136 results on '"Durda K"'
Search Results
2. Selenium and genotypes as marker of risk in BRCA1 mutation carriers
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Jaworska K, Jakubowska A, Huzarski T, Durda K, Serrano-Fernandez P, Sukiennicki G, Muszyńska M, Byrski T, Gronwald J, Gupta S, and Lubiński J J
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
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- View/download PDF
3. Prospective observation of breast/ovarian cancer risk in BRCA1 carriers depending on serum selenium level optimized with diet
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Lubiński J, Huzarski T, Jakubowska A, Gronwald J, Jaworska K, Muszyńska M, Sukiennicki G, Durda K, Cybulski C, Dębniak T, Tołoczko A, Oszurek O, Serrano-Fernandez P, Scott R, and Narod S
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
- Full Text
- View/download PDF
4. Rapid test for detection of high risk of breast cancer
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Durda K, Jaworska K, Jakubowska A, Dębniak T, and Górski B
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
- Full Text
- View/download PDF
5. Identification of new genes associated with breast and ovarian cancer risk. Advances of BCAC, CIMBA and OCAC
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Jakubowska A, Gronwald J, Jaworska K, and Durda K
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2011
- Full Text
- View/download PDF
6. Selenium and the risk of cancer in BRCA1 carriers
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Lubinski J, Jaworska K, Durda K, Jakubowska A, Huzarski T, Byrski T, Stawicka M, Gronwald J, Górski B, Wasowicz W, Kilar E, Szwiec M, Surdyka D, Marczyk E, Sun P, and Narod SA
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2011
- Full Text
- View/download PDF
7. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
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Antoniou, AC, Kuchenbaecker, KB, Soucy, P, Beesley, J, Chen, X, McGuffog, L, Lee, A, Barrowdale, D, Healey, S, Sinilnikova, OM, Caligo, MA, Loman, N, Harbst, K, Lindblom, A, Arver, B, Rosenquist, R, Karlsson, P, Nathanson, K, Domchek, S, Rebbeck, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Zlowowcka-Perlowska, E, Osorio, A, Duran, M, Andres, R, Benitez, J, Hamann, U, Hogervorst, FB, van Os, TA, Verhoef, S, Meijers-Heijboer, HEJ, Wijnen, J, Garcia, EBG, Ligtenberg, MJ, Kriege, M, Collee, M, Ausems, MGEM, Oosterwijk, JC, Peock, S, Frost, D, Ellis, SD, Platte, R, Fineberg, E, Evans, DG, Lalloo, F, Jacobs, C, Eeles, R, Adlard, J, Davidson, R, Cole, T, Cook, J, Paterson, J, Douglas, F, Brewer, C, Hodgson, S, Morrison, PJ, Walker, L, Rogers, MT, Donaldson, A, Dorkins, H, Godwin, AK, Bove, B, Stoppa-Lyonnet, D, Houdayer, C, Buecher, B, de Pauw, A, Mazoyer, S, Calender, A, Leone, M, Bressac-de Paillerets, B, Caron, O, Sobol, H, Frenay, M, Prieur, F, Ferrer, SF, Mortemousque, I, Buys, S, Daly, M, Miron, A, Terry, MB, Hopper, JL, John, EM, Southey, M, Goldgar, D, Singer, CF, Fink-Retter, A, Tea, M-K, Kaulich, DG, Hansen, TVO, Nielsen, FC, Barkardottir, RB, Gaudet, M, Kirchhoff, T, Joseph, V, Dutra-Clarke, A, Offit, K, and Piedmonte, M
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- 2012
8. The beneficial reuse of contaminated sediment: Long-term assessment of fly ash and lime-based mixtures
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Dunja Rađenović, Đurđa Kerkez, Dragana Tomašević Pilipović, Miloš Dubovina, Miloš Šešlija, Slaven Tenodi, and Igor Peško
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Sediment management ,Solidification/stabilization ,Long-term ageing ,Leaching ,Structural properties ,Treatment economy ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
In recent decades, sediment has been recognised as a problematic resource due to its potentially harmful effects and the large quantities present in water bodies. There is a need to properly manage large quantities of dredged sediments so that they can be used as a resource and not necessarily treated as a waste product. This research investigates the effects of ageing and maturation of solidified/stabilized mixtures of contaminated sediment with fly ash and lime. The effects of ageing on the microstructural properties and chemical integrity of mixtures were studied for 7 days, 28 days, and 7 years using scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS), X-ray diffraction analysis (XRD), and DIN (German Standard Procedure for Water, Wastewater and Sediment Testing (Group S)) and TCLP (Toxicity Characteristic Leaching Procedure) leaching tests. The results of the microstructure and strength analysis showed that the use of fly ash and lime as binders promoted the permanent structural integrity of the sediment. The treated sediment with 20 wt% fly ash and 10 wt% lime (F20L10) achieved higher overall strength compared to the mixture containing only 30 wt% fly ash (F30). The speciation and redistribution of metals and As in the treated sediment mixtures during the long-term evaluation indicate a strong reduction in their mobility. This material can be considered environmentally friendly and can be used as a fill material in road construction. The investment and operating costs are justified in this solution for sediment management. However, it is important to monitor the produced material over time to ensure that it remains effective and sustainable in the long term.
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- 2024
- Full Text
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9. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
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Figlioli, G, Bogliolo, M, Catucci, I, Caleca, L, Lasheras, SV, Pujol, R, Kiiski, JI, Muranen, TA, Barnes, DR, Dennis, J, Michailidou, K, Bolla, MK, Leslie, G, Aalfs, CM, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Adank, MA, Adlard, J, Agata, S, Cadoo, K, Agnarsson, BA, Ahearn, T, Aittomäki, K, Ambrosone, CB, Andrews, L, Anton-Culver, H, Antonenkova, NN, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Asseryanis, E, Auber, B, Auvinen, P, Azzollini, J, Balmaña, J, Barkardottir, RB, Barrowdale, D, Barwell, J, Beane Freeman, LE, Beauparlant, CJ, Beckmann, MW, Behrens, S, Benitez, J, Berger, R, Bermisheva, M, Blanco, AM, Blomqvist, C, Bogdanova, NV, Bojesen, A, Bojesen, SE, Bonanni, B, Borg, A, Brady, AF, Brauch, H, Brenner, H, Brüning, T, Burwinkel, B, Buys, SS, Caldés, T, Caliebe, A, Caligo, MA, Campa, D, Campbell, IG, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Claes, KBM, Clarke, CL, Collavoli, A, Conner, TA, Cox, DG, Cybulski, C, Czene, K, Daly, MB, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dite, GS, Ditsch, N, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, and Durda, K
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nutritional and metabolic diseases ,skin and connective tissue diseases - Abstract
© 2019, The Author(s). Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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- 2019
10. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- Author
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Figlioli, G., Bogliolo, M., Catucci, I., Caleca, L., Lasheras, S. V., Pujol, R., Kiiski, J. I., Muranen, T. A., Barnes, D. R., Dennis, J., Michailidou, K., Bolla, M. K., Leslie, G., Aalfs, C. M., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C. S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Adank, M. A., Adlard, J., Agata, S., Cadoo, K., Agnarsson, B. A., Ahearn, T., Aittomaki, K., Ambrosone, C. B., Andrews, L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Arnold, N., Aronson, K. J., Arun, B. K., Asseryanis, E., Auber, B., Auvinen, P., Azzollini, J., Balmana, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., Beane Freeman, L. E., Beauparlant, C. J., Beckmann, M. W., Behrens, S., Benitez, J., Berger, R., Bermisheva, M., Blanco, A. M., Blomqvist, C., Bogdanova, N. V., Bojesen, A., Bojesen, S. E., Bonanni, B., Borg, A., Brady, A. F., Brauch, H., Brenner, H., Bruning, T., Burwinkel, B., Buys, S. S., Caldes, T., Caliebe, A., Caligo, M. A., Campa, D., Campbell, I. G., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Claes, K. B. M., Clarke, C. L., Collavoli, A., Conner, T. A., Cox, D. G., Cybulski, C., Czene, K., Daly, M. B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y. C., Dite, G. S., Ditsch, N., Domchek, S. M., Dorfling, C. M., dos-Santos-Silva, I., Durda, K., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Ellberg, C., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Flyger, H., Foulkes, W. D., Friebel, T. M., Friedman, E., Gabrielson, M., Gaddam, P., Gago-Dominguez, M., Gao, C., Gapstur, S. M., Garber, J., Garcia-Closas, M., Garcia-Saenz, J. A., Gaudet, M. M., Gayther, S. A., Belotti, M., Bertrand, O., Birot, A. -M., Buecher, B., Caputo, S., Dupre, A., Fourme, E., Gauthier-Villars, M., Golmard, L., Le Mentec, M., Moncoutier, V., de Pauw, A., Saule, C., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Bressac-de-Paillerets, B., Caron, O., Guillaud-Bataille, M., Bignon, Y. -J., Uhrhammer, N., Bonadona, V., Lasset, C., Berthet, P., Castera, L., Vaur, D., Bourdon, V., Nogues, C., Noguchi, T., Popovici, C., Remenieras, A., Sobol, H., Coupier, I., Pujol, P., Adenis, C., Dumont, A., Revillion, F., Muller, D., Barouk-Simonet, E., Bonnet, F., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Guimbaud, R., Feillel, V., Toulas, C., Dreyfus, H., Leroux, C. D., Peysselon, M., Rebischung, C., Legrand, C., Baurand, A., Bertolone, G., Coron, F., Faivre, L., Jacquot, C., Lizard, S., Kientz, C., Lebrun, M., Prieur, F., Fert-Ferrer, S., Mari, V., Venat-Bouvet, L., Bezieau, S., Delnatte, C., Mortemousque, I., Colas, C., Coulet, F., Soubrier, F., Warcoin, M., Bronner, M., Sokolowska, J., Collonge-Rame, M. -A., Damette, A., Gesta, P., Lallaoui, H., Chiesa, J., Molina-Gomes, D., Ingster, O., Manouvrier-Hanu, S., Lejeune, S., Giles, G. G., Glendon, G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Guenel, P., Gutierrez-Barrera, A. M., Haeberle, L., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Harrington, P. A., Hein, A., Heyworth, J., Hillemanns, P., Hollestelle, A., Hopper, J. L., Hosgood, H. D., Howell, A., Hu, C., Hulick, P. J., Hunter, D. J., Imyanitov, E. N., Aghmesheh, M., Greening, S., Amor, D., Gattas, M., Botes, L., Buckley, M., Friedlander, M., Koehler, J., Meiser, B., Saleh, M., Salisbury, E., Trainer, A., Tucker, K., Antill, Y., Dobrovic, A., Fellows, A., Fox, S., Harris, M., Nightingale, S., Phillips, K., Sambrook, J., Thorne, H., Armitage, S., Arnold, L., Kefford, R., Kirk, J., Rickard, E., Bastick, P., Beesley, J., Hayward, N., Spurdle, A., Walker, L., Beilby, J., Saunders, C., Bennett, I., Blackburn, A., Bogwitz, M., Gaff, C., Lindeman, G., Pachter, N., Scott, C., Sexton, A., Visvader, J., Taylor, J., Winship, I., Brennan, M., Brown, M., French, J., Edwards, S., Burgess, M., Burke, J., Patterson, B., Butow, P., Culling, B., Caldon, L., Callen, D., Chauhan, D., Eisenbruch, M., Heiniger, L., Chauhan, M., Christian, A., Dixon, J., Kidd, A., Cohen, P., Colley, A., Fenton, G., Crook, A., Dickson, R., Field, M., Cui, J., Cummings, M., Dawson, S. -J., Defazio, A., Delatycki, M., Dudding, T., Edkins, T., Farshid, G., Flanagan, J., Fong, P., Forrest, L., Gallego-Ortega, D., George, P., Gill, G., Kollias, J., Haan, E., Hart, S., Jenkins, M., Hunt, C., Lakhani, S., Lipton, L., Lobb, L., Mann, G., Mclachlan, S. A., O'Connell, S., O'Sullivan, S., Pieper, E., Robinson, B., Saunus, J., Scott, E., Shelling, A., Williams, R., Young, M. A., Isaacs, C., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Karlan, B. Y., Khusnutdinova, E., Kitahara, C. M., Konstantopoulou, I., Koutros, S., Kraft, P., Lambrechts, D., Lazaro, C., Le Marchand, L., Lester, J., Lesueur, F., Lilyquist, J., Loud, J. T., K. H., Lu, Luben, R. N., Lubinski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martens, J. W. M., Maurer, T., Mavroudis, D., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Montagna, M., Nathanson, K. L., Neuhausen, S. L., Newman, W. G., Nguyen-Dumont, T., Nielsen, F. C., Nielsen, S., Nikitina-Zake, L., Offit, K., Olah, E., Olopade, O. I., Olshan, A. F., Olson, J. E., Olsson, H., Osorio, A., Ottini, L., Peissel, B., Peixoto, A., Peto, J., Plaseska-Karanfilska, D., Pocza, T., Presneau, N., Pujana, M. A., Punie, K., Rack, B., Rantala, J., Rashid, M. U., Rau-Murthy, R., Rennert, G., Lejbkowicz, F., Rhenius, V., Romero, A., Rookus, M. A., Ross, E. A., Rossing, M., Rudaitis, V., Ruebner, M., Saloustros, E., Sanden, K., Santamarina, M., Scheuner, M. T., Schmutzler, R. K., Schneider, M., Senter, L., Shah, M., Sharma, P., Shu, X. -O., Simard, J., Singer, C. F., Sohn, C., Soucy, P., Southey, M. C., Spinelli, J. J., Steele, L., Stoppa-Lyonnet, D., Tapper, W. J., Teixeira, M. R., Terry, M. B., Thomassen, M., Thompson, J., Thull, D. L., Tischkowitz, M., Tollenaar, R. A. E. M., Torres, D., Troester, M. A., Truong, T., Tung, N., Untch, M., Vachon, C. M., van Rensburg, E. J., van Veen, E. M., Vega, A., Viel, A., Wappenschmidt, B., Weitzel, J. N., Wendt, C., Wieme, G., Wolk, A., Yang, X. R., Zheng, W., Ziogas, A., Zorn, K. K., Dunning, A. M., Lush, M., Wang, Q., Mcguffog, L., Parsons, M. T., Pharoah, P. D. P., Fostira, F., Toland, A. E., Andrulis, I. L., Ramus, S. J., Swerdlow, A. J., Greene, M. H., Chung, W. K., Milne, R. L., Chenevix-Trench, G., Dork, T., Schmidt, M. K., Easton, D. F., Radice, P., Hahnen, E., Antoniou, A. C., Couch, F. J., Nevanlinna, H., Surralles, J., Peterlongo, P., Caleca, Laura [0000-0002-3381-7493], Muranen, Taru A. [0000-0002-5895-1808], Dennis, Joe [0000-0003-4591-1214], Adlard, Julian [0000-0002-1693-0435], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Devilee, Peter [0000-0002-8023-2009], Foulkes, William D. [0000-0001-7427-4651], Isaacs, Claudine [0000-0002-9646-1260], Jakimovska, Milena [0000-0002-1506-0669], Konstantopoulou, Irene [0000-0002-0470-0309], Lesueur, Fabienne [0000-0001-7404-4549], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Peto, Julian [0000-0002-1685-8912], Punie, Kevin [0000-0002-1162-7963], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Viel, Alessandra [0000-0003-2804-0840], Wieme, Greet [0000-0003-2718-5300], Zheng, Wei [0000-0003-1226-070X], Ziogas, Argyrios [0000-0003-4529-3727], Greene, Mark H. [0000-0003-1852-9239], Nevanlinna, Heli [0000-0002-0916-2976], Peterlongo, Paolo [0000-0001-6951-6855], Apollo - University of Cambridge Repository, Medical Oncology, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Yorkshire Regional Genetics Service, Department of Pathology, University Hospital and University of Iceland School of Medicine, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], University of Iceland [Reykjavik]-Landspitali - University Hospital, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Leicestershire Clinical Genetics Service, University Hospitals Leicester, Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Chaim Sheba Medical Center, Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Department of Oncology, Department of Obstetrics and Gynaecology (MHH), Hannover Medical School [Hannover] (MHH), Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, North West Thames Regional Genetics, Northwick Park Hospital, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Division of Clinical Epidemiology and Aging Research, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Molecular Epidemiology Research Group, Department of Internal Medicine, Huntsman Cancer Institute, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Cancer Epidemiology, Division of Cancer Epidemiology, Division of Cancer Epidemiology and Genetics, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Division of Population Science, Fox Chase Cancer Center, Department of Human Genetics & Department of Pathology, Leiden University Medical Center (LUMC), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Obstetrics and Gynecology [Munich, Germany], University-Hospital Munich-Großhadern [München]-Ludwig Maximilian University [Munich] (LMU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Wessex clinical genetics service, Lund University Hospital, Department of Genomic Medicine, University of Manchester [Manchester], Department of Breast Surgery, Herlev and Gentofte Hospital, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, National Institutes of Health [Bethesda] (NIH), Epidemiology Research Program, American Cancer Society, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Melbourne, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], International Agency for Cancer Research (IACR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Molecular Genetics of Breast Cancer, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, The Christie, Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Epidemiology, Cancer Prevention Institute of California, Unit of Nutrition and Cancer, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], National Center for Scientific Research 'Demokritos' (NCSR), Harvard School of Public Health, Laboratory for translational genetics Leuven, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, University of Hawai‘i [Mānoa] (UHM), 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), Clinical Genetics Branch, Strangeways Research Laboratory, Unit of Medical Genetics, Fondazione IRCCS INT, Department of Gynaecology and Obstetrics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Women's Health [London], University College London Hospitals (UCLH), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Department of Population Sciences, Beckman Research Institute of City of Hope, Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, University of Chicago, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Genetics Group, Spanish National Cancer Research Centre, Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Genetics, Portuguese Oncology Institute, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), University of Munich, Karolinska University Hospital [Stockholm], Umm Al-Qura University, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Netherlands Cancer Institute, IT University of Copenhagen (ITU), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Queen's University [Belfast] (QUB), Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University School of Medicine [Nashville], Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Odense University Hospital, Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), HELIOS Hospital Berlin-Buch, Cancer Genetics Laboratory, University of Pretoria [South Africa], Genomic Medicine Group, Universidade de Santiago de Compostela [Spain] (USC ), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of Science and Technology Beijing [Beijing] (USTB), University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Université de Pau et des Pays de l'Adour (UPPA), Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, The institute of cancer research [London], Department of Medical Genetics, Mayo Clinic, Cancer Epidemiology Centre, Cancer Council Victoria, Queensland Institute of Medical Research, Cancer Research U.K. Genetic Epidemiology Unit, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Department of Laboratory Medicine and Pathology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Muranen, Taru A [0000-0002-5895-1808], Foulkes, William D [0000-0001-7427-4651], Greene, Mark H [0000-0003-1852-9239], Institut Català de la Salut, [Figlioli G, Catucci I] IFOM - the FIRC Institute for Molecular Oncology, Genome Diagnostics Program, Milan, Italy. [Bogliolo M, Pujol R] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. Institute of Biomedical Research, Sant Pau Hospital, Barcelona, Spain. [Caleca L] Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy. [Lasheras SV] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Genètica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Hospital Universitari Vall d'Hebron, University of Iceland [Reykjavik], Università degli Studi di Milano = University of Milan (UNIMI), Universiteit Leiden-Universiteit Leiden, University of Pennsylvania-University of Pennsylvania, University of Pennsylvania, Georgetown University [Washington] (GU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universität Heidelberg [Heidelberg] = Heidelberg University, European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Human Genetics, Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Universitat Autònoma de Barcelona [Barcelona] (UAB), Università degli studi di Milano [Milano], University Hospitals of Leicester, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, University of Pisa, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pomeranian Medical University-International Hereditary Cancer Centre, McGill University, University of Kansas Medical Center [Lawrence], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology-University of Cambridge [UK] (CAM), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Università degli Studi di Roma 'La Sapienza' [Rome], IT University of Copenhagen, Laval University [Québec], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pontificia Universidad Javeriana, University of Santiago de Compostela, Læknadeild (HÍ), Faculty of Medicine (UI), Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), MINES ParisTech - École nationale supérieure des mines de Paris, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Universidade do Porto, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea, Against Breast Cancer, Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea. H2020, Cancer UK Grant, Canadian Institutes of Health Research, Ministère de Économie, de la science et de innovation (Canadá), NIH - National Cancer Institute (NCI) (Estados Unidos), Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Xunta de Galicia (España), Canadian Cancer Society, California Breast Cancer Research Program, California Department of Public Health, Medical Research Council (Reino Unido), Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases), Federal Ministry of Education & Research (Alemania), German Cancer Aid, Helsinki University Central Hospital Research Fund, Finlands Akademi (Finlandia), Deutsche Forschungsgemeinschaft (Alemania), Russian Foundation for Basic Research, Ministry of Science and Higher Education (Rusia), National Health and Medical Research Council (Australia), Biobanking and BioMolecular resources Research Infrastructure (Países Bajos), Estée Lauder Companies’ Breast Cancer Campaign, Swedish Research Council, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Lon V. Smith Foundation, Research Coincil of Lithuania, Italian Association for Cancer Research, University of Kansas. Cancer Center (Estados Unidos), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), French National Cancer Institute, Netherlands Organisation for Health Research and Development, Pink Ribbons Project, United States of Department of Health & Human Services, HUS Gynecology and Obstetrics, Clinicum, University of Helsinki, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, University Management, HUS Comprehensive Cancer Center, Biosciences, Helsinki University Hospital, and Lietuvos Mokslo Taryba (Lituania)
- Subjects
0301 basic medicine ,Gene mutation ,Càncer - Aspectes genètics ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Mama - Càncer ,Fanconi anemia ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Brjóstakrabbamein ,Medicine and Health Sciences ,Pharmacology (medical) ,FANCM ,631/208/68 ,skin and connective tissue diseases ,Cancer genetics ,Triple-negative breast cancer ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Manchester Cancer Research Centre ,Otros calificadores::Otros calificadores::/genética [Otros calificadores] ,article ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES] ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Life Sciences & Biomedicine ,3122 Cancers ,ABCTB Investigators ,lcsh:RC254-282 ,KConFab ,Olaparib ,Càncer de mama ,GEMO Study Collaborators ,03 medical and health sciences ,breast cancer ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,SDG 3 - Good Health and Well-being ,631/67/68 ,medicine ,Other subheadings::Other subheadings::/genetics [Other subheadings] ,Erfðafræði ,Radiology, Nuclear Medicine and imaging ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,ddc:610 ,Risk factor ,CHEK2 ,Krabbamein ,Cancer och onkologi ,FancM ,Science & Technology ,cancer ,MUTATIONS ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Biology and Life Sciences ,nutritional and metabolic diseases ,cancer genetics ,medicine.disease ,GENE ,Expressió gènica ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES] ,030104 developmental biology ,chemistry ,692/4028/67/68 ,Cancer and Oncology ,FANCONI-ANEMIA ,Cancer research ,gene expression ,C.5791C-GREATER-THAN-T ,business - Abstract
Publisher's version (útgefin grein), Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors., Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the “Fondo Europeo de Desarrollo Regional, una manera de hacer Europa” (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB “Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina” Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika” Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d’Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d’Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O’Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O’Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union’s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l’Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work 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 centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l’Alimentation, de l’Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the ‘Stichting tegen Kanker’. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov” and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, 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 NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education “Regional Initiative of Excellence” in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: 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 centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’) to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are 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 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. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization 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. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d’Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: 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. IOVHBOCS: Ministero della Salute and “5 × 1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.
