Search

Your search keyword '"Colas C."' showing total 683 results
Start Over Author "Colas C."
683 results on '"Colas C."'

1. The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients

Author

Baz, M., Gondran-Teiller, V., Bressac, B., Cabaret, O., Fievet, A., Dimaria, M., Goldbarg, V., Colas, C., Bonnet-Dupeyron, M. N., Tinat, J., Lebrun, M., Mari, V., Limacher, J. M., Corsini, C., Ginglinger, E., Saurin, J. C., Brahimi, A., Rouzier, C., Giraud, S., Schuster, H., Hollebecque, A., Boige, V., Cauchin, E., Malka, D., Caron, O., and Rouleau, E.

Published
2023
Full Text
View/download PDF

9. Results of a 1-year quality-improvement process to reduce door-to-needle time in acute ischemic stroke with MRI screening

Author

Sablot, D., Gaillard, N., Colas, C., Smadja, P., Gely, C., Dutray, A., Bonnec, J.-M., Jurici, S., Farouil, G., Ferraro-Allou, A., Jantac, M., Allou, T., Pujol, C., Olivier, N., Laverdure, A., Fadat, B., Mas, J., Dumitrana, A., Garcia, Y., Touzani, H., Perucho, P., Moulin, T., Richard, C., Heroum, C., Bouly, S., Sagnes-Raffy, C., and Heve, D.

Published
2017
Full Text
View/download PDF

12. Cancer risks by sex and variant type in PTEN hamartoma tumor syndrome.

Author

Hendricks, L.A.J., Hoogerbrugge, N., Mensenkamp, A.R., Brunet, J., Lleuger-Pujol, R., Høberg-Vetti, H., Tveit Haavind, M., Innella, G., Turchetti, D., Aretz, S., Spier, I., Tischkowitz, M., Jahn, A., Links, T.P., Olderode-Berends, M.J., Blatnik, A., Leter, E.M., Evans, D.G., Woodward, E.R., Steinke-Lange, V., Anastasiadou, V.C., Colas, C., Villy, M.C., Benusiglio, P.R., Gerasimenko, A., Barili, V., Branchaud, M., Houdayer, C., Tesi, B., Yazicioglu, M.O., Post, R.S. van der, Schuurs-Hoeijmakers, J.H.M., Vos, J.R., Hendricks, L.A.J., Hoogerbrugge, N., Mensenkamp, A.R., Brunet, J., Lleuger-Pujol, R., Høberg-Vetti, H., Tveit Haavind, M., Innella, G., Turchetti, D., Aretz, S., Spier, I., Tischkowitz, M., Jahn, A., Links, T.P., Olderode-Berends, M.J., Blatnik, A., Leter, E.M., Evans, D.G., Woodward, E.R., Steinke-Lange, V., Anastasiadou, V.C., Colas, C., Villy, M.C., Benusiglio, P.R., Gerasimenko, A., Barili, V., Branchaud, M., Houdayer, C., Tesi, B., Yazicioglu, M.O., Post, R.S. van der, Schuurs-Hoeijmakers, J.H.M., and Vos, J.R.

Abstract

Item does not contain fulltext, BACKGROUND: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks. METHODS: This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses. RESULTS: A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range = 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] = 43.0% to 66.4%) to 75.8% (95% CI = 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI = 2.1% to 18.6%) to 22.1% (95% CI = 11.6% to 39.6%) and TC risks from 8.9% (95% CI = 5.1% to 15.3%) to 20.5% (95% CI = 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%. CONCLUSIONS: Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management.

Published
2023

13. High yield of surveillance in patients diagnosed with constitutional mismatch repair deficiency

Author

Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., Vasen, H.F.A., Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., and Vasen, H.F.A.

Abstract

Contains fulltext : 294692.pdf (Publisher’s version ) (Closed access), BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessively inherited syndrome that is caused by biallelic pathogenic variants of the mismatch repair genes. It is characterised by the development of multiple tumours in the first and second decade of life including brain, gastrointestinal and haematological tumours often resulting in early death. In order to improve the prognosis of these patients, the European collaborative group 'care for CMMRD' developed a surveillance programme in 2014 and established a registry of patients with CMMRD in Paris. The aim of the study was to evaluate the outcome of this programme. METHODS: Twenty-two patients with a definitive diagnosis of CMMRD and with at least one follow-up study were selected from the registry. Medical data on the outcome of surveillance were collected from these patients. RESULTS: During a mean follow-up of 4 years, the programme detected eight malignant tumours including three brain tumours, three upper gastrointestinal cancers and two colorectal cancers. Most tumours could successfully be treated. In addition, many adenomas were detected in the duodenum, and colorectum and subsequently removed. Seven patients developed a symptomatic malignancy, including two brain tumours, one small bowel cancer and four haematological malignancies. At the end of the follow-up, 16 out of 22 patients (73%) who participated in the surveillance programme were still alive. CONCLUSION: The study suggests a beneficial effect of surveillance of the digestive tract and brains.

Published
2023

19. The multinational second Diabetes, Attitudes, Wishes and Needs study: results of the French survey

Author

Reach G, Consoli SM, Halimi S, Colas C, Duclos M, Fontaine P, Martineau C, Avril C, Tourette-Turgis C, Pucheu S, and Brunet O

Subjects
Medicine (General), R5-920
Abstract

Gérard Reach,1,2 Silla M Consoli,3,4 Serge Halimi,5 Claude Colas,6 Martine Duclos,7–9 Pierre Fontaine,10 Caroline Martineau,11 Carole Avril,12 Catherine Tourette-Turgis,13 Sylvie Pucheu,4 Olivier Brunet14 1Department of Endocrinology, Diabetes and Metabolic Diseases, Avicenne Hospital, Bobigny, 2EA 3412, CRNH-IDF, Paris 13 University, Sorbonne Paris Cité, Bobigny, 3Paris Descartes University, Paris Sorbonne Cité, Faculty of Medicine, Paris, 4University Service of Adult and Elderly Psychiatry, European Georges-Pompidou Hospital, Paris, 5Department of Diabetology, Endocrinology and Nutrition, Joseph Fourier University and CHU Grenoble, Grenoble, 6Department of Diabetology, Hôtel-Dieu Hospital, Paris, 7Department of Sport Medicine and Functional Explorations, Montpied Hospital, Clermont-Ferrand, 8Department of Human Nutrition, Centre de Recherche en Nutrition Humaine, Institut National de la Recherche Agronomique, Clermont-Ferrand, 9Department of Human Nutrition, University of Auvergne, Clermont-Ferrand, 10Department of Endocrinology, Diabetes and Metabolic Diseases, Huriez Hospital, Lille 2 University, Lille, 11Department of Dietetics, Larrey Hospital, CHU Toulouse, 12French Diabetics Federation, Paris, 13UPMC-Sorbonne Universités, Paris, 14General practitioner, Seraincourt, France Aim: The second Diabetes, Attitudes, Wishes and Needs (DAWN2™) multinational cross-sectional study was aimed at generating insights to facilitate innovative efforts by people with diabetes (PWD), family members (FMs), and health care professionals (HCPs) to improve self-management and psychosocial support in diabetes. Here, the French data from the DAWN2™ study are described.Methods: In France, 500 PWD (80 with type 1 diabetes [T1] and 420 with type 2 diabetes [T2]), 120 FMs, and 288 HCPs were recruited. The questionnaires assessed the impact of diabetes on quality of life and mood, self-management, attitudes/beliefs, and care/support.Results: Diabetes negatively impacted the emotional well-being of 59% of people with T1 versus 45% of people with T2 (P

Published
2015

20. The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients

Author

Baz, M., primary, Gondran-Teiller, V., additional, Bressac, B., additional, Cabaret, O., additional, Fievet, A., additional, Dimaria, M., additional, Goldbarg, V., additional, Colas, C., additional, Bonnet-Dupeyron, M. N., additional, Tinat, J., additional, Lebrun, M., additional, Mari, V., additional, Limacher, J. M., additional, Corsini, C., additional, Ginglinger, E., additional, Saurin, J. C., additional, Brahimi, A., additional, Rouzier, C., additional, Giraud, S., additional, Schuster, H., additional, Hollebecque, A., additional, Boige, V., additional, Cauchin, E., additional, Malka, D., additional, Caron, O., additional, and Rouleau, E., additional

Published
2022
Full Text
View/download PDF

22. Seroprevalencia de Toxoplasma gondiien Gallus domesticus en La Habana, Cuba

Author

Grandía G., Raiden, Colas C., Manuel, Soroa R., Julio, Entrena G., Ángel, Figueroa B., Teresa, Bada B., Ana, Jáuregui C., Susana, Caraballoso H., Yara, García V., Itamys, Burón R., Miriam, Pérez G., Moraima, Negrin R., Natacha, Pantaleón M., Danny, Frías M., Raydel, Rodríguez L., Ángel, Barrios H., Miguel, and Rodríguez J., Ariam

Published
2016
Full Text
View/download PDF

27. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants

Author

Li, S, Silvestri, V, Leslie, G, Rebbeck, TR, Neuhausen, SL, Hopper, JL, Nielsen, HR, Lee, A, Yang, X, McGuffog, L, Parsons, MT, Andrulis, IL, Arnold, N, Belotti, M, Borg, A, Buecher, B, Buys, SS, Caputo, SM, Chung, WK, Colas, C, Colonna, S, Cook, J, Daly, MB, de la Hoya, M, de Pauw, A, Delhomelle, H, Eason, J, Engel, C, Evans, DG, Faust, U, Fehm, TN, Fostira, F, Fountzilas, G, Frone, M, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Gehrig, A, Glendon, G, Goldgar, DE, Golmard, L, Greene, MH, Hahnen, E, Hamann, U, Hanson, H, Hassan, T, Hentschel, J, Horvath, J, Izatt, L, Janavicius, R, Jiao, Y, John, EM, Karlan, BY, Kim, S-W, Konstantopoulou, I, Kwong, A, Lauge, A, Lee, JW, Lesueur, F, Mebirouk, N, Meindl, A, Mouret-Fourme, E, Musgrave, H, Yie, JNY, Niederacher, D, Park, SK, Pedersen, IS, Ramser, J, Ramus, SJ, Rantala, J, Rashid, MU, Reichl, F, Ritter, J, Rump, A, Santamarina, M, Saule, C, Schmidt, G, Schmutzler, RK, Senter, L, Shariff, S, Singer, CF, Southey, MC, Stoppa-Lyonnet, D, Sutter, C, Tan, Y, Teo, SH, Terry, MB, Thomassen, M, Tischkowitz, M, Toland, AE, Torres, D, Vega, A, Wagner, SA, Wang-Gohrke, S, Wappenschmidt, B, Weber, BHF, Yannoukakos, D, Spurdle, AB, Easton, DF, Chenevix-Trench, G, Ottini, L, Antoniou, AC, Li, S, Silvestri, V, Leslie, G, Rebbeck, TR, Neuhausen, SL, Hopper, JL, Nielsen, HR, Lee, A, Yang, X, McGuffog, L, Parsons, MT, Andrulis, IL, Arnold, N, Belotti, M, Borg, A, Buecher, B, Buys, SS, Caputo, SM, Chung, WK, Colas, C, Colonna, S, Cook, J, Daly, MB, de la Hoya, M, de Pauw, A, Delhomelle, H, Eason, J, Engel, C, Evans, DG, Faust, U, Fehm, TN, Fostira, F, Fountzilas, G, Frone, M, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Gehrig, A, Glendon, G, Goldgar, DE, Golmard, L, Greene, MH, Hahnen, E, Hamann, U, Hanson, H, Hassan, T, Hentschel, J, Horvath, J, Izatt, L, Janavicius, R, Jiao, Y, John, EM, Karlan, BY, Kim, S-W, Konstantopoulou, I, Kwong, A, Lauge, A, Lee, JW, Lesueur, F, Mebirouk, N, Meindl, A, Mouret-Fourme, E, Musgrave, H, Yie, JNY, Niederacher, D, Park, SK, Pedersen, IS, Ramser, J, Ramus, SJ, Rantala, J, Rashid, MU, Reichl, F, Ritter, J, Rump, A, Santamarina, M, Saule, C, Schmidt, G, Schmutzler, RK, Senter, L, Shariff, S, Singer, CF, Southey, MC, Stoppa-Lyonnet, D, Sutter, C, Tan, Y, Teo, SH, Terry, MB, Thomassen, M, Tischkowitz, M, Toland, AE, Torres, D, Vega, A, Wagner, SA, Wang-Gohrke, S, Wappenschmidt, B, Weber, BHF, Yannoukakos, D, Spurdle, AB, Easton, DF, Chenevix-Trench, G, Ottini, L, and Antoniou, AC

Abstract

PURPOSE: To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS: We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS: BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION: In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.

Published
2022

28. Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome

Author

Tischkowitz, M, Colas, C, Pouwels, S, Hoogerbrugge, N, Ligtenberg, M, Oostenbrink, Rianne, Sijmons, R, Evans, G, Woodward, E, Peltonen, S, Hietala, M, and Pediatrics

Subjects
PTEN, medicine.medical_specialty, Colorectal cancer, Consensus Development Conferences as Topic, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Population, MEDLINE, CHILDREN, Article, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Medicine and Health Sciences, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Genetics, Humans, Medicine, Genetic Testing, education, Intensive care medicine, Cancer genetics, Early Detection of Cancer, Genetics (clinical), 030304 developmental biology, Preventive medicine, 0303 health sciences, education.field_of_study, biology, business.industry, Endometrial cancer, Cancer, Guideline, medicine.disease, RISKS, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 030220 oncology & carcinogenesis, Practice Guidelines as Topic, biology.protein, Medical genetics, Hamartoma Syndrome, Multiple, business
Abstract

Contains fulltext : 225252.pdf (Publisher’s version ) (Open Access) PTEN hamartoma tumour syndrome is a diverse multi-system disorder predisposing to the development of hamartomatous growths, increasing risk of breast, thyroid, renal cancer, and possibly increasing risk of endometrial cancer, colorectal cancer and melanoma. There is no international consensus on cancer surveillance in PHTS and all current guidelines are based on expert opinion. A comprehensive literature review was undertaken and guidelines were developed by clinicians with expertise from clinical genetics, gynaecology, endocrinology, dermatology, radiology, gastroenterology and general surgery, together with affected individuals and their representatives. Recommendations were put forward for surveillance for breast, thyroid and renal cancers. Limited recommendations were developed for other sites including endometrial, colon and skin. The proposed cancer surveillance recommendations for PHTS require a coordinated multidisciplinary approach and significant patient commitment. The evidence base for cancer surveillance in this guideline are limited, emphasising the need for prospective evaluation of the effectiveness of surveillance in the PHTS population.

Published
2020

33. Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort

Author

Lavoine, N, Colas, C, Muleris, M, Bodo, S, Duval, A, Entz-Werle, N, Coulet, F, Cabaret, O, Andreiuolo, F, Charpy, C, Sebille, G, Wang, Q, Lejeune, S, Buisine, M P, Leroux, D, Couillault, G, Leverger, G, Fricker, J P, Guimbaud, R, Mathieu-Dramard, M, Jedraszak, G, Cohen-Hagenauer, O, Guerrini-Rousseau, L, Bourdeaut, F, Grill, J, Caron, O, Baert-Dusermont, S, Tinat, J, Bougeard, G, Frébourg, T, and Brugières, L

Published
2015
Full Text
View/download PDF

35. Grounding Language to Autonomously-Acquired Skills via Goal Generation

Author

Akakzia, Ahmed, Colas, C��dric, Oudeyer, Pierre-Yves, Chetouani, Mohamed, Sigaud, Olivier, Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Flowing Epigenetic Robots and Systems (Flowers), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Perception, Interaction, Robotique sociales (PIROS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Unité d'Informatique et d'Ingénierie des Systèmes (U2IS), and École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École Nationale Supérieure de Techniques Avancées (ENSTA Paris)

Subjects
FOS: Computer and information sciences, Computer Science - Machine Learning, Artificial intelligence and robotics, Artificial Intelligence (cs.AI), [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Computer Science - Artificial Intelligence, Statistics - Machine Learning, Reinforcement learning, Machine Learning (stat.ML), Machine Learning (cs.LG), [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract

We are interested in the autonomous acquisition of repertoires of skills. Language-conditioned reinforcement learning (LC-RL) approaches are great tools in this quest, as they allow to express abstract goals as sets of constraints on the states. However, most LC-RL agents are not autonomous and cannot learn without external instructions and feedback. Besides, their direct language condition cannot account for the goal-directed behavior of pre-verbal infants and strongly limits the expression of behavioral diversity for a given language input. To resolve these issues, we propose a new conceptual approach to language-conditioned RL: the Language-Goal-Behavior architecture (LGB). LGB decouples skill learning and language grounding via an intermediate semantic representation of the world. To showcase the properties of LGB, we present a specific implementation called DECSTR. DECSTR is an intrinsically motivated learning agent endowed with an innate semantic representation describing spatial relations between physical objects. In a first stage (G -> B), it freely explores its environment and targets self-generated semantic configurations. In a second stage (L -> G), it trains a language-conditioned goal generator to generate semantic goals that match the constraints expressed in language-based inputs. We showcase the additional properties of LGB w.r.t. both an end-to-end LC-RL approach and a similar approach leveraging non-semantic, continuous intermediate representations. Intermediate semantic representations help satisfy language commands in a diversity of ways, enable strategy switching after a failure and facilitate language grounding., Published at ICLR 2021

Published
2021

38. Development of a Tool to Measure the Clinical Response to Biologic Therapy in Uncontrolled Severe Asthma: The FEV1, Exacerbations, Oral Corticosteroids, Symptoms Score

Author

de Llano L, Davila I, Martinez-Moragon E, Dominguez-Ortega J, Almonacid C, Colas C, Garcia-Rivero J, Carmona L, de Yebenes M, and Cosio B

Subjects
Severe asthma, Asthma management, Monoclonal anti-bodies, Asthma
Abstract

BACKGROUND: There is a lack of tools to quantify the response to monoclonal antibodies (mAbs) holistically in severe uncontrolled asthma patients. OBJECTIVE: To develop a valid score to assist specialists in this clinical context. METHODS: The score was developed in four subsequent phases: (1) elaboration of the theoretical model of the construct intended to be measured (response to mAbs); (2) definition and selection of items and measurement instruments by Delphi survey; (3) weight assignment of the selected items by multicriteria decision analysis using the Potentially All Pairwise RanKings of All Possible Alternatives methodology using the 1000minds software; and (4) face validity assessment of the obtained score. RESULTS: Four core items, with different levels of response for each, were selected: severe exacerbations, oral corticosteroid use, symptoms (evaluated by Asthma Control Test), and bronchial obstruction (assessed by FEV1 percent predicted). Severe exacerbations and oral corticosteroid maintenance dose were weighted most heavily (38% each), followed by symptoms (13%) and FEV1 (11%). Higher scores in the weighted system indicate a better response and the range of responses runs from 0 (worsening) to 100 (best possible response). Face validity was high (intraclass correlation coefficient of 0.86). CONCLUSIONS: The FEV1, exacerbations, oral corticosteroids, symptoms score allows clinicians to quantify response in severe uncontrolled asthma patients who are being treated with mAbs.(c) 2021 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2021;9:2725-31)

Published
2021

39. GENOTYPE-PHENOTYPE ASSOCIATIONS PROVIDE A RATIONAL TO IDENTIFY POTENTIALLY ACTIONABLE VUS

Author

Pelaez J, Monteiro R, Lobo S, Sousa L, Pinheiro H, Castedo S, Garrido L, Teixeira M, Michils G, Bours V, de Putter R, Golmard L, Blanluet M, Colas C, Benusiglio P, Desseignes C, Florence C, Aretz S, Spier I, Huneburg R, Gieldon L, Schrock E, Holinski-Feder E, Steinke V, Calistri D, Tedaldi G, Ranzani G, Genuardi M, Silveira C, Silva I, Krajc M, Blatnik A, Novacovik S, Patino-Garcia A, Soto J, Lazaro C, Capella G, Brunet-Vidal J, Balmana J, Dominguez-Garrido E, Ligtenberg M, Fewings E, Fitzgerald R, Woodward E, Evans G, Hanson H, Lagerstedt-Robinson K, Bajalica-Lagercrantz S, Egas C, Tejada M, Dahan K, Feret D, Hoogerbrugge N, Tischkowitz M, and Oliveira C

Published
2021

40. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author

Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), Antoniou, A.C. (Antonis C.), Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), and Antoniou, A.C. (Antonis C.)

Abstract

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.

Published
2021
Full Text
View/download PDF

41. Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers (Nature Communications, (2021), 12, 1, (1078), 10.1038/s41467-020-20496-3).

Author

Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., and Antoniou A.C.

Abstract

The original version of this Article contained an error in the spelling of the author Heiko Becher, which was incorrectly given as Heko Becher. This has now been corrected in both the PDF and HTML versions of the Article.Copyright © 2021, The Author(s).

Published
2021

42. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.

Author

Gesta P., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Niederacher D., Nielsen F.C., Nikitina-Zake L., Nogues C., Olah E., Olopade O.I., Ong K.-R., O'Shaughnessy-Kirwan A., Osorio A., Ott C.-E., Papi L., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Peterlongo P., Pfeiler G., Phillips K.-A., Prajzendanc K., Pujana M.A., Radice P., Ramser J., Ramus S.J., Rantala J., Rennert G., Risch H.A., Robson M., Ronlund K., Salani R., Schuster H., Senter L., Shah P.D., Sharma P., Side L.E., Singer C.F., Slavin T.P., Soucy P., Southey M.C., Spurdle A.B., Steinemann D., Steinsnyder Z., Stoppa-Lyonnet D., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thull D.L., Tischkowitz M., Tognazzo S., Toland A.E., Trainer A.H., Tung N., van Engelen K., van Rensburg E.J., Vega A., Vierstraete J., Wagner G., Walker L., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Yadav S., Yang X., Yannoukakos D., Zimbalatti D., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Antoniou A.C., GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators, HEBON Investigators, GENEPSO Investigators, Barnes D.R., Rookus M.A., McGuffog L., Leslie G., Mooij T.M., Dennis J., Mavaddat N., Aittomaki K., Andrulis I.L., Arnold N., Arun B.K., Azzollini J., Balmana J., Barkardottir R.B., Benitez J., Bialkowska K., Blanco A.M., Blok M.J., Bonanni B., Boonen S.E., Borg A., Bozsik A., Bradbury A.R., Brunet J., Buys S.S., Caldes T., Caligo M.A., Campbell I., Christensen L.L., Chung W.K., Claes K.B.M., Berthet P., Colas C., Adlard J., Ahmed M., Antoniou A., Barrowdale D., Brennan P., Brewer C., Easton D., Evans D.G., Side L., Collonge-Rame M.-A., Cook J., Daly M.B., Davidson R., de la Hoya M., de Putter R., Delnatte C., Diez O., Ding Y.C., Domchek S.M., Dorfling C.M., Dumont M., Eeles R., Ejlertsen B., Engel C., Faivre L., Foretova L., Fostira F., Friedlander M., Friedman E., Frost D., Ganz P.A., Garber J., Gehrig A., Gerdes A.-M., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gschwantler-Kaulich D., Hahnen E., Hamann U., Hanson H., Hentschel J., Hogervorst F.B.L., Hooning M.J., Horvath J., Hu C., Hulick P.J., Imyanitov E.N., Chenevix-Trench G., Spurdle A., Blok M., Devilee P., Hogervorst F., Hooning M., Mensenkamp A., Meijers-Heijboer H., Rookus M., Engelen K., Andrieu 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., Lazaro C., Lester J., Lesueur F., Liljegren A., Loud J.T., Lubinski J., Mai P.L., Manoukian S., Mari V., Mebirouk N., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller A., Montagna M., Mouret-Fourme E., Mukherjee S., Gesta P., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Niederacher D., Nielsen F.C., Nikitina-Zake L., Nogues C., Olah E., Olopade O.I., Ong K.-R., O'Shaughnessy-Kirwan A., Osorio A., Ott C.-E., Papi L., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Peterlongo P., Pfeiler G., Phillips K.-A., Prajzendanc K., Pujana M.A., Radice P., Ramser J., Ramus S.J., Rantala J., Rennert G., Risch H.A., Robson M., Ronlund K., Salani R., Schuster H., Senter L., Shah P.D., Sharma P., Side L.E., Singer C.F., Slavin T.P., Soucy P., Southey M.C., Spurdle A.B., Steinemann D., Steinsnyder Z., Stoppa-Lyonnet D., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thull D.L., Tischkowitz M., Tognazzo S., Toland A.E., Trainer A.H., Tung N., van Engelen K., van Rensburg E.J., Vega A., Vierstraete J., Wagner G., Walker L., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Yadav S., Yang X., Yannoukakos D., Zimbalatti D., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Antoniou A.C., GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators, HEBON Investigators, GENEPSO Investigators, Barnes D.R., Rookus M.A., McGuffog L., Leslie G., Mooij T.M., Dennis J., Mavaddat N., Aittomaki K., Andrulis I.L., Arnold N., Arun B.K., Azzollini J., Balmana J., Barkardottir R.B., Benitez J., Bialkowska K., Blanco A.M., Blok M.J., Bonanni B., Boonen S.E., Borg A., Bozsik A., Bradbury A.R., Brunet J., Buys S.S., Caldes T., Caligo M.A., Campbell I., Christensen L.L., Chung W.K., Claes K.B.M., Berthet P., Colas C., Adlard J., Ahmed M., Antoniou A., Barrowdale D., Brennan P., Brewer C., Easton D., Evans D.G., Side L., Collonge-Rame M.-A., Cook J., Daly M.B., Davidson R., de la Hoya M., de Putter R., Delnatte C., Diez O., Ding Y.C., Domchek S.M., Dorfling C.M., Dumont M., Eeles R., Ejlertsen B., Engel C., Faivre L., Foretova L., Fostira F., Friedlander M., Friedman E., Frost D., Ganz P.A., Garber J., Gehrig A., Gerdes A.-M., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gschwantler-Kaulich D., Hahnen E., Hamann U., Hanson H., Hentschel J., Hogervorst F.B.L., Hooning M.J., Horvath J., Hu C., Hulick P.J., Imyanitov E.N., Chenevix-Trench G., Spurdle A., Blok M., Devilee P., Hogervorst F., Hooning M., Mensenkamp A., Meijers-Heijboer H., Rookus M., Engelen K., Andrieu 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., Lazaro C., Lester J., Lesueur F., Liljegren A., Loud J.T., Lubinski J., Mai P.L., Manoukian S., Mari V., Mebirouk N., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller A., Montagna M., Mouret-Fourme E., and Mukherjee S.

Abstract

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. Method(s): 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. Result(s): 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 = 3x10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7x10-50). 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 = 3x10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4x10-12) carriers. The associations in the prospective cohort were similar. Conclusion(s): 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.Copyright © 2020, The Author(s).

Published
2021

43. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Author

Radice P., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R.L., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Radice P., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R.L., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Rantala J., Rashid M.U., Rennert G., Rennert H.S., and Robson M.

Abstract

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.Copyright © 2021, The Author(s).

Published
2021

44. Recommendations to improve identification of hereditary and familial colorectal cancer in Europe

Author

Vasen, H. F. A., Möslein, G., Alonso, A., Aretz, S., Bernstein, I., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Engel, C., Frayling, I., Rahner, N., Hes, F. J., Hodgson, S., Mecklin, J.-P., Møller, P., Myrhøj, T., Nagengast, F. M., Parc, Y., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J. R., Stormorken, A., Tejpar, S., Thomas, H. J. W., Wijnen, J., Lubinski, J., Järvinen, H., Claes, E., Heinimann, K., Karagiannis, J. A., Lindblom, A., Dove-Edwin, I., and Müller, H.

Published
2010
Full Text
View/download PDF

45. Peutz-Jeghers syndrome: a systematic review and recommendations for management

Author

Beggs, A.D., Latchford, A.R., Vasen, H.F.A., Moslein, G., Alonso, A., Aretz, S., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Friedl, W., Moller, P., Hes, F.J., Jarvinen, H., Mecklin, J.-P., Nagengast, F.M., Parc, Y., Phillips, R.K.S., Hyer, W., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J.W., Wijnen, J.T., Clark, S.K., and Hodgson, S.V.

Subjects
Peutz-Jeghers syndrome -- Diagnosis, Peutz-Jeghers syndrome -- Care and treatment, Peutz-Jeghers syndrome -- Development and progression, Peutz-Jeghers syndrome -- Risk factors, Medical literature -- Analysis, Health
Published
2010

47. Guidelines for the clinical management of familial adenomatous polyposis (FAP)

Author

Vasen, H.F.A., Moslein, G., Alonso, A., Aretz, S., Bernstein, I., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Engel, C., Frayling, I., Friedl, W., Hes, F.J., Hodgson, S., Jarvinen, H., Mecklin, J.-P., Moller, P., Myrhoi, T., Nagengast, F.M., Parc, Y., Phillips, R., Clark, S.K., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J.W., and Wijnen, J.

Subjects
Polyposis, Familial -- Care and treatment, Practice guidelines (Medicine) -- Evaluation, Colorectal cancer -- Risk factors, Colorectal cancer -- Prevention, Health
Published
2008

48. Language-Conditioned Goal Generation: a New Approach to Language Grounding for RL

Author

Colas, C��dric, Akakzia, Ahmed, Oudeyer, Pierre-Yves, Chetouani, Mohamed, and Sigaud, Olivier

Subjects
FOS: Computer and information sciences, Computer Science - Machine Learning, Artificial Intelligence (cs.AI), Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Statistics - Machine Learning, Machine Learning (stat.ML), Computation and Language (cs.CL), Machine Learning (cs.LG)
Abstract

In the real world, linguistic agents are also embodied agents: they perceive and act in the physical world. The notion of Language Grounding questions the interactions between language and embodiment: how do learning agents connect or ground linguistic representations to the physical world ? This question has recently been approached by the Reinforcement Learning community under the framework of instruction-following agents. In these agents, behavioral policies or reward functions are conditioned on the embedding of an instruction expressed in natural language. This paper proposes another approach: using language to condition goal generators. Given any goal-conditioned policy, one could train a language-conditioned goal generator to generate language-agnostic goals for the agent. This method allows to decouple sensorimotor learning from language acquisition and enable agents to demonstrate a diversity of behaviors for any given instruction. We propose a particular instantiation of this approach and demonstrate its benefits.

Published
2020

49. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Author

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

Subjects
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).

Published
2020

50. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers

Author

Mavaddat, N., Antoniou, A.C., Mooij, T.M., Hooning, M.J., Heemskerk-Gerritsen, B.A., Nogues, C., Laborde, L., Breysse, E., Stoppa-Lyonnet, D., Gauthier-Villars, M., Buecher, B., Caron, O., Fourme-Mouret, E., Fricker, J.P., Lasset, C., Bonadona, V., Berthet, P., Faivre, L., Luporsi, E., Mari, V., Gladieff, L., Gesta, P., Sobol, H., Eisinger, F., Longy, M., Dugast, C., Colas, C., Coupier, I., Pujol, P., Corsini, C., Lortholary, A., Vennin, P., Adenis, C., Nguyen, T.D., Delnatte, C., Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Bignon, Y.J., Demange, L., Penet, C., Dreyfus, H., Cohen-Haguenauer, O., Venat-Bouvet, L., Leroux, D., Zattara-Cannoni, H., Fert-Ferrer, S., Bera, O., Ellis, S., Barrowdale, D., Frost, D., Evans, D.G., Izatt, L., Adlard, J., Eeles, R., Brewer, C., Tischkowitz, M., Henderson, A., Cook, J., Eccles, D., Hogervorst, F.B.L., Collee, J.M., Asperen, C.J. van, Mensenkamp, A.R., Ausems, M.G.E.M., Meijers-Heijboer, H.E.J., Engelen, K. van, Blok, M.J., Oosterwijk, J.C., Verloop, J., Broek, E. van den, Mourits, M.J.E., Koppert, L.B., Hopper, J.L., John, E.M., Chung, W.K., Andrulis, I.L., Daly, M.B., Buys, S.S., Benitez, J., Caldes, T., Jakubowska, A., Simard, J., Singer, C.F., Tan, Y., Olah, E., Navratilova, M., Foretova, L., Gerdes, A.M., Roos-Blom, M.J., Leeuwen, F.E. van, Arver, B., Olsson, H., Schmutzler, R.K., Engel, C., Kast, K., Phillips, K.A., Terry, M.B., Milne, R.L., Goldgar, D.E., Rookus, M.A., Andrieu, N., Easton, D.F., GENEPSO, EMBRACE, HEBON, kConFab Investigators, IBCCS, kConFab, BCFR, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Erasmus MC Cancer Institute, Rotterdam, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Catherine-de-Sienne [Nantes] (CCS), Manchester University NHS Foundation Trust (MFT), Guy's & St Thomas' NHS Foundation Trust, Chapel Allerton Hospital, University of Leeds, Royal Marsden NHS Foundation Trust, Royal Devon & Exeter Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Wessex clinical genetics service, Vrije Universiteit Amsterdam [Amsterdam] (VU), University Medical Center Groningen [Groningen] (UMCG), Department of Medical Genetics, University Medical Center [Utrecht], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Department of Epidemiology, Cancer Prevention Institute of California, Columbia University [New York], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Division of Population Science, Fox Chase Cancer Center, Department of Internal Medicine, Huntsman Cancer Institute, Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Medizinische Universität Wien = Medical University of Vienna, National Institute of Oncology, Masaryk Memorial Cancer Institute (MMCI), Masaryk University [Brno] (MUNI), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, The Netherlands Cancer Institute [Amsterdam, The Netherlands], Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Cancer Epidemiology Centre, Cancer Council Victoria, International Agency for Cancer Research (IACR), Netherlands Cancer Institute, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Andrieu, Nadine, Human genetics, Epidemiology and Data Science, Mavaddat, Nasim [0000-0003-0307-055X], Eeles, Ros [0000-0002-3698-6241], Engel, Christoph [0000-0002-7247-282X], Apollo - University of Cambridge Repository, Pomeranian Medical University-International Hereditary Cancer Centre, Masaryk Memorial Cancer Institute (RECAMO), Columbia Mailman School of Public Health-Columbia University [New York], Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Antoniou, Antonis [0000-0001-9223-3116], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Medical Oncology, Surgery, Cancer Research UK (Reino Unido), NIH - National Cancer Institute (NCI) (Estados Unidos), United States Department of Health and Human Services, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea. European Research Council (ERC), Norwegian EEA Financial Mechanism, Hungarian Scientific Research Fund (Hungría), Ministry of Education, Youth and Sports (República Checa), MH CZ -DRO (MMCI), National Health and Medical Research Council (Australia), Australian National Breast Cancer Foundation, Cancer Australia, ERA-NET TRANSAN JTC 2012 Cancer, Transcan grant, Biotechnology and Biological Sciences Research Council (Reino Unido), Pink Ribbons Project, Netherlands Organisation of Scientific Research, Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Deutsche Krebshilfe, National Institute for Health Research (Reino Unido), Unión Europea. Comisión Europea. 7 Programa Marco, Ministry of Economic Development, Innovation and Export Trade-grant, Canadian Institutes of Health Research, Cancer Research UK, NIH National Cancer Institute (NCI), United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Ministerio de Economia y Competividad (MINECO), European Research Council (ERC), Hungarian Research Grants, MEYS -NPS I, National Health and Medical Research Council of Australia, BBMRI grant, Pink Ribbon grants, Netherlands Organisation of Scientific Research grant, KWF Kankerbestrijding, Instituto de Salud Carlos III - ISCIII, National Institute for Health Research (NIHR), European Union Seventh Framework Program (2007-2013), Canadian Institutes of Health Research (CIHR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), United States of Department of Health & Human Services, European Research Council, APH - Quality of Care, APH - Methodology, Graduate School, ARD - Amsterdam Reproduction and Development, RS: GROW - R4 - Reproductive and Perinatal Medicine, and MUMC+: DA KG Lab Centraal Lab (9)

Subjects
endocrine system diseases, SURGERY, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Cohort Studies, 0302 clinical medicine, BRCA2 Mutation, Breast cancer, Surgical oncology, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Salpingo-oophorectomy/methods, 0303 health sciences, Natural menopause, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Obstetrics, BRCA1 Protein, Breast Neoplasms/epidemiology, Incidence (epidemiology), Incidence, WOMEN, ASSOCIATION, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, OVARIAN, BRCA2 Protein/genetics, 3. Good health, Menopause, Risk-reducing salpingo-oophorectomy, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SURVIVAL, Female, Research Article, Cohort study, Adult, medicine.medical_specialty, Salpingo-oophorectomy, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, lcsh:RC254-282, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, METAANALYSIS, 030304 developmental biology, BRCA2 Protein, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, CONSORTIUM, risk-reducing salpingo-oophorectomy, International Agencies, medicine.disease, BRCA1, BRCA2, KCONFAB, REDUCTION, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, LINK, Mutation, BRCA1 Protein/genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Risk Reduction Behavior
Abstract

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare Diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. INHERIT was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program-grant #CRN-87521-and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie, de la Science et de l' Innovation du Quebec through Genome Quebec, and The Quebec Breast Cancer Foundation. Jacques Simard is a Chairholder of the Canada Research Chair in Oncogenetics. EMBRACE is supported by the Cancer Research UK grants C1287/A23382 and C1287/A16563. D. Gareth Evans is supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by the Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/A11174. MT is funded by the European Union Seventh Framework Program (2007-2013)/European Research Council (310018). The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 110837, Rita K. Schmutzler). The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, no. 2014-008). HCSC was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12-054. The IHCC was supported by Grant PBZ_ KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/2014). This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the National Institute of Health U.S.A. (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation fellow. MODSQUAD-Czech Republic, Brno, was supported by MH CZ -DRO (MMCI, 00209805) and by MEYS -NPS I -LO1413 to LF and MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228, and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Sí

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results