier, P., Saez, B., Vidal, M. J., Arcusa, A., Ramón y Cajal, S., Calvo, M. T., and Tres, A.
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- 2014
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35. Familial colorectal cancer risk: ESMO Clinical Practice Guidelines
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Balmaña, J., Castells, A., and Cervantes, A.
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- 2010
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36. BRCA in breast cancer: ESMO Clinical Practice Guidelines
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Balmaña, J., Diez, O., Rubio, I., and Castiglione, M.
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- 2010
- Full Text
- View/download PDF
37. Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a Lynch syndrome family with conserved MLH1 expression tumors
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Pineda, M., González-Acosta, M., Thompson, B. A., Sánchez, R., Gómez, C., Martínez-López, J., Perea, J., Caldés, T., Rodríguez, Y., Landolfi, S., Balmaña, J., Lázaro, C., Robles, L., Capellá, G., and Rueda, D.
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- 2015
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- View/download PDF
38. Post-hematopoietic stem cell transplant squamous cell carcinoma in patients with Fanconi anemia: a dreadful enemy
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Murillo-Sanjuán, L., primary, Balmaña, J., additional, de Pablo García-Cuenca, A., additional, Lorente Guerrero, J., additional, Uria Oficialdegui, M. L., additional, Carrasco, E., additional, and Diaz-de-Heredia, C., additional
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- 2021
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39. The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
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Lakeman, I.M.M., Broek, A.J. van den, Vos, Janet R., Barnes, D.R., Adlard, J., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Balmaña, J., Barrowdale, D., Benitez, J., Borg, A., Caldés, T., Caligo, M.A., Chung, W.K., Claes, K.B.M., Collée, J.M., Couch, F.J., Daly, M.B., Dennis, J., Dhawan, M., Domchek, S.M., Eeles, R., Engel, C., Evans, D.G., Feliubadaló, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Godwin, A.K., Goldgar, D.E., Hahnen, E., Hake, C.R., Hamann, U., Hogervorst, F.B., Hooning, M.J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P.A., Janavicius, R., Jensen, U.B., Jiao, Y., John, E.M., Joseph, V., Karlan, B.Y., Kets, C.M., Konstantopoulou, I., Kwong, A., Legrand, C., Leslie, G., Lesueur, F., Loud, J.T., Lubiński, J., Manoukian, S., McGuffog, L., Miller, A., Gomes, D.M., Montagna, M., Mouret-Fourme, E., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Yie, J.N.Y., Olah, E., Olopade, O.I., Park, S.K., Parsons, M.T., Peterlongo, P., Piedmonte, M., Radice, P., Rantala, J., Rennert, G., Risch, H.A., Schmutzler, R.K., Sharma, P., Simard, J., Singer, C.F., Stadler, Z., Stoppa-Lyonnet, D., Sutter, C., Tan, Y.Y., Teixeira, M.R., Teo, S.H., Teulé, A., Thomassen, M., Thull, D.L., Tischkowitz, M., Toland, A.E., Tung, N., Rensburg, E.J. van, Vega, A., Robson, M., Schmidt, M.K., Lakeman, I.M.M., Broek, A.J. van den, Vos, Janet R., Barnes, D.R., Adlard, J., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Balmaña, J., Barrowdale, D., Benitez, J., Borg, A., Caldés, T., Caligo, M.A., Chung, W.K., Claes, K.B.M., Collée, J.M., Couch, F.J., Daly, M.B., Dennis, J., Dhawan, M., Domchek, S.M., Eeles, R., Engel, C., Evans, D.G., Feliubadaló, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Godwin, A.K., Goldgar, D.E., Hahnen, E., Hake, C.R., Hamann, U., Hogervorst, F.B., Hooning, M.J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P.A., Janavicius, R., Jensen, U.B., Jiao, Y., John, E.M., Joseph, V., Karlan, B.Y., Kets, C.M., Konstantopoulou, I., Kwong, A., Legrand, C., Leslie, G., Lesueur, F., Loud, J.T., Lubiński, J., Manoukian, S., McGuffog, L., Miller, A., Gomes, D.M., Montagna, M., Mouret-Fourme, E., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Yie, J.N.Y., Olah, E., Olopade, O.I., Park, S.K., Parsons, M.T., Peterlongo, P., Piedmonte, M., Radice, P., Rantala, J., Rennert, G., Risch, H.A., Schmutzler, R.K., Sharma, P., Simard, J., Singer, C.F., Stadler, Z., Stoppa-Lyonnet, D., Sutter, C., Tan, Y.Y., Teixeira, M.R., Teo, S.H., Teulé, A., Thomassen, M., Thull, D.L., Tischkowitz, M., Toland, A.E., Tung, N., Rensburg, E.J. van, Vega, A., Robson, M., and Schmidt, M.K.
- Abstract
Contains fulltext : 244113.pdf (Publisher’s version ) (Open Access), PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS(313)) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS(313) and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS(313) showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS(313), HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS(313) 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS(313) can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS(313) needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
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- 2021
40. Overview of hereditary breast and ovarian cancer (HBOC) guidelines across Europe
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Marmolejo, D.H., Wong, M.Y.Z., Hoogerbrugge, N., Bajalica-Lagercrantz, S., Tischkowitz, M., Balmaña, J., Marmolejo, D.H., Wong, M.Y.Z., Hoogerbrugge, N., Bajalica-Lagercrantz, S., Tischkowitz, M., and Balmaña, J.
- Abstract
Item does not contain fulltext, Hereditary breast and ovarian cancer (HBOC) is a syndrome defined by an increased risk of developing breast and/or ovarian cancer most commonly due to germline disease-causing variants in the BRCA1 and BRCA2 genes, but also other causative genes such as PALB2, ATM and CHEK2. As genetic testing becomes more prevalent and new clinical data emerge, updates of national guidelines are required to incorporate these advances in our knowledge. The aim of this work is to review the guidelines for HBOC genetic testing and clinical surveillance across European countries, mostly affiliated to the European Reference Network (ERN) for Genetic Tumor Risk Syndroms (GENTURIS). Young onset breast cancer (BC), triple negative phenotype, or bilateral BC are considered as criteria for genetic testing in all, with differences in age limits. Testing of invasive epithelial non-mucinous ovarian cancer is also universally accepted. While breast magnetic resonance imaging (MRI) is consistently recommended in high-risk individuals, age of onset for mammograms differ between 30 and 40 years. Risk-reducing mastectomy is commonly offered as an option, while risk-reducing salpingo-oophorectomy is universally recommended. The largest differences are observed with respect to ovarian surveillance prior to risk-reducing salpingo-oophorectomy and in breast surveillance for carriers of non-BRCA1/2 genes. These differences in national guidelines reflect the variations in clinical consensus that may be reached in the absence of consistent evidence for some recommendations.
- Published
- 2021
41. Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.
- Author
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UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Condorelli, M, Bruzzone, M, Ceppi, M, Ferrari, A, Grinshpun, A, Hamy, A S, de Azambuja, E, Carrasco, E, Peccatori, F A, Di Meglio, A, Paluch-Shimon, S, Poorvu, P D, Venturelli, M, Rousset-Jablonski, C, Senechal, C, Livraghi, L, Ponzone, R, De Marchis, L, Pogoda, K, Sonnenblick, A, Villarreal-Garza, C, Córdoba, O, Teixeira, L, Clatot, F, Punie, K, Graffeo, R, Dieci, M V, Pérez-Fidalgo, J A, Duhoux, Francois, Puglisi, F, Ferreira, A R, Blondeaux, E, Peretz-Yablonski, T, Caron, O, Saule, C, Ameye, L, Balmaña, J, Partridge, A H, Azim, H A, Demeestere, I, Lambertini, M, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Condorelli, M, Bruzzone, M, Ceppi, M, Ferrari, A, Grinshpun, A, Hamy, A S, de Azambuja, E, Carrasco, E, Peccatori, F A, Di Meglio, A, Paluch-Shimon, S, Poorvu, P D, Venturelli, M, Rousset-Jablonski, C, Senechal, C, Livraghi, L, Ponzone, R, De Marchis, L, Pogoda, K, Sonnenblick, A, Villarreal-Garza, C, Córdoba, O, Teixeira, L, Clatot, F, Punie, K, Graffeo, R, Dieci, M V, Pérez-Fidalgo, J A, Duhoux, Francois, Puglisi, F, Ferreira, A R, Blondeaux, E, Peretz-Yablonski, T, Caron, O, Saule, C, Ameye, L, Balmaña, J, Partridge, A H, Azim, H A, Demeestere, I, and Lambertini, M
- Abstract
Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testi
- Published
- 2021
42. Low penetrance hereditary retinoblastoma in a family: what should we consider in the genetic counselling process and follow up?
- Author
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Serrano, C., Alonso, J., Gómez-Mariano, G., Aguirre, E., Diez, O., Gadea, N., Bosch, N., Balmaña, J., and Graña, B.
- Published
- 2011
- Full Text
- View/download PDF
43. Germline ATM mutational analysis in BRCA1/BRCA2 negative hereditary breast cancer families by MALDI-TOF mass spectrometry
- Author
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Graña, B., Fachal, L., Darder, E., Balmaña, J., Ramón y Cajal, T., Blanco, I., Torres, A., Lázaro, C., Diez, O., Alonso, C., Santamariña, M., Velasco, A., Teulé, A., Lasa, A., Blanco, A., Izquierdo, A., Borràs, J., Gutiérrez-Enríquez, S., Vega, A., and Brunet, J.
- Published
- 2011
- Full Text
- View/download PDF
44. 2O Association of RAD51 with homologous recombination deficiency (HRD) and clinical outcomes in untreated triple-negative breast cancer (TNBC): Analysis of the GeparSixto randomized clinical trial
- Author
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Llop-Guevara, A., primary, Vladimirova, V., additional, Schneeweiss, A., additional, Villacampa, G., additional, Karn, T., additional, Zahm, D-M., additional, Herencia-Ropero, A., additional, Jank, P., additional, van Mackelenbergh, M., additional, Fasching, P.A., additional, Marmé, F., additional, Stickeler, E., additional, Schem, C., additional, Dienstmann, R., additional, Florian, S., additional, Nekljudova, V., additional, Balmaña, J., additional, Denkert, C., additional, Loibl, S., additional, and Serra, V., additional
- Published
- 2021
- Full Text
- View/download PDF
45. 1O Detection of homologous recombination repair deficiency (HRD) in treatment-naive early triple-negative breast cancer (TNBC) by RAD51 foci and comparison with DNA-based tests
- Author
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Serra Elizalde, V., primary, Llop-Guevara, A., additional, Pearson, A., additional, Cruz, C., additional, Castroviejo-Bermejo, M., additional, Chopra, N., additional, Tovey, H., additional, Toms, C., additional, Kriplani, D., additional, Gevensleben, H., additional, Roylance, R., additional, Chan, S., additional, Tutt, A., additional, Skene, A., additional, Evans, A., additional, Davies, H.R., additional, Bliss, J., additional, Nik-Zainal, S., additional, Balmaña, J., additional, and Turner, N., additional
- Published
- 2021
- Full Text
- View/download PDF
46. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes
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Fachal, L., Aschard, H., Beesley, J., Barnes, D.R., Allen, J., Kar, S., Pooley, K.A., Dennis, J., Michailidou, K., Turman, C., Soucy, P., Lemaçon, A., Lush, M., Tyrer, J.P., Ghoussaini, M., Marjaneh, M.M., Jiang, X., Agata, S., Aittomäki, K., Alonso, M.R., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arason, A., Arndt, V., Aronson, K.J., Arun, B.K., Auber, B., Auer, P.L., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Białkowska, K., Blanco, A.M., Blomqvist, C., Blot, W., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bonanni, B., Borg, A., Bosse, K., Brauch, H., Brenner, H., Briceno, I., Brock, I.W., Brooks-Wilson, A., Brüning, T., Burwinkel, B., Buys, S.S., Cai, Q., Caldés, T., Caligo, M.A., Camp, N.J., Campbell, I., Canzian, F., Carroll, J.S., Carter, B.D., Castelao, J.E., Chiquette, J., Christiansen, H., Chung, W.K., Claes, K.B.M., Clarke, C.L., Mari, V., Berthet, P., Castera, L., Vaur, D., Lallaoui, H., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Lasset, C., Révillion, F., Vennin, P., Muller, D., Gomes, D.M., Ingster, O., Coupier, I., Pujol, P., Collonge-Rame, M.-A., Mortemousque, I., Bera, O., Rose, M., Baurand, A., Bertolone, G., Faivre, L., Dreyfus, H., Leroux, D., Venat-Bouvet, L., Bézieau, S., Delnatte, C., Chiesa, J., Gilbert-Dussardier, B., Gesta, P., Prieur, F.P., Bronner, M., Sokolowska, J., Coulet, F., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Fert-Ferrer, S., Stoppa-Lyonnet, D., Jiao, Y., Lesueur, F.L., Mebirouk, N., Barouk-Simonet, E., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Toulas, C., Reimineras, A., Sobol, H., Paillerets, B.B.-D., Cabaret, O., Caron, O., Guillaud-Bataille, M., Rouleau, E., Belotti, M., Buecher, B., Caputo, S., Colas, C., Pauw, A.D., Fourme, E., Gauthier-Villars, M., Golmard, L., Moncoutier, V., Saule, C., Donaldson, A., Murray, A., Brady, A., Brewer, C., Pottinger, C., Miller, C., Gallagher, D., Gregory, H., Cook, J., Eason, J., Adlard, J., Barwell, J., Ong, K.-R., Snape, K., Walker, L., Izatt, L., Side, L., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Ahmed, M., Morrison, P.J., Brennan, P., Eeles, R., Davidson, R., Collée, M., Cornelissen, S., Couch, F.J., Cox, A., Cross, S.S., Cybulski, C., Czene, K., Daly, M.B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y.C., Dite, G.S., Domchek, S.M., Dörk, T., dos-Santos-Silva, I., Droit, A., Dubois, S., Dumont, M., Duran, M., Durcan, L., Dwek, M., Eccles, D.M., Engel, C., Eriksson, M., Evans, D.G., Fasching, P.A., Fletcher, O., Floris, G., Flyger, H., Foretova, L., Foulkes, W.D., Friedman, E., Fritschi, L., Frost, D., Gabrielson, M., Gago-Dominguez, M., Gambino, G., Ganz, P.A., Gapstur, S.M., Garber, J., García-Sáenz, J.A., Gaudet, M.M., Georgoulias, V., Giles, G., Glendon, G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., González-Neira, A., Tibiletti, M.G., Greene, M.H., Grip, M., Gronwald, J., Grundy, A., Guénel, P., Hahnen, E., Haiman, C.A., Håkansson, N., Hall, P., Hamann, U., Harrington, P.A., Hartikainen, J.M., Hartman, M., He, W., Healey, C.S., Heemskerk-Gerritsen, B.A.M., Heyworth, J., Hillemanns, P., Hogervorst, F.B.L., Hollestelle, A., Hooning, M., Hopper, J., Howell, A., Huang, G., Hulick, P.J., Imyanitov, E.N., Sexton, A., Christian, A., Trainer, A., Spigelman, A., Fellows, A., Shelling, A., Fazio, A.D., Blackburn, A., Crook, A., Meiser, B., Patterson, B., Clarke, C., Saunders, C., Hunt, C., Scott, C., Amor, D., Marsh, D., Edkins, E., Salisbury, E., Haan, E., Neidermayr, E., Macrea, F., Farshid, G., Lindeman, G., Chenevix-Trench, G., Mann, G., Gill, G., Thorne, H., Hickie, I., Winship, I., Flanagan, J., Kollias, J., Visvader, J., Stone, J., Taylor, J., Burke, J., Saunus, J., Forbes, J., Kirk, J., French, J., Tucker, K., Wu, K., Phillips, K., Lipton, L., Andrews, L., Lobb, L., Kentwell, M., Spurdle, M., Cummings, M., Gleeson, M., Harris, M., Jenkins, M., Young, M.A., Delatycki, M., Wallis, M., Burgess, M., Price, M., Brown, M., Southey, M., Bogwitz, M., Field, M., Friedlander, M., Gattas, M., Saleh, M., Hayward, N., Pachter, N., Cohen, P., Duijf, P., James, P., Simpson, P., Fong, P., Butow, P., Williams, R., Kefford, R., Scott, R., Milne, R.L., Balleine, R., Dawson, S.–J., Lok, S., O’Connell, S., Greening, S., Nightingale, S., Edwards, S., Fox, S., McLachlan, S.-A., Lakhani, S., Antill, Y., Aalfs, C., Meijers-Heijboer, H., van Engelen, K., Gille, H., Boere, I., van Deurzen, C., Obdeijn, I.-M., van den Ouweland, A., Seynaeve, C., Siesling, S., Verloop, J., van Asperen, C.J., van Cronenburg, T., Blok, R., de Boer, M., Garcia, E.G., Adank, M., Hogervorst, F., Jenner, D., van Leeuwen, F., Rookus, M., Russell, N., Schmidt, M., van den Belt-Dusebout, S., Kets, C., Mensenkamp, A., de Bock, T., van der Hout, A., Mourits, M., Oosterwijk, J., Ausems, M., Koudijs, M., Baxter, R., Yip, D., Carpenter, J., Davis, A., Pathmanathan, N., Graham, D., Sachchithananthan, M., Isaacs, C., Iwasaki, M., Jager, A., Jakimovska, M., Jakubowska, A., James, P.A., Janavicius, R., Jankowitz, R.C., John, E.M., Johnson, N., Jones, M.E., Jukkola-Vuorinen, A., Jung, A., Kaaks, R., Kang, D., Kapoor, P.M., Karlan, B.Y., Keeman, R., Kerin, M.J., Khusnutdinova, E., Kiiski, J.I., Kitahara, C.M., Ko, Y.-D., Konstantopoulou, I., Kosma, V.-M., Koutros, S., Kubelka-Sabit, K., Kwong, A., Kyriacou, K., Laitman, Y., Lambrechts, D., Lee, E., Leslie, G., Lester, J., Lesueur, F., Lindblom, A., Lo, W.-Y., Long, J., Lophatananon, A., Loud, J.T., Lubiński, J., MacInnis, R.J., Maishman, T., Makalic, E., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Matsuo, K., Maurer, T., Mavroudis, D., Mayes, R., McGuffog, L., McLean, C., Meindl, A., Miller, A., Miller, N., Montagna, M., Moreno, F., Muir, K., Mulligan, A.M., Muñoz-Garzon, V.M., Muranen, T.A., Narod, S.A., Nassir, R., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Neven, P., Nielsen, F.C., Nikitina-Zake, L., Norman, A., Offit, K., Olah, E., Olopade, O.I., Olsson, H., Orr, N., Osorio, A., Pankratz, V.S., Papp, J., Park, S.K., Park-Simon, T.-W., Parsons, M.T., Paul, J., Pedersen, I.S., Peissel, B., Peshkin, B., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Presneau, N., Prokofyeva, D., Pujana, M.A., Pylkäs, K., Radice, P., Ramus, S.J., Rantala, J., Rau-Murthy, R., Rennert, G., Risch, H.A., Robson, M., Romero, A., Rossing, M., Saloustros, E., Sánchez-Herrero, E., Sandler, D.P., Santamariña, M., Sawyer, E.J., Scheuner, M.T., Schmidt, D.F., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Schöttker, B., Schürmann, P., Scott, R.J., Senter, L., Seynaeve, C.M., Shah, M., Sharma, P., Shen, C.-Y., Shu, X.-O., Singer, C.F., Slavin, T.P., Smichkoska, S., Southey, M.C., Spinelli, J.J., Spurdle, A.B., Sutter, C., Swerdlow, A.J., Tamimi, R.M., Tan, Y.Y., Tapper, W.J., Taylor, J.A., Teixeira, M.R., Tengström, M., Teo, S.H., Terry, M.B., Teulé, A., Thomassen, M., Thull, D.L., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Torres, D., Torres-Mejía, G., Troester, M.A., Truong, T., Tung, N., Tzardi, M., Ulmer, H.-U., Vachon, C.M., van der Kolk, L.E., van Rensburg, E.J., Vega, A., Viel, A., Vijai, J., Vogel, M.J., Wang, Q., Wappenschmidt, B., Weinberg, C.R., Weitzel, J.N., Wendt, C., Wildiers, H., Winqvist, R., Wolk, A., Wu, A.H., Yannoukakos, D., Zhang, Y., Zheng, W., Hunter, D., Pharoah, P.D.P., Chang-Claude, J., García-Closas, M., Schmidt, M.K., Kristensen, V.N., French, J.D., Edwards, S.L., Antoniou, A.C., Simard, J., Easton, D.F., Kraft, P., Dunning, A.M., Collaborators, GEMO Study, Collaborators, EMBRACE, Investigators, KConFab, Investigators, HEBON, Investigators, ABCTB, Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R, Duijf, Pascal, Dunning, Alison M, GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), European Commission, Government of Canada, Canadian Institutes of Health Research, National Institutes of Health (US), Cancer Research UK, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, University of Cambridge [UK] (CAM), NSCAD, University of Cyprus [Nicosia], Harvard T.H. Chan School of Public Health, This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation), the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492), and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note., We thank all of the individuals who took part in these studies, as well as all of the researchers, clinicians, technicians and administrative staff who enabled this work to be carried out, European Project: 656144,H2020,H2020-MSCA-IF-2014,RADIOGENFF(2016), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), Clinical Genetics, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia] (UCY), 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, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Targeted Gynaecologic Oncology (TARGON), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Aschard, Hugues [0000-0002-7554-6783], Barnes, Daniel R [0000-0002-3781-7570], Dennis, Joe [0000-0003-4591-1214], Michailidou, Kyriaki [0000-0001-7065-1237], Lemaçon, Audrey [0000-0002-1817-7029], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Bojesen, Stig E [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Campbell, Ian [0000-0002-7773-4155], Carroll, Jason S [0000-0003-3643-0080], Claes, Kathleen BM [0000-0003-0841-7372], Collée, J Margriet [0000-0002-9272-9346], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dwek, Miriam [0000-0001-7184-2932], Fletcher, Olivia [0000-0001-9387-7116], Floris, Giuseppe [0000-0003-2391-5425], Foulkes, William D [0000-0001-7427-4651], García-Sáenz, José A [0000-0001-6880-0301], Greene, Mark H [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Heemskerk-Gerritsen, Bernadette AM [0000-0002-9724-6693], Hollestelle, Antoinette [0000-0003-1166-1966], Hulick, Peter J [0000-0001-8397-4078], Jakimovska, Milena [0000-0002-1506-0669], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Konstantopoulou, Irene [0000-0002-0470-0309], Leslie, Goska [0000-0001-5756-6222], Lesueur, Fabienne [0000-0001-7404-4549], Matsuo, Keitaro [0000-0003-1761-6314], McLean, Catriona [0000-0002-0302-5727], Miller, Austin [0000-0001-9739-8462], Muir, Kenneth [0000-0001-6429-988X], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I [0000-0002-9936-1599], Orr, Nick [0000-0003-2866-942X], Pankratz, V Shane [0000-0002-3742-040X], Parsons, Michael T [0000-0003-3242-8477], Paul, James [0000-0001-7367-5816], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Pylkäs, Katri [0000-0002-2449-0521], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Robson, Mark [0000-0002-3109-1692], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Scott, Rodney J [0000-0001-7724-3404], Spurdle, Amanda B [0000-0003-1337-7897], Stone, Jennifer [0000-0001-5077-0124], Sutter, Christian [0000-0003-4051-5888], Tan, Yen Yen [0000-0003-1063-5352], Teixeira, Manuel R [0000-0002-4896-5982], Toland, Amanda E [0000-0002-0271-1792], Tomlinson, Ian [0000-0003-3037-1470], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Pharoah, Paul DP [0000-0001-8494-732X], Schmidt, Marjanka K [0000-0002-2228-429X], Milne, Roger L [0000-0001-5764-7268], Edwards, Stacey L [0000-0001-7428-4139], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Kraft, Peter [0000-0002-4472-8103], Dunning, Alison M [0000-0001-6651-7166], Apollo - University of Cambridge Repository, Academic Medical Center, ARD - Amsterdam Reproduction and Development, Human genetics, CCA - Cancer biology and immunology, Molecular cell biology and Immunology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, University of Helsinki, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Doctoral Programme in Clinical Research, Staff Services, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, and Department of Obstetrics and Gynecology
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CHROMATIN ,Linkage disequilibrium ,Genome-wide association study ,Regulatory Sequences, Nucleic Acid ,Genome-wide association studies ,Linkage Disequilibrium ,Basic medicine ,0302 clinical medicine ,Breast cancer ,MESH: Risk Factors ,Risk Factors ,COMPREHENSIVE MOLECULAR PORTRAITS ,11 Medical and Health Sciences ,HEBON Investigators ,Genetics & Heredity ,0303 health sciences ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,PROTEIN FUNCTION ,Tumor ,breast tumor ,MESH: Polymorphism, Single Nucleotide ,1184 Genetics, developmental biology, physiology ,MESH: Genetic Predisposition to Disease ,apoptosis ,Chromosome Mapping ,Single Nucleotide ,3. Good health ,MESH: Linkage Disequilibrium ,Female ,MESH: Biomarkers, Tumor ,Biomarkers, Tumor/genetics ,[STAT.ME]Statistics [stat]/Methodology [stat.ME] ,Life Sciences & Biomedicine ,SUSCEPTIBILITY LOCI ,MESH: Bayes Theorem ,Quantitative Trait Loci ,ABCTB Investigators ,INTEGRATIVE ANALYSIS ,Breast Neoplasms ,Computational biology ,Biology ,Quantitative trait locus ,Breast Neoplasms/genetics ,Polymorphism, Single Nucleotide ,Article ,ENHANCER ,GEMO Study Collaborators ,03 medical and health sciences ,breast cancer ,SDG 3 - Good Health and Well-being ,REVEALS ,Genetics ,Biomarkers, Tumor ,MESH: Regulatory Sequences, Nucleic Acid ,Humans ,Genetic Predisposition to Disease ,Polymorphism ,GENOME-WIDE ASSOCIATION ,FUNCTIONAL VARIANTS ,EMBRACE Collaborators ,Gene ,030304 developmental biology ,Genetic association ,Bayes Theorem ,Genome-Wide Association Study ,MESH: Humans ,Science & Technology ,Nucleic Acid ,gene mapping ,06 Biological Sciences ,MESH: Quantitative Trait Loci ,DNA binding site ,ESTROGEN-RECEPTOR ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Clinical medicine ,Expression quantitative trait loci ,MESH: Genome-Wide Association Study ,Human genome ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,KConFab Investigators ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,MESH: Chromosome Mapping ,Chromosome Mapping/methods ,Regulatory Sequences ,MESH: Female ,Biomarkers ,030217 neurology & neurosurgery ,MESH: Breast Neoplasms ,Developmental Biology - Abstract
Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes., This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation); the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE; part of the GAME-ON initiative).
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- 2020
47. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes
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Fachal, L, Aschard, H, Beesley, J, Barnes, DR, Allen, J, Kar, S, Pooley, KA, Dennis, J, Michailidou, K, Turman, C, Soucy, P, Lemaçon, A, Lush, M, Tyrer, JP, Ghoussaini, M, Marjaneh, MM, Jiang, X, Agata, S, Aittomäki, K, Alonso, MR, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arason, A, Arndt, V, Aronson, KJ, Arun, BK, Auber, B, Auer, PL, Azzollini, J, Balmaña, J, Barkardottir, RB, Barrowdale, D, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Białkowska, K, Blanco, AM, Blomqvist, C, Blot, W, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Borg, A, Bosse, K, Brauch, H, Brenner, H, Briceno, I, Brock, IW, Brooks-Wilson, A, Brüning, T, Burwinkel, B, Buys, SS, Cai, Q, Caldés, T, Caligo, MA, Camp, NJ, Campbell, I, Canzian, F, Carroll, JS, Carter, BD, Castelao, JE, Chiquette, J, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Mari, V, Berthet, P, Castera, L, Vaur, D, Lallaoui, H, Bignon, YJ, Uhrhammer, N, Bonadona, V, Lasset, C, Révillion, F, Vennin, P, Muller, D, Gomes, DM, Ingster, O, Coupier, I, Pujol, P, Collonge-Rame, MA, Mortemousque, I, Bera, O, Rose, M, Baurand, A, Bertolone, G, Faivre, L, Dreyfus, H, Leroux, D, Venat-Bouvet, L, Bézieau, S, Delnatte, C, Chiesa, J, Gilbert-Dussardier, B, Gesta, P, and Prieur, FP
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Quantitative Trait Loci ,ABCTB Investigators ,Breast Neoplasms ,Regulatory Sequences, Nucleic Acid ,Polymorphism, Single Nucleotide ,Medical and Health Sciences ,Linkage Disequilibrium ,GEMO Study Collaborators ,Risk Factors ,Breast Cancer ,Biomarkers, Tumor ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Genetic Testing ,Aetiology ,Polymorphism ,EMBRACE Collaborators ,HEBON Investigators ,Cancer ,Tumor ,Nucleic Acid ,Prevention ,Human Genome ,Chromosome Mapping ,Bayes Theorem ,Single Nucleotide ,Biological Sciences ,Female ,KConFab Investigators ,Regulatory Sequences ,Biomarkers ,Genome-Wide Association Study ,Biotechnology ,Developmental Biology - Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.
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- 2020
48. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
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Barnes, D.R., Rookus, Matti A., McGuffog, L., Leslie, G., Mooij, T.M., Dennis, J., Mavaddat, N., Adlard, J., Ahmed, M., Aittomäki, K., Andrieu, N., Andrulis, I.L., Arnold, N., Arun, B.K., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Benitez, J., Berthet, P., Białkowska, K., Blanco, A.M., Blok, M.J., Bonanni, B., Boonen, S.E., Borg, Å., Bozsik, A., Bradbury, A.R., Brennan, P., Brewer, C., Brunet, J., Buys, S.S., Caldés, T., Caligo, M.A., Campbell, I., Christensen, L.L., Chung, W.K., Claes, K.B.M., Colas, C., Collonge-Rame, M.A., Cook, J., Daly, M.B., Davidson, R., Hoya, M. de la, Putter, R. de, Delnatte, C., Devilee, P., Diez, O., Ding, Y.C., Domchek, S.M., Dorfling, C.M., Dumont, M., Eeles, R., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Foretova, L., Fostira, F., Friedlander, M., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gehrig, A., Gerdes, A.M., Gesta, P., Giraud, S., Glendon, G., Godwin, A.K., Goldgar, D.E., González-Neira, A., Greene, M.H., Gschwantler-Kaulich, D., Hahnen, E., Hamann, U., Hanson, H., Hentschel, J., Hogervorst, F.B., Hooning, M.J., Horvath, J., Hu, C., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Izquierdo, A., Jakubowska, A., James, P.A., Janavicius, R., John, E.M., Joseph, V., Karlan, B.Y., Kast, K., Koudijs, M., Kruse, T.A., Kwong, A., Laitman, Y., Lasset, C., Mensenkamp, A.R., Chenevix-Trench, G., Antoniou, A.C., Barnes, D.R., Rookus, Matti A., McGuffog, L., Leslie, G., Mooij, T.M., Dennis, J., Mavaddat, N., Adlard, J., Ahmed, M., Aittomäki, K., Andrieu, N., Andrulis, I.L., Arnold, N., Arun, B.K., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Benitez, J., Berthet, P., Białkowska, K., Blanco, A.M., Blok, M.J., Bonanni, B., Boonen, S.E., Borg, Å., Bozsik, A., Bradbury, A.R., Brennan, P., Brewer, C., Brunet, J., Buys, S.S., Caldés, T., Caligo, M.A., Campbell, I., Christensen, L.L., Chung, W.K., Claes, K.B.M., Colas, C., Collonge-Rame, M.A., Cook, J., Daly, M.B., Davidson, R., Hoya, M. de la, Putter, R. de, Delnatte, C., Devilee, P., Diez, O., Ding, Y.C., Domchek, S.M., Dorfling, C.M., Dumont, M., Eeles, R., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Foretova, L., Fostira, F., Friedlander, M., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Gehrig, A., Gerdes, A.M., Gesta, P., Giraud, S., Glendon, G., Godwin, A.K., Goldgar, D.E., González-Neira, A., Greene, M.H., Gschwantler-Kaulich, D., Hahnen, E., Hamann, U., Hanson, H., Hentschel, J., Hogervorst, F.B., Hooning, M.J., Horvath, J., Hu, C., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Izquierdo, A., Jakubowska, A., James, P.A., Janavicius, R., John, E.M., Joseph, V., Karlan, B.Y., Kast, K., Koudijs, M., Kruse, T.A., Kwong, A., Laitman, Y., Lasset, C., Mensenkamp, A.R., Chenevix-Trench, G., and Antoniou, A.C.
- Abstract
Contains fulltext : 229292.pdf (Publisher’s version ) (Open Access), PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10(-72)). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10(-22)) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10(-12)) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
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- 2020
49. Reply to Kratz et al.
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Frebourg, T. (Thierry), Lagercrantz, S.B. (Svetlana Bajalica), Oliveira, C. (Carla), Magenheim, R. (Rita), Evans, D.G. (D. Gareth), Hoogerbrugge, N. (Nicoline), Ligtenberg, M.J. (Marjolijn), Oostenbrink, R. (Rianne), Sijmons, R.H. (Rolf), Woodward, E.R. (Emma R.), Tischkowitz, M. (Marc), Maher, E.R. (Eamonn), Ferner, R.E. (Rosalie E.), Aretz, S. (Stefan), Spier, I. (Isabel), Steinke-Lange, V. (Verena), Holinski-Feder, E. (Elke), Schröck, E. (Evelin), Houdayer, C. (Claude), Colas, C. (Chrystelle), Wolkenstein, P. (Pierre), Bours, V. (Vincent), Legius, E. (Eric), Poppe, B. (Bruce), Claes, K. (Kathleen), de Putter, R. (Robin), Guillermo, I.B. (Ignacio Blanco), Capellá, G. (Gabriel), Vidal, J.B. (Joan Brunet), Lázaro, C. (Conxi), Balmaña, J. (Judith), Hernandez, H.S. (Hector Salvador), Teixeira, M. (Manuel), Tham, E. (Emma), Jan, L. (Lubinski), Ertmanska, K. (Karolina), Melegh, B. (Bela), Krajc, M. (Mateja), Blatnik, A. (Ana), Peltonen, S. (Sirkku), Hietala, M. (Marja), Frebourg, T. (Thierry), Lagercrantz, S.B. (Svetlana Bajalica), Oliveira, C. (Carla), Magenheim, R. (Rita), Evans, D.G. (D. Gareth), Hoogerbrugge, N. (Nicoline), Ligtenberg, M.J. (Marjolijn), Oostenbrink, R. (Rianne), Sijmons, R.H. (Rolf), Woodward, E.R. (Emma R.), Tischkowitz, M. (Marc), Maher, E.R. (Eamonn), Ferner, R.E. (Rosalie E.), Aretz, S. (Stefan), Spier, I. (Isabel), Steinke-Lange, V. (Verena), Holinski-Feder, E. (Elke), Schröck, E. (Evelin), Houdayer, C. (Claude), Colas, C. (Chrystelle), Wolkenstein, P. (Pierre), Bours, V. (Vincent), Legius, E. (Eric), Poppe, B. (Bruce), Claes, K. (Kathleen), de Putter, R. (Robin), Guillermo, I.B. (Ignacio Blanco), Capellá, G. (Gabriel), Vidal, J.B. (Joan Brunet), Lázaro, C. (Conxi), Balmaña, J. (Judith), Hernandez, H.S. (Hector Salvador), Teixeira, M. (Manuel), Tham, E. (Emma), Jan, L. (Lubinski), Ertmanska, K. (Karolina), Melegh, B. (Bela), Krajc, M. (Mateja), Blatnik, A. (Ana), Peltonen, S. (Sirkku), and Hietala, M. (Marja)
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- 2020
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50. Guidelines for the Li–Fraumeni and heritable TP53-related cancer syndromes
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Frebourg, T. (Thierry), Bajalica Lagercrantz, S. (Svetlana), Oliveira, C. (Carla), Magenheim, R. (Rita), Evans, D.G. (D. Gareth), Hoogerbrugge, N. (Nicoline), Ligtenberg, M.J. (Marjolijn), Kets, C.M. (Marleen), Oostenbrink, R. (Rianne), Sijmons, R.H. (Rolf), Evans, G. (Gareth), Woodward, E.R. (Emma R.), Tischkowitz, M. (Marc), Maher, E.R. (Eamonn), Ferner, R.E. (Rosalie E.), Aretz, S. (Stefan), Spier, I. (Isabel), Steinke-Lange, V. (Verena), Holinski-Feder, E. (Elke), Schröck, E. (Evelin), Houdayer, C. (Claude), Colas, C. (Chrystelle), Wolkenstein, P. (Pierre), Bours, V. (Vincent), Legius, E. (Eric), Poppe, B. (Bruce), Claes, K. (Kathleen), de Putter, R. (Robin), Guillermo, I.B. (Ignacio Blanco), Capellá, G. (Gabriel), Vidal, J.B. (Joan Brunet), Lázaro, C. (Conxi), Balmaña, J. (Judith), Hernandez, H.S. (Hector Salvador), Teixeira, P.J., Tham, E. (Emma), Lubinski, J. (Jan), Ertmanska, K. (Karolina), Melegh, B. (Bela), Krajc, M. (Mateja), Blatnik, A. (Ana), Peltonen, S. (Sirkku), Hietala, M. (Marja), Frebourg, T. (Thierry), Bajalica Lagercrantz, S. (Svetlana), Oliveira, C. (Carla), Magenheim, R. (Rita), Evans, D.G. (D. Gareth), Hoogerbrugge, N. (Nicoline), Ligtenberg, M.J. (Marjolijn), Kets, C.M. (Marleen), Oostenbrink, R. (Rianne), Sijmons, R.H. (Rolf), Evans, G. (Gareth), Woodward, E.R. (Emma R.), Tischkowitz, M. (Marc), Maher, E.R. (Eamonn), Ferner, R.E. (Rosalie E.), Aretz, S. (Stefan), Spier, I. (Isabel), Steinke-Lange, V. (Verena), Holinski-Feder, E. (Elke), Schröck, E. (Evelin), Houdayer, C. (Claude), Colas, C. (Chrystelle), Wolkenstein, P. (Pierre), Bours, V. (Vincent), Legius, E. (Eric), Poppe, B. (Bruce), Claes, K. (Kathleen), de Putter, R. (Robin), Guillermo, I.B. (Ignacio Blanco), Capellá, G. (Gabriel), Vidal, J.B. (Joan Brunet), Lázaro, C. (Conxi), Balmaña, J. (Judith), Hernandez, H.S. (Hector Salvador), Teixeira, P.J., Tham, E. (Emma), Lubinski, J. (Jan), Ertmanska, K. (Karolina), Melegh, B. (Bela), Krajc, M. (Mateja), Blatnik, A. (Ana), Peltonen, S. (Sirkku), and Hietala, M. (Marja)
- Abstract
Fifty years after the recognition of the Li–Fraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher canc
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- 2020
- Full Text
- View/download PDF
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