- Published
- 2019
11. A detailed survey of agroecological status of Allium ursinum across the republic of Serbia: Mineral composition and bioaccumulation potential
- Author
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Stefan V. Gordanić, Aleksandar Ž. Kostić, Đurđa Krstić, Sandra Vuković, Sofija Kilibarda, Tatjana Marković, and Đorđe Moravčević
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PTEs ,biogenic elements ,Wild garlic ,Bioaccumulation factor ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
The purpose of this study was to determine the content of twenty-two biogenic elements (BEs) and potentially toxic elements (PTEs) in the soil and fresh Allium ursinum leaves from 43 different locations, in order to examine their bioaccumulation potential. Analyses of soil and plant material were carried out by using Inductively Coupled Plasma coupled with Optical Emission Spectroscopy (ICP-OES), a mercury analyzer (Hg), liquid chromatography (Cr), and AAS hybrid technique (As). The obtained results of the investigated elements were compared with the proposed limit values. The soil contamination factor (CF) as well as plant bioaccumulation factor (BAF) were calculated and the correlation analysis was performed. The results showed that the content of some BEs/PTEs in the soil were above the limit values, with two locations highly contaminated (CF > 6) with five (Cr(VI), Cu, Mn, Ni, V) and four (As, Co, Pb, V) elements. The content of As, Cd, Cr, and Pb in the leaves was higher than the permitted levels at some locations. The BAF was high (K, Ca, Zn, As), medium (Mg, Cu, B, Ni, Na, Pb), and low (Fe, Mn, Cr). The correlation between BEs/PTEs content in the leaves and soil was not significant, except for the following elements: Cd (0.37), Ca (0.34), As (0.36), Pb (0.30), and Na (0.25). The observed medium correlation suggested that the detected elements originated both from the atmosphere and the soil. Although A. ursinum at examined locations seemed to be mostly safe for consumption, a selective mechanism of adoption of certain BEs/PTEs requires continuous monitoring of their content in the future, to avoid quantities that can jeopardize human health through its consumption.
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- 2023
- Full Text
- View/download PDF
12. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation (vol 5, 4999, 2014)
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Ghoussaini, M., Edwards, S.L., Michailidou, K., Nord, S., Lari, R.C.S., Desai, K., Kar, S., Hillman, K.M., Kaufmann, S., Glubb, D.M., Beesley, J., Dennis, J., Bolla, M.K., Wang, Q., Dicks, E., Guo, Q., Schmidt, M.K., Shah, M., Luben, R., Brown, J., Czene, K., Darabi, H., Eriksson, M., Klevebring, D., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Lambrechts, D., Thienpont, B., Neven, P., Wildiers, H., Broeks, A., Van't Veer, L.J., Rutgers, E.J.T., Couch, F.J., Olson, J.E., Hallberg, E., Vachon, C., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Peto, J., dos-Santos-Silva, I., Gibson, L., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Hall, P., Li, J.M., Liu, J.J., Humphreys, K., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Matsuo, K., Ito, H., Iwata, H., Yatabe, Y., Guenel, P., Truong, T., Menegaux, F., Sanchez, M., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Benitez, J., Zamora, M., Perez, J.I.A., Menendez, P., Shu, X.O., Lu, W., Gao, Y.T., Cai, Q.Y., Cox, A., Cross, S.S., Reed, M.W.R., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Lindblom, A., Margolin, S., Teo, S.H., Yip, C.H., Lee, D.S.C., Wong, T.Y., Hooning, M.J., Martens, J.W.M., Collee, J.M., Deurzen, C.H.M. van, Hopper, J.L., Southey, M.C., Tsimiklis, H., Kapuscinski, M.K., Shen, C.Y., Wu, P.E., Yu, J.C., Chen, S.T., Alnaes, G.G., Borresen-Dale, A.L., Giles, G.G., Milne, R.L., McLean, C., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Hartman, M., Miao, H., Buhari, S.A.B.S., Teo, Y.Y., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M.J., Garcia-Closas, M., Figueroa, J., Chanock, S.J., Lissowska, J., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Brauch, H., Bruning, T., Koto, Y.D., Radice, P., Peterlongo, P., Bonanni, B., Volorio, S., Dork, T., Bogdanova, N.V., Helbig, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Slager, S., Toland, A.E., Ambrosone, C.B., Yannoukakos, D., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Hamann, U., Torres, D., Zheng, W., Long, J.R., Anton-Culver, H., Neuhausen, S.L., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Santiago, I. de, Carroll, J., Caldas, C., Brown, M.A., Lupien, M., Kristensen, V.N., Pharoah, P.D.P., Chenevix-Trench, G., French, J.D., Easton, D.F., Dunning, A.M., and Australian Ovarian Canc Management
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- 2018
13. Meeting abstracts from the Annual Conference on Hereditary Cancers 2016
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Cybulski, C., Kluźniak, W., Huzarski, T., Wokołorczyk, D., Kashyap, A., Jakubowska, A., Szwiec, M., Byrski, T., Dębniak, T., Górski, B., Sopik, V., Akbari, M. R., Sun, P., Gronwald, J., Narod, S. A., Lubiński, J., Dymerska, D., Kurzawski, G., Tutlewska, K., Kuswik, M., Rudnicka, H., Scott, R. J., Billings, R., Pławski, A., Lubinski, J., Gromowski, T., Kąklewski, K., Marciniak, W., Durda, K., Lener, M., Sukiennicki, G., Kaczmarek, K., Jaworska-Bieniek, K., Paszkowska-Szczur, K., Waloszczyk, P., Hemminki, K., Försti, A., Oszurek, O., Gugała, K., Stawicka, M., Morawiec, Z., Mierzwa, T., Falco, M., Janiszewska, H., Kilar, E., Marczyk, E., Kozak-Klonowska, B., Siołek, M., Surdyka, D., Wiśniowski, R., Posmyk, M., Domagała, P., Imyanitov, E. N., Muszyńska, M., Prajzendanc, K., Peruga, N., Morawski, A., Lener, M. R., Baszuk, P., Wiechowska-Kozłowska, A., Kładny, J., Pietrzak, S., Soluch, A., Plawski, A., Rashid, U. R., Naeemi, H., Muhammad, N., Loya, A., Yusuf, M. A., Savanevich, A., Aszurek, O., Mathe, A., Wong-Brown, M., Locke, W., Stirzaker, C., Braye, S. G., Forbes, J. F., Clark, S., Avery-Kiejda, K., Tomiczek-Szwiec, J., Jakubowicz, J., Sibilski, R., and Posmyk, R.
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Meeting Abstracts - Published
- 2017
14. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade
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Purrington, K.S., Slettedahl, S., Bolla, M.K., Michailidou, K., Czene, K., Nevanlinna, H., Bojesen, S.E., Andrulis, I.L., Cox, A., Hall, P., Carpenter, J., Yannoukakos, D., Haiman, C.A., Fasching, P.A., Mannermaa, A., Winqvist, R., Brenner, H., Lindblom, A., Chenevix-Trench, G., Benitez, J., Swerdlow, A., Kristensen, V., Guenel, P., Meindl, A., Darabi, H., Eriksson, M., Fagerholm, R., Aittomaki, K., Blomqvist, C., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Wang, X.S., Olswold, C., Olson, J.E., Mulligan, A.M., Knight, J.A., Tchatchou, S., Reed, M.W.R., Cross, S.S., Liu, J.J., Li, J.M., Humphreys, K., Clarke, C., Scott, R., Fostira, F., Fountzilas, G., Konstantopoulou, I., Henderson, B.E., Schumacher, F., Marchand, L. le, Ekici, A.B., Hartmann, A., Beckmann, M.W., Hartikainen, J.M., Kosma, V.M., Kataja, V., Jukkola-Vuorinen, A., Pylkas, K., Kauppila, S., Dieffenbach, A.K., Stegmaier, C., Arndt, V., Margolin, S., Balleine, R., Perez, J.I.A., Zamora, M.P., Menendez, P., Ashworth, A., Jones, M., Orr, N., Arveux, P., Kerbrat, P., Truong, T., Bugert, P., Toland, A.E., Ambrosone, C.B., Labreche, F., Goldberg, M.S., Dumont, M., Ziogas, A., Lee, E., Dite, G.S., Apicella, C., Southey, M.C., Long, J.R., Shrubsole, M., Deming-Halverson, S., Ficarazzi, F., Barile, M., Peterlongo, P., Durda, K., Jaworska-Bieniek, K., Tollenaar, R.A.E.M., Seynaeve, C., Bruning, T., Ko, Y.D., Deurzen, C.H.M. van, Martens, J.W.M., Kriege, M., Figueroa, J.D., Chanock, S.J., Lissowska, J., Tomlinson, I., Kerin, M.J., Miller, N., Schneeweiss, A., Tapper, W.J., Gerty, S.M., Durcan, L., Mclean, C., Milne, R.L., Baglietto, L., Silva, I.D., Fletcher, O., Johnson, N., Van'T Veer, L.J., Cornelissen, S., Forsti, A., Torres, D., Rudiger, T., Rudolph, A., Flesch-Janys, D., Nickels, S., Weltens, C., Floris, G., Moisse, M., Dennis, J., Wang, Q., Dunning, A.M., Shah, M., Brown, J., Simard, J., Anton-Culver, H., Neuhausen, S.L., Hopper, J.L., Bogdanova, N., Dork, T., Zheng, W., Radice, P., Jakubowska, A., Lubinski, J., Devillee, P., Brauch, H., Hooning, M., Garcia-Closas, M., Sawyer, E., Burwinkel, B., Marmee, F., Eccles, D.M., Giles, G.G., Peto, J., Schmidt, M., Broeks, A., Hamann, U., Chang-Claude, J., Lambrechts, D., Pharoah, P.D.P., Easton, D., Pankratz, V.S., Slager, S., Vachon, C.M., Couch, F.J., ABCTB Investigators, Australian Ovarian Canc Study Grp, kConFab Investigators, GENICA Network, Medical Oncology, Pathology, and Clinical Genetics
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Oncology ,Candidate gene ,Fibroblast Growth Factor ,amplification ,cancer susceptibility loci ,Bioinformatics ,medicine.disease_cause ,Medical and Health Sciences ,prostate-cancer ,Prostate cancer ,Risk Factors ,Medizinische Fakultät ,Genetics (clinical) ,Genetics & Heredity ,tacc2 ,Association Studies Articles ,Single Nucleotide ,General Medicine ,Biological Sciences ,ddc ,risk loci ,cell-division ,kConFab Investigators ,Female ,GENICA Network ,Type 2 ,Receptor ,Australian Ovarian Cancer Study Group ,Breast Neoplasms ,Carrier Proteins ,Case-Control Studies ,Haplotypes ,Humans ,Neoplasm Staging ,Polymorphism, Single Nucleotide ,Receptor, Fibroblast Growth Factor, Type 2 ,Tumor Suppressor Proteins ,Genetic Variation ,Molecular Biology ,Genetics ,medicine.medical_specialty ,Mitotic index ,ABCTB Investigators ,Single-nucleotide polymorphism ,Biology ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,ddc:610 ,Polymorphism ,Lung cancer ,Odds ratio ,medicine.disease ,genome-wide association ,lung-cancer ,progression ,Carcinogenesis - Abstract
Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.
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- 2014
15. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk
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Lin, W.Y., Camp, N.J., Ghoussaini, M., Beesley, J., Michailidou, K., Hopper, J.L., Apicella, C., Southey, M.C., Stone, J., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Rutgers, E.J.T., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Peto, J., Dos-Santos-Silva, I., Fletcher, O., Johnson, N., Bolla, M.K., Wang, Q., Dennis, J., Sawyer, E.J., Cheng, T., Tomlinson, I., Kerin, M.J., Miller, N., Marme, F., Surowy, H.M., Burwinkel, B., Guenel, P., Truong, T., Menegaux, F., Mulot, C., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrera, D., Anton-Culver, H., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Meindl, A., Lichtner, P., Schmutzler, R.K., Muller-Myhsok, B., Brauch, H., Bruning, T., Ko, Y.D., Tessier, D.C., Vincent, D., Bacot, F., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Khan, S., Matsuo, K., Ito, H., Iwata, H., Horio, A., Bogdanova, N.V., Antonenkova, N.N., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Neven, P., Wauters, E., Wildiers, H., Lambrechts, D., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Manoukian, S., Bonanni, B., Couch, F.J., Wang, X.S., Vachon, C., Purrington, K., Giles, G.G., Milne, R.L., Mclean, C., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Teo, S.H., Yip, C.H., Hassan, N., Vithana, E.N., Kristensen, V., Zheng, W., Deming-Halverson, S., Shrubsole, M.J., Long, J.R., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Garcia-Closas, M., Figueroa, J., Lissowska, J., Brinton, L., Czene, K., Darabi, H., Eriksson, M., Brand, J.S., Hooning, M.J., Hollestelle, A., Ouweland, A.M.W. van den, Jager, A., Li, J.M., Liu, J.J., Humphreys, K., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Cross, S.S., Reed, M.W.R., Blot, W., Signorello, L.B., Cai, Q.Y., Pharoah, P.D.P., Perkins, B., Shah, M., Blows, F.M., Kang, D., Yoo, K.Y., Noh, D.Y., Hartman, M., Miao, H., Chia, K.S., Putti, T.C., Hamann, U., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Slager, S., Toland, A.E., Yannoukakos, D., Shen, C.Y., Hsiung, C.N., Wu, P.E., Ding, S.L., Ashworth, A., Jones, M., Orr, N., Swerdlow, A.J., Tsimiklis, H., Makalic, E., Schmidt, D.F., Bui, Q.M., Chanock, S.J., Hunter, D.J., Hein, R., Dahmen, N., Beckmann, L., Aaltonen, K., Muranen, T.A., Heikkinen, T., Irwanto, A., Rahman, N., Turnbull, C.A., Waisfisz, Q., Meijers-Heijboer, H.E.J., Adank, M.A., Luijt, R.B. van der, Hall, P., Chenevix-Trench, G., Dunning, A., Easton, D.F., Cox, A., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, Breast Ovarian Canc Susceptibility, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Cardiothoracic Surgery, Cancer Center Amsterdam, Amsterdam Reproduction & Development (AR&D), Human Genetics, Human genetics, CCA - Oncogenesis, Ghoussaini, Maya [0000-0002-2415-2143], Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
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Genotyping Techniques ,Research Support, U.S. Gov't, P.H.S ,CASP8 and FADD-Like Apoptosis Regulating Protein ,Genome-wide association study ,P.H.S ,Medical and Health Sciences ,Breast and Ovarian Cancer Susceptibility (BOCS) Study ,Medizinische Fakultät ,Genetics(clinical) ,Non-U.S. Gov't ,Genetics (clinical) ,Genetics ,Genetics & Heredity ,variants ,Caspase 8 ,Research Support, Non-U.S. Gov't ,Association Studies Articles ,General Medicine ,Biological Sciences ,ddc ,Chromosomes, Human, Pair 2 ,kConFab Investigators ,Female ,GENICA Network ,Australian Ovarian Cancer Study Group ,European Continental Ancestry Group ,Non-P.H.S ,Single-nucleotide polymorphism ,Breast Neoplasms ,Biology ,Research Support ,Polymorphism, Single Nucleotide ,White People ,N.I.H ,Breast cancer ,Research Support, N.I.H., Extramural ,SDG 3 - Good Health and Well-being ,medicine ,Journal Article ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,gene ,Genotyping ,Molecular Biology ,Genetic association ,disease ,Extramural ,Proteins ,Odds ratio ,medicine.disease ,susceptibility loci ,Minor allele frequency ,Case-Control Studies ,genome-wide association ,enhancers ,U.S. Gov't ,casp8 ,Research Support, U.S. Gov't, Non-P.H.S ,Genome-Wide Association Study - Abstract
Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.
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- 2016
16. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
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Pfeiler, G, Vigorito, E, Kuchenbaecker, KB, Beesley, J, Adlard, J, Agnarsson, BA, Andrulis, IL, Arun, BK, Barjhoux, L, Belotti, M, Benitez, J, Berger, A, Phelan, CM, Piedmonte, M, Poppe, B, Pujana, MA, Radice, P, Rennert, G, Rodriguez, GC, Rookus, MA, Ross, EA, Bojesen, A, Schmutzler, RK, Simard, J, Singer, CF, Slavin, TP, Soucy, P, Southey, M, Steinemann, D, Stoppa-Lyonnet, D, Sukiennicki, G, Sutter, C, Bonanni, B, Szabo, CI, Tea, MK, Teixeira, MR, Teo, SH, Terry, MB, Thomassen, M, Tibiletti, MG, Tihomirova, L, Tognazzo, S, van Rensburg, EJ, Brewer, C, Varesco, L, Varon-Mateeva, R, Vratimos, A, Weitzel, JN, McGuffog, L, Kirk, J, Toland, AE, Hamann, U, Lindor, N, Ramus, SJ, Caldes, T, Greene, MH, Couch, FJ, Offit, K, Pharoah, PDP, Chenevix-Trench, G, Antoniou, AC, Prokunina-Olsson, L, Caligo, MA, Campbell, I, Chan, SB, Claes, KBM, Cohn, DE, Cook, J, Daly, MB, Damiola, F, Davidson, R, Pauw, AD, Delnatte, C, Diez, O, Domchek, SM, Dumont, M, Durda, K, Dworniczak, B, Easton, DF, Eccles, D, Edwinsdotter Ardnor, C, Eeles, R, Ejlertsen, B, Ellis, S, Evans, G, Feliubadalo, L, Fostira, F, Foulkes, WD, Friedman, E, Frost, D, Gaddam, P, Ganz, PA, Garber, J, Garcia-Barberan, V, Gauthier-Villars, M, Gehrig, A, Gerdes, AM, Giraud, S, Godwin, AK, Goldgar, DE, Hake, CR, Hansen, TVO, Healey, S, Hodgson, S, Hogervorst, FBL, Houdayer, C, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Izquierdo, A, Jacobs, L, Jakubowska, A, Janavicius, R, Jaworska-Bieniek, K, Jensen, UB, John, EM, Vijai, J, Karlan, BY, Kast, K, Investigators, K, Khan, S, Kwong, A, Laitman, Y, Lester, J, Lesueur, F, Liljegren, A, Lubinski, J, Mai, PL, Manoukian, S, Mazoyer, S, Meindl, A, Mensenkamp, AR, Montagna, M, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Niederacher, D, Olah, E, Olopade, OI, Ong, KR, Osorio, A, Park, SK, Paulsson-Karlsson, Y, Pedersen, IS, Peissel, B, and Peterlongo, P
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endocrine system diseases ,skin and connective tissue diseases - Abstract
Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA 1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population
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- 2016
17. PALB2, CHEK2 and ATM rare variants and cancer risk:data from COGS
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Southey, M. C. (Melissa C.), Goldgar, D. E. (David E.), Winqvist, R. (Robert), Pylkäs, K. (Katri), Couch, F. (Fergus), Tischkowitz, M. (Marc), Foulkes, W. D. (William D.), Dennis, J. (Joe), Michailidou, K. (Kyriaki), van Rensburg, E. J. (Elizabeth J.), Heikkinen, T. (Tuomas), Nevanlinna, H. (Heli), Hopper, J. L. (John L.), Doerk, T. (Thilo), Claes, K. B. (Kathleen B. M.), Reis-Filho, J. (Jorge), Teo, Z. L. (Zhi Ling), Radice, P. (Paolo), Catucci, I. (Irene), Peterlongo, P. (Paolo), Tsimiklis, H. (Helen), Odefrey, F. A. (Fabrice A.), Dowty, J. G. (James G.), Schmidt, M. K. (Marjanka K.), Broeks, A. (Annegien), Hogervorst, F. B. (Frans B.), Verhoef, S. (Senno), Carpenter, J. (Jane), Clarke, C. (Christine), Scott, R. J. (Rodney J.), Fasching, P. A. (Peter A.), Haeberle, L. (Lothar), Ekici, A. B. (Arif B.), Beckmann, M. W. (Matthias W.), Peto, J. (Julian), dos-Santos-Silva, I. (Isabel), Fletcher, O. (Olivia), Johnson, N. (Nichola), Bolla, M. K. (Manjeet K.), Sawyer, E. J. (Elinor J.), Tomlinson, I. (Ian), Kerin, M. J. (Michael J.), Miller, N. (Nicola), Marme, F. (Federik), Burwinkel, B. (Barbara), Yang, R. (Rongxi), Guenel, P. (Pascal), Menegaux, F. (Florence), Sanchez, M. (Marie), Bojesen, S. (Stig), Nielsen, S. F. (Sune F.), Flyger, H. (Henrik), Benitez, J. (Javier), Pilar Zamora, M. (M.), Arias Perez, J. I. (Jose Ignacio), Menendez, P. (Primitiva), Anton-Culver, H. (Hoda), Neuhausen, S. (Susan), Ziogas, A. (Argyrios), Clarke, C. A. (Christina A.), Brenner, H. (Hermann), Arndt, V. (Volker), Stegmaier, C. (Christa), Brauch, H. (Hiltrud), Bruening, T. (Thomas), Ko, Y.-D. (Yon-Dschun), Muranen, T. A. (Taru A.), Aittomaki, K. (Kristiina), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia V.), Antonenkova, N. N. (Natalia N.), Lindblom, A. (Annika), Margolin, S. (Sara), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V.-M. (Veli-Matti), Hartikainen, J. M. (Jaana M.), Spurdle, A. B. (Amanda B.), Wauters, E. (Els), Smeets, D. (Dominiek), Beuselinck, B. (Benoit), Floris, G. (Giuseppe), Chang-Claude, J. (Jenny), Rudolph, A. (Anja), Seibold, P. (Petra), Flesch-Janys, D. (Dieter), Olson, J. E. (Janet E.), Vachon, C. (Celine), Pankratz, V. S. (Vernon S.), McLean, C. (Catriona), Haiman, C. A. (Christopher A.), Henderson, B. E. (Brian E.), Schumacher, F. (Fredrick), Le Marchand, L. (Loic), Kristensen, V. (Vessela), Alnaes, G. G. (Grethe Grenaker), Zheng, W. (Wei), Hunter, D. J. (David J.), Lindstrom, S. (Sara), Hankinson, S. E. (Susan E.), Kraft, P. (Peter), Andrulis, I. (Irene), Knight, J. A. (Julia A.), Glendon, G. (Gord), Mulligan, A. M. (Anna Marie), Jukkola-Vuorinen, A. (Arja), Grip, M. (Mervi), Kauppila, S. (Saila), Devilee, P. (Peter), Tollenaar, R. A. (Robert A. E. M.), Seynaeve, C. (Caroline), Hollestelle, A. (Antoinette), Garcia-Closas, M. (Montserrat), Figueroa, J. (Jonine), Chanock, S. J. (Stephen J.), Lissowska, J. (Jolanta), Czene, K. (Kamila), Darabi, H. (Hatef), Eriksson, M. (Mikael), Eccles, D. M. (Diana M.), Rafiq, S. (Sajjad), Tapper, W. J. (William J.), Gerty, S. M. (Sue M.), Hooning, M. J. (Maartje J.), Martens, J. W. (John W. M.), Collee, J. M. (J. Margriet), Tilanus-Linthorst, M. (Madeleine), Hall, P. (Per), Li, J. (Jingmei), Brand, J. S. (Judith S.), Humphreys, K. (Keith), Cox, A. (Angela), Reed, M. W. (Malcolm W. R.), Luccarini, C. (Craig), Baynes, C. (Caroline), Dunning, A. M. (Alison M.), Hamann, U. (Ute), Torres, D. (Diana), Ulmer, H. U. (Hans Ulrich), Ruediger, T. (Thomas), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Slager, S. (Susan), Toland, A. E. (Amanda E.), Ambrosone, C. B. (Christine B.), Yannoukakos, D. (Drakoulis), Swerdlow, A. (Anthony), Ashworth, A. (Alan), Orr, N. (Nick), Jones, M. (Michael), Gonzalez-Neira, A. (Anna), Pita, G. (Guillermo), Rosario Alonso, M. (M.), Alvarez, N. (Nuria), Herrero, D. (Daniel), Tessier, D. C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Simard, J. (Jacques), Dumont, M. (Martine), Soucy, P. (Penny), Eeles, R. (Rosalind), Muir, K. (Kenneth), Wiklund, F. (Fredrik), Gronberg, H. (Henrik), Schleutker, J. (Johanna), Nordestgaard, B. G. (Borge G.), Weischer, M. (Maren), Travis, R. C. (Ruth C.), Neal, D. (David), Donovan, J. L. (Jenny L.), Hamdy, F. C. (Freddie C.), Khaw, K.-T. (Kay-Tee), Stanford, J. L. (Janet L.), Blot, W. J. (William J.), Thibodeau, S. (Stephen), Schaid, D. J. (Daniel J.), Kelley, J. L. (Joseph L.), Maier, C. (Christiane), Kibel, A. S. (Adam S.), Cybulski, C. (Cezary), Cannon-Albright, L. (Lisa), Butterbach, K. (Katja), Park, J. (Jong), Kaneva, R. (Radka), Batra, J. (Jyotsna), Teixeira, M. R. (Manuel R.), Kote-Jarai, Z. (Zsofia), Al Olama, A. A. (Ali Amin), Benlloch, S. (Sara), Renner, S. P. (Stefan P.), Hartmann, A. (Arndt), Hein, A. (Alexander), Ruebner, M. (Matthias), Lambrechts, D. (Diether), Van Nieuwenhuysen, E. (Els), Vergote, I. (Ignace), Lambretchs, S. (Sandrina), Doherty, J. A. (Jennifer A.), Rossing, M. A. (Mary Anne), Nickels, S. (Stefan), Eilber, U. (Ursula), Wang-Gohrke, S. (Shan), Odunsi, K. (Kunle), Sucheston-Campbell, L. E. (Lara E.), Friel, G. (Grace), Lurie, G. (Galina), Killeen, J. L. (Jeffrey L.), Wilkens, L. R. (Lynne R.), Goodman, M. T. (Marc T.), Runnebaum, I. (Ingo), Hillemanns, P. A. (Peter A.), Pelttari, L. M. (Liisa M.), Butzow, R. (Ralf), Modugno, F. (Francesmary), Edwards, R. P. (Robert P.), Ness, R. B. (Roberta B.), Moysich, K. B. (Kirsten B.), du Bois, A. (Andreas), Heitz, F. (Florian), Harter, P. (Philipp), Kommoss, S. (Stefan), Karlan, B. Y. (Beth Y.), Walsh, C. (Christine), Lester, J. (Jenny), Jensen, A. (Allan), Kjaer, S. K. (Susanne Kruger), Hogdall, E. (Estrid), Peissel, B. (Bernard), Bonanni, B. (Bernardo), Bernard, L. (Loris), Goode, E. L. (Ellen L.), Fridley, B. L. (Brooke L.), Vierkant, R. A. (Robert A.), Cunningham, J. M. (Julie M.), Larson, M. C. (Melissa C.), Fogarty, Z. C. (Zachary C.), Kalli, K. R. (Kimberly R.), Liang, D. (Dong), Lu, K. H. (Karen H.), Hildebrandt, M. A. (Michelle A. T.), Wu, X. (Xifeng), Levine, D. A. (Douglas A.), Dao, F. (Fanny), Bisogna, M. (Maria), Berchuck, A. (Andrew), Iversen, E. S. (Edwin S.), Marks, J. R. (Jeffrey R.), Akushevich, L. (Lucy), Cramer, D. W. (Daniel W.), Schildkraut, J. (Joellen), Terry, K. L. (Kathryn L.), Poole, E. M. (Elizabeth M.), Stampfer, M. (Meir), Tworoger, S. S. (Shelley S.), Bandera, E. V. (Elisa V.), Orlow, I. (Irene), Olson, S. H. (Sara H.), Bjorge, L. (Line), Salvesen, H. B. (Helga B.), van Altena, A. M. (Anne M.), Aben, K. K. (Katja K. H.), Kiemeney, L. A. (Lambertus A.), Massuger, L. F. (Leon F. A. G.), Pejovic, T. (Tanja), Bean, Y. (Yukie), Brooks-Wilson, A. (Angela), Kelemen, L. E. (Linda E.), Cook, L. S. (Linda S.), Le, N. D. (Nhu D.), Grski, B. (Bohdan), Gronwald, J. (Jacek), Menkiszak, J. (Janusz), Hogdall, C. K. (Claus K.), Lundvall, L. (Lene), Nedergaard, L. (Lotte), Engelholm, S. A. (Svend Aage), Dicks, E. (Ed), Tyrer, J. (Jonathan), Campbell, I. (Ian), McNeish, I. (Iain), Paul, J. (James), Siddiqui, N. (Nadeem), Glasspool, R. (Rosalind), Whittemore, A. S. (Alice S.), Rothstein, J. H. (Joseph H.), McGuire, V. (Valerie), Sieh, W. (Weiva), Cai, H. (Hui), Shu, X.-O. (Xiao-Ou), Teten, R. T. (Rachel T.), Sutphen, R. (Rebecca), McLaughlin, J. R. (John R.), Narod, S. A. (Steven A.), Phelan, C. M. (Catherine M.), Monteiro, A. N. (Alvaro N.), Fenstermacher, D. (David), Lin, H.-Y. (Hui-Yi), Permuth, J. B. (Jennifer B.), Sellers, T. A. (Thomas A.), Chen, Y. A. (Y. Ann), Tsai, Y.-Y. (Ya-Yu), Chen, Z. (Zhihua), Gentry-Maharaj, A. (Aleksandra), Gayther, S. A. (Simon A.), Ramus, S. J. (Susan J.), Menon, U. (Usha), Wu, A. H. (Anna H.), Pearce, C. L. (Celeste L.), Van den Berg, D. (David), Pike, M. C. (Malcolm C.), Dansonka-Mieszkowska, A. (Agnieszka), Plisiecka-Halasa, J. (Joanna), Moes-Sosnowska, J. (Joanna), Kupryjanczyk, J. (Jolanta), Pharoah, P. D. (Paul D. P.), Song, H. (Honglin), Winship, I. (Ingrid), Chenevix-Trench, G. (Georgia), Giles, G. G. (Graham G.), Tavtigian, S. V. (Sean V.), Easton, D. F. (Doug F.), and Milne, R. L. (Roger L.)
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skin and connective tissue diseases - Abstract
Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p = 7.1 × 10⁻⁵), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p = 6.9 × 10⁻⁸) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p = 0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p ≤ 0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p = 0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p = 0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
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- 2016
18. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
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Vigorito, E., Kuchenbaecker, K.B., Beesley, J., Adlard, J., Agnarsson, B.A., Andrulis, I.L., Arun, B.K., Barjhoux, L., Belotti, M., Benitez, J., Berger, A., Bojesen, A., Bonanni, B., Brewer, C., Caldes, T., Caligo, M.A., Campbell, I., Chan, S.B., Claes, K.B., Cohn, D.E., Cook, J., Daly, M.B., Damiola, F., Davidson, R., Pauw, A. de, Delnatte, C., Diez, O., Domchek, S.M., Dumont, M., Durda, K., Dworniczak, B., Easton, D.F., Eccles, D., Edwinsdotter Ardnor, C., Eeles, R., Ejlertsen, B., Ellis, S., Evans, D.G., Feliubadalo, L., Fostira, F., Foulkes, W.D., Friedman, E., Frost, D., Gaddam, P., Ganz, P.A., Garber, J., Garcia-Barberan, V., Gauthier-Villars, M., Gehrig, A., Gerdes, A.M., Giraud, S., Godwin, A.K., Goldgar, D.E., Hake, C.R., Hansen, T.V., Healey, S., Hodgson, S., Hogervorst, F.B., Houdayer, C., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Izquierdo, A., Jacobs, L, Jakubowska, A., Janavicius, R., Jaworska-Bieniek, K., Jensen, U.B., John, E.M., Vijai, J., Karlan, B.Y., Kast, K., Khan, S., Kwong, A., Laitman, Y., Lester, J., Lesueur, F., Liljegren, A., Lubinski, J., Mai, P.L., Manoukian, S., Mazoyer, S., Meindl, A., Mensenkamp, A.R., Montagna, M., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Niederacher, D., Olah, E., Olopade, O.I., Ong, K.R., Osorio, A., Park, S.K., Paulsson-Karlsson, Y., Pedersen, I.S., Peissel, B., Peterlongo, P., and Prokunina-Olsson, Ludmila
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endocrine system diseases ,General Science & Technology ,Chromosomes ,Rare Diseases ,Clinical Research ,Breast Cancer ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Genetic Predisposition to Disease ,Aetiology ,Polymorphism ,skin and connective tissue diseases ,Cancer ,Ovarian Neoplasms ,Prevention ,Genetic Carrier Screening ,Human Genome ,Chromosome Mapping ,Single Nucleotide ,BRCA1 ,BRCA2 ,Ovarian Cancer ,Genes ,Female ,KConFab Investigators ,Human ,Pair 9 - Abstract
Contains fulltext : 172560.PDF (Publisher’s version ) (Open Access) Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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- 2016
19. A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers
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Ding, Y.C., McGuffog, L., Healey, S., Friedman, E., Laitman, Y., Shani-Paluch-Shimon, Kaufman, B., Liljegren, A., Lindblom, A., Olsson, H., Kristoffersson, U., Stenmark-Askmalm, M., Melin, B., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Gronwald, J., Huzarski, T., Cybulski, C., Byrski, T., Osorio, A., Cajal, T.R., Stavropoulou, A.V., Benitez, J., Hamann, U., Rookus, M., Aalfs, C.M., Lange, J.L. de, Meijers-Heijboer, H.E.J., Oosterwijk, J.C., Asperen, C.J. van, Garcia, E.B.G., Hoogerbrugge, N., Jager, A., Luijt, R.B. van der, Easton, D.F., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Izatt, L., Eeles, R., Adlard, J., Davidson, R., Eccles, D., Cole, T., Cook, J., Brewer, C., Tischkowitz, M., Godwin, A.K., Pathak, H., Stoppa-Lyonnet, D., Sinilnikova, O.M., Mazoyer, S., Barjhoux, L., Leone, M., Gauthier-Villars, M., Caux-Moncoutier, V., Pauw, A. de, Hardouin, A., Berthet, P., Dreyfus, H., Ferrer, S.F., Collonge-Rame, M.A., Sokolowska, J., Buys, S., Daly, M., Miron, A., Terry, M.B., Chung, W., John, E.M., Southey, M., Goldgar, D., Singer, C.F., Tea, M.K.M., Gschwantler-Kaulich, D., Fink-Retter, A., Hansen, T.V.O., Ejlertsen, B., Johannsson, O.T., Offit, K., Sarrel, K., Gaudet, M.M., Vijai, J., Robson, M., Piedmonte, M.R., Andrews, L., Cohn, D., DeMars, L.R., DiSilvestro, P., Rodriguez, G., Toland, A.E., Montagna, M., Agata, S., Imyanitov, E., Isaacs, C., Janavicius, R., Lazaro, C., Blanco, I., Ramus, S.J., Sucheston, L., Karlan, B.Y., Gross, J., Ganz, P.A., Beattie, M.S., Schmutzler, R.K., Wappenschmidt, B., Meindl, A., Arnold, N., Niederacher, D., Preisler-Adams, S., Gadzicki, D., Varon-Mateeva, R., Deissler, H., Gehrig, A., Sutter, C., Kast, K., Nevanlinna, H., Aittomaki, K., Simard, J., Spurdle, A.B., Beesley, J., Chen, X.Q., Tomlinson, G.E., Weitzel, J., Garber, J.E., Olopade, O.I., Rubinstein, W.S., Tung, N., Blum, J.L., Narod, S.A., Brummel, S., Gillen, D.L., Lindor, N., Fredericksen, Z., Pankratz, V.S., Couch, F.J., Radice, P., Peterlongo, P., Greene, M.H., Loud, J.T., Mai, P.L., Andrulis, I.L., Glendon, G., Ozcelik, H., Gerdes, A.M., Thomassen, M., Jensen, U.B., Skytte, A.B., Caligo, M.A., Lee, A., Chenevix-Trench, G., Antoniou, A.C., Neuhausen, S.L., SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators, KConFab Investigators, OCGN, Consortium Investigators Modifiers, Human genetics, CCA - Oncogenesis, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human Genetics, Cancer Center Amsterdam, Amsterdam Reproduction & Development (AR&D), Medical Oncology, Clinical Genetics, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Targeted Gynaecologic Oncology (TARGON)
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Nonsynonymous substitution ,endocrine system diseases ,Epidemiology ,Genes, BRCA2 ,Genes, BRCA1 ,Cohort Studies ,0302 clinical medicine ,Genotype ,skin and connective tissue diseases ,Ovarian Neoplasms ,0303 health sciences ,GENETIC-VARIATION ,INSULIN ,3. Good health ,FAMILY ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Female ,Cohort study ,EXPRESSION ,AMINO-ACID POLYMORPHISM ,endocrine system ,PROTEINS ,Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1] ,NEOPLASIA ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Breast cancer ,SDG 3 - Good Health and Well-being ,Translational research [ONCOL 3] ,GROWTH-FACTOR-I ,medicine ,Humans ,Genetic Predisposition to Disease ,IGF ,030304 developmental biology ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,RECEPTOR ,Retrospective cohort study ,medicine.disease ,IRS1 ,Mutation ,Cancer research ,Insulin Receptor Substrate Proteins ,Ovarian cancer - Abstract
Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods:IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06–1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39–3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28–2.70; class I HR, 0.86; 95%CI, 0.69–1.09; Pdifference, 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03). Conclusion: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(8); 1362–70. ©2012 AACR.
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- 2012
20. Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
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Mavaddat, N., Pharoah, P.D.P., Michailidou, K., Tyrer, J., Brook, M.N., Bolla, M.K., Wang, Q., Dennis, J., Dunning, A.M., Shah, M., Luben, R., Brown, J., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Czene, K., Darabi, H., Eriksson, M., Peto, J., dos-Santos-Silva, I., Dudbridge, F., Johnson, N., Schmidt, M.K., Broeks, A., Verhoef, S., Rutgers, E.J., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M.J., Figueroa, J., Chanock, S.J., Brinton, L., Lissowska, J., Couch, F.J., Olson, J.E., Vachon, C., Pankratz, V.S., Lambrechts, D., Wildiers, H., Ongeval, C. van, Limbergen, E. van, Kristensen, V., Alnaes, G.G., Nord, S., Borresen-Dale, A.L., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Trentham-Dietz, A., Newcomb, P., Titus, L., Egan, K.M., Hunter, D.J., Lindstrom, S., Tamimi, R.M., Kraft, P., Rahman, N., Turnbull, C., Renwick, A., Seal, S., Li, J.M., Liu, J.J., Humphreys, K., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Bogdanova, N.V., Antonenkova, N.N., Dork, T., Anton-Culver, H., Neuhausen, S.L., Ziogas, A., Bernstein, L., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Cox, A., Cross, S.S., Reed, M.W.R., Khusnutdinova, E., Bermisheva, M., Prokofyeva, D., Takhirova, Z., Meindl, A., Schmutzler, R.K., Sutter, C., Yang, R.X., Schurmann, P., Bremer, M., Christiansen, H., Park-Simon, T.W., Hillemanns, P., Guenel, P., Truong, T., Menegaux, F., Sanchez, M., Radice, P., Peterlongo, P., Manoukian, S., Pensotti, V., Hopper, J.L., Tsimiklis, H., Apicella, C., Southey, M.C., Brauch, H., Bruning, T., Ko, Y.D., Sigurdson, A.J., Doody, M.M., Hamann, U., Torres, D., Ulmer, H.U., Forsti, A., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Chenevix-Trench, G., Balleine, R., Giles, G.G., Milne, R.L., McLean, C., Lindblom, A., Margolin, S., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Eilber, U., Wang-Gohrke, S., Hooning, M.J., Hollestelle, A., Ouweland, A.M.W. van den, Koppert, L.B., Carpenter, J., Clarke, C., Scott, R., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Brenner, H., Arndt, V., Stegmaier, C., Dieffenbach, A.K., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Offit, K., Vijai, J., Robson, M., Rau-Murthy, R., Dwek, M., Swann, R., Perkins, K.A., Goldberg, M.S., Labreche, F., Dumont, M., Eccles, D.M., Tapper, W.J., Rafiq, S., John, E.M., Whittemore, A.S., Slager, S., Yannoukakos, D., Toland, A.E., Yao, S., Zheng, W., Halverson, S.L., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Simard, J., Hall, P., Easton, D.F., Garcia-Closas, M., Clinical Genetics, Medical Oncology, Surgery, Department of Obstetrics and Gynecology, Clinicum, Medicum, Kristiina Aittomäki / Principal Investigator, Department of Medical and Clinical Genetics, Department of Oncology, HUS Gynecology and Obstetrics, Mavaddat, Nasim [0000-0003-0307-055X], Pharoah, Paul [0000-0001-8494-732X], Tyrer, Jonathan [0000-0003-3724-4757], Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Luben, Robert [0000-0002-5088-6343], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
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Adult ,Genotype ,3122 Cancers ,Breast Neoplasms ,consortium ,Polymorphism, Single Nucleotide ,Risk Assessment ,Article ,prevention ,SDG 3 - Good Health and Well-being ,Predictive Value of Tests ,Risk Factors ,3123 Gynaecology and paediatrics ,Biomarkers, Tumor ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,family-history ,Aged ,prostate ,Gene Expression Profiling ,subtypes ,Middle Aged ,susceptibility loci ,Europe ,Gene Expression Regulation, Neoplastic ,Receptors, Estrogen ,Tumor Markers, Biological ,Cancer and Oncology ,genome-wide association ,Female ,women - Abstract
Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1 of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. © 2015 © The Author 2015. Published by Oxford University Press.
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- 2015
21. Identification of novel genetic markers of breast cancer survival
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Guo, Q., Schmidt, M.K., Kraft, P., Canisius, S., Chen, C., Khan, S., Tyrer, J., Bolla, M.K., Wang, Q., Dennis, J., Michailidou, K., Lush, M., Kar, S., Beesley, J., Dunning, A.M., Shah, M., Czene, K., Darabi, H., Eriksson, M., Lambrechts, D., Weltens, C., Leunen, K., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Blomqvist, C., Aittomaki, K., Fagerholm, R., Muranen, T.A., Couch, F.J., Olson, J.E., Vachon, C., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Broeks, A., Hogervorst, F.B., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Hopper, J.L., Tsimiklis, H., Apicella, C., Southey, M.C., Cox, A., Cross, S.S., Reed, M.W.R., Giles, G.G., Milne, R.L., McLean, C., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Hooning, M.J., Hollestelle, A., Martens, J.W.M., Ouweland, A.M.W. van den, Marme, F., Schneeweiss, A., Yang, R.X., Burwinkel, B., Figueroa, J., Chanock, S.J., Lissowska, J., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Brenner, H., Dieffenbach, A.K., Arndt, V., Holleczek, B., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Li, J.M., Brand, J.S., Humphreys, K., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Radice, P., Peterlongo, P., Bonanni, B., Mariani, P., Fasching, P.A., Beckmann, M.W., Hein, A., Ekici, A.B., Chenevix-Trench, G., Balleine, R., Phillips, K.A., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Hamann, U., Kabisch, M., Ulmer, H.U., Rudiger, T., Margolin, S., Kristensen, V., Nord, S., Evans, D.G., Abraham, J.E., Earl, H.M., Hiller, L., Dunn, J.A., Bowden, S., Berg, C., Campa, D., Diver, W.R., Gapstur, S.M., Gaudet, M.M., Hankinson, S.E., Hoover, R.N., Husing, A., Kaaks, R., Machiela, M.J., Willett, W., Barrdahl, M., Canzian, F., Chin, S.F., Caldas, C., Hunter, D.J., Lindstrom, S., Garcia-Closas, M., Hall, P., Easton, D.F., Eccles, D.M., Rahman, N., Nevanlinna, H., Pharoah, P.D.P., kConFab Investigators, Tyrer, Jonathan [0000-0003-3724-4757], Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Abraham, Jean [0000-0003-0688-4807], Earl, Helena [0000-0003-1549-8094], Chin, Suet-Feung [0000-0001-5697-1082], Caldas, Carlos [0000-0003-3547-1489], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], and Apollo - University of Cambridge Repository
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Genetic Markers ,Genotype ,Receptors, Estrogen ,Humans ,Breast Neoplasms ,Female ,Genetic Predisposition to Disease ,Prognosis ,Polymorphism, Single Nucleotide ,Survival Analysis ,White People - Abstract
BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. CONCLUSIONS: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.
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- 2015
22. Common germline polymorphisms\ud associated with breast cancer-specific survival
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Pirie, A., Guo, Q., Kraft, P., Canisius, S., Eccles, D.M., Rahman, N., Nevanlinna, H., Chen, C., Khan, S., Tyrer, J., Bolla, M.K., Wang, Q., Dennis, J., Michailidou, K., Lush, M., Dunning, A.M., Shah, M., Czene, K., Darabi, H., Eriksson, M., Lambrechts, D., Weltens, C., Leunen, K., van Ongeval, C., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Rudolph, A., Seibold, P., Flesch-Janys, D., Blomqvist, C., Aittomaki, K., Fagerholm, R., Muranen, T.A., Olsen, J.E., Hallberg, E., Vachon, C., Knight, J.A., Glendon, G., Mulligan, A.M., Broeks, A., Cornelissen, S., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Hopper, J.L., Tsimiklis, H., Apicella, C., Southey, M.C., Cross, S.S., Reed, M.W.R., Giles, G.G., Milne, R.L., McLean, C., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Hooning, M.J., Hollestelle, A., Martens, J.W.M., van den Ouweland, A.M.W., Marme, F., Schneeweiss, A., Yang, R., Burwinkel, B., Figueroa, J., Chanock, S.J., Lissowska, J., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Brenner, H., Butterbach, K., Holleczek, B., Kataja, V., Kosma, V-M., Hartikainen, J.M., Li, J., Brand, J.S., Humphreys, K., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Radice, P., Peterlongo, P., Manoukian, S., Ficarazzi, F., Beckmann, M.W., Hein, A., Ekici, A.B., Balleine, R., Phillips, K-A., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Jakubowska, A., Lubinski, J., Gronwald, J., Durda, K., Hamann, U., Kabisch, M., Ulmer, H.U., Ruediger, T., Margolin, S., Kristensen, V., Nord, S., Evans, D.G., Abraham, J., Earl, H., Poole, C.J., Hiller, L., Dunn, J.A., Bowden, S., Campa, D., Diver, W.R., Gapstur, S.M., Gaudet, M.M., Hankinson, S., Hoover, R.N., Husing, A., Kaaks, R., Machiela, M.J., Willett, W., Barrdahl, M., Canzian, F., Chin, S-F., Caldas, C., Hunter, D.J., Lindstrom, S., Garcia-Closas, M., Couch, F.J., Investigators, kConFab, Chenevix-Trench, G., Mannermaa, A., Andrulis, I.L., Hall, P., Chang-Claude, J., Easton, D.F., Bojesen, S.E., Cox, A., Fasching, P.A., Pharoah, P.D.P., Schmidt, M.K., and Investigators, NBCS
- Abstract
Introduction: Previous studies have identified common germline variants nominally associated with breast cancer\ud survival. These associations have not been widely replicated in further studies. The purpose of this study was to\ud evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled\ud analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association\ud Consortium.\ud Methods: A literature review was conducted of all previously published associations between common germline\ud variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival.\ud All associations that reached the nominal significance level of P value
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- 2015
23. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers
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Blanco, I., Kuchenbaecker, K., Cuadras, D., Wang, X.S., Barrowdale, D., Garibay, G.R., Librado, P., Sanchez-Gracia, A., Rozas, J., Bonifaci, N., McGuffog, L., Pankratz, V.S., Islam, A., Mateo, F., Berenguer, A., Petit, A., Catala, I., Brunet, J., Feliubadalo, L., Tornero, E., Benitez, J., Osorio, A., Cajal, T.R.Y., Nevanlinna, H., Aittomaki, K., Arun, B.K., Toland, A.E., Karlan, B.Y., Walsh, C., Lester, J., Greene, M.H., Mai, P.L., Nussbaum, R.L., Andrulis, I.L., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Barkardottir, R.B., Jakubowska, A., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Claes, K., Maerken, T. van, Diez, O., Hansen, T.V., Jonson, L., Gerdes, A.M., Ejlertsen, B., Hoya, M. de la, Caldees, T., Dunning, A.M., Oliver, C., Fineberg, E., Cook, M., Peock, S., McCann, E., Murray, A., Jacobs, C., Pichert, G., Lalloo, F., Chu, C., Dorkins, H., Paterson, J., Ong, K.R., Teixeira, M.R., Teixeira, Hogervorst, F.B.L., Hout, A.H. van der, Seynaeve, C., Luijt, R.B. van der, Ligtenberg, M.J.L., Devilee, P., Wijnen, J.T., Rookus, M.A., Meijers-Heijboer, H.E.J., Blok, M.J., Ouweland, A.M.W. van den, Aalfs, C.M., Rodriguez, G.C., Phillips, K.A.A., Piedmonte, M., Nerenstone, S.R., Bae-Jump, V.L., O'Malley, D.M., Ratner, E.S., Schmutzler, R.K., Wappenschmidt, B., Rhiem, K., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Plendl, H.J., Niederacher, D., Sutter, C., Wang-Gohrke, S., Steinemann, D., Preisler-Adams, S., Kast, K., Varon-Mateeva, R., Gehrig, A., Bojesen, A., Pedersen, I.S., Sunde, L., Jensen, U.B., Thomassen, M., Kruse, T.A., Foretova, L., Peterlongo, P., Bernard, L., Peissel, B., Scuvera, G., Manoukian, S., Radice, P., Ottini, L., Montagna, M., Agata, S., Maugard, C., Simard, J., Soucy, P., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Geschwantler-Kaulich, D., Tea, M.K., Pfeiler, G., John, E.M., Miron, A., Neuhausen, S.L., Terry, M.B., Chung, W.K., Daly, M.B., Goldgar, D.E., Janavicius, R., Dorfling, C.M., Rensburg, E.J. van, Fostira, F., Konstantopoulou, I., Garber, J., Godwin, A.K., Olah, E., Narod, S.A., Rennert, G., Paluch, S.S., Laitman, Y., Friedman, E., Liljegren, A., Rantala, J., Stenmark-Askmalm, M., Loman, N., Imyanitov, E.N., Hamann, U., Spurdle, A.B., Healey, S., Weitzel, J.N., Herzog, J., Margileth, D., Gorrini, C., Esteller, M., Gomez, A., Sayols, S., Vidal, E., Heyn, H., Stoppa-Lyonnet, Leone, M., Barjhoux, L., Fassy-Colcombet, M., Pauw, A. de, Lasset, C., Ferrer, S.F., Castera, L., Berthet, P., Cornelis, F., Bignon, Y.J., Damiola, F., Mazoyer, S., Sinilnikova, O.M., Maxwell, C.A., Vijai, J., Robson, M., Kauff, N., Corines, M.J., Villano, D., Cunningham, J., Lee, A., Lindor, N., Lazaro, C., Easton, D.F., Offit, K., Chenevix-Trench, G., Couch, F.J., Antoniou, A.C., Pujana, M.A., BCFR, SWE-BRCA, KConFab Investigators, GEMO, Human genetics, CCA - Oncogenesis, Medical Oncology, Clinical Genetics, Suzuki, Hiromu, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - Oncology, RS: GROW - R4 - Reproductive and Perinatal Medicine, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Department of Obstetrics and Gynecology, Clinicum, Medicum, Haartman Institute (-2014), and Department of Medical and Clinical Genetics
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single nucleotide ,Oncology ,Carcinogenesis ,TUBG1 ,Genes, BRCA2 ,Genes, BRCA1 ,Càncer d'ovari ,MODIFIERS ,Genome-wide association study ,Cell Cycle Proteins ,Breast cancer ,mammary glands ,Aetiology ,genes ,skin and connective tissue diseases ,Cancer ,Extracellular Matrix Proteins ,Hazard ratio ,CHIP-SEQ ,3. Good health ,ddc ,Hyaluronan Receptors ,Medicine ,Teixeira ,Human ,medicine.medical_specialty ,Evolution ,Science ,Non-P.H.S ,Single-nucleotide polymorphism ,Evolution, Molecular ,SDG 3 - Good Health and Well-being ,Ovarian cancer ,Genetics ,biochemistry ,Humans ,human ,CELL ,Polymorphism ,GENOME-WIDE ASSOCIATION ,medicine (all) ,Retrospective Studies ,Cancer och onkologi ,Prevention ,Mutació (Biologia) ,Biology and Life Sciences ,Molecular ,SWE-BRCA ,BRCA1 ,medicine.disease ,BRCA2 ,POLYMORPHISM ,Genes ,Genetic Loci ,Cancer and Oncology ,Mutation ,U.S. Gov't ,Bioinformatics ,medicine.disease_cause ,3123 Gynaecology and paediatrics ,Tubulin ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,ELEMENTS ,2.1 Biological and endogenous factors ,CD44 ,Non-U.S. Gov't ,Aurora Kinase A ,Likelihood Functions ,Multidisciplinary ,Research Support, Non-U.S. Gov't ,agricultural and biological sciences (all) ,genetics and molecular biology (all) ,BCFR ,Nuclear Proteins ,Single Nucleotide ,Mammary Glands ,SURVIVAL ,kConFab Investigators ,Female ,Microtubule-Associated Proteins ,Research Article ,Antigens, CD44 ,aurora kinase A ,breast neoplasms ,carcinogenesis ,cell cycle proteins ,estrogen receptor alpha ,evolution, molecular ,extracellular matrix proteins ,female ,genetic loci ,genetic predisposition to disease ,humans ,likelihood functions ,mammary glands, human ,microtubule-associated proteins ,nuclear proteins ,polymorphism ,retrospective studies ,tubulin ,genes, BRCA1 ,genes, BRCA2 ,mutation ,biochemistry, genetics and molecular biology (all) ,SUSCEPTIBILITY LOCI ,General Science & Technology ,3122 Cancers ,Breast Neoplasms ,Biology ,Research Support ,Polymorphism, Single Nucleotide ,N.I.H ,GENETIC INTERACTION NETWORKS ,Càncer de mama ,EXPRESSION SIGNATURE ,Amino acid sequence ,Research Support, N.I.H., Extramural ,Internal medicine ,Seqüència d'aminoàcids ,evolution ,Genetic variation ,Journal Article ,medicine ,Genetic Predisposition to Disease ,ddc:610 ,molecular ,Antigens ,Mammary Glands, Human ,ddc:611 ,Intramural ,Estrogen Receptor alpha ,Extramural ,Mutation (Biology) ,Research Support, N.I.H., Intramural ,3111 Biomedicine ,GEMO ,Research Support, U.S. Gov't, Non-P.H.S - Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values greater than 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. Funding Agencies|National Cancer Institute [UM1 CA164920]; Lithuania (BFBOCC-LT): Research Council of Lithuania grant [LIG-07/2012]; Hereditary Cancer Association (Paveldimo vezio asociacija); LSC grant [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepajas municipal council; Cancer Association of South Africa (CANSA); Morris and Horowitz Familes Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation (FMMA); COH-CCGCRN: City of Hope Clinical Cancer Genetics Community Network from the National Cancer Institute and the Office of the Director, National Institutes of Health; Hereditary Cancer Research Registry from the National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]; Fondazione IRCCS Istituto Nazionale Tumori; Cancer Research-United Kingdom grant [C12292/A11174, C1287/ A10118]; NHMRC Program Grant; DKFZ; European Union (European Social Fund-ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; European Social Fund; Cancer Research United Kingdom Grants [C1287/A10118, C1287/A11990]; National Institute of Health Research (NIHR) grant; NIHR grant; Royal Marsden NHS Foundation Trust; Cancer Research United Kingdom Grant [C5047/A8385]; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; AKG [5U01CA113916, R01CA140323]; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlonsen!" Award; Canadian Institutes of Health Research; Fund for Scientific Research Flanders (FWO); National Cancer Institute grant [CA 27469]; GOG Statistical and Data Center [CA 37517]; GOGs Cancer Prevention and Control Committee [CA 101165]; Intramural Research Program, NCI; ISCIII (Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society grant [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hungarian Research Grant [KTIA-OTKA CK-80745]; Norwegian EEA Financial Mechanism [HU0115/NA/2008-3/OP-9]; Spanish Ministry of Health ISCIII FIS [PI10/01422, PI12/01528, PI13/00285]; RTICC [RD12/0036/0008]; Ramon Areces (XV) Foundation; Eugenio Rodriguez Pascual Foundation; Roses Contra el Cancer Foundation; Spanish Association Against Cancer (AECC); AGAUR Generalitat de Catalunya [2009-SGR290, 2009-SGR293]; Polish Foundation of Science; Icelandic Association "Walking for Breast Cancer Research"; Nordic Cancer Union; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade-grant [PSR-SIIRI-701]; Ministero dellIstruzione, dellUniversita e della Ricerca and Ministero della Salute; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Foundation of Western Australia; Cancer Councils of Tasmania; National Institutes of Health grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; United States Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Jewish General Hospital Weekend; Quebec Ministry of Economic Development, Innovation and Export Trade; Cancer Councils of South Australia; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; MH CZ-DRO (MMCI) [00209805]; Niehaus Family Genetics Research Fund; STARR Cancer Consortium Grant; NAROD [1R01 CA149429-01]; NCI Intramural Research Program, National Institutes of Health [NO2-CP-11019-50, N02-CP-65504]; Westat, Inc, Rockville, Maryland; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York; Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant from the National Cancer Institute [UM1 CA164920]; Breast Cancer Family Registry (BCFR); United States Government or the BCFR; Ohio State University Comprehensive Cancer Center; Isreal cancer association; Israeli Inherited breast cancer consortium; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Womens Cancer Research Alliance; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Rooney Family Foundation; Susan G. Komen Foundation for the cure, Basser Research Center; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; SAF2010-20493; [PBZ_KBN_122/P05/2004]
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- 2015
24. Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
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Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, X, Barrowdale, D, De Garibay, GR, Librado, P, Sánchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Català, I, Brunet, J, Feliubadaló, L, Tornero, E, Benítez, J, Osorio, A, Teresa, R, Teresa, C, Nevanlinna, H, Aittomäki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Díez, O, Hansen, TV, Jønson, L, Gerdes, AM, Ejlertsen, B, De La Hoya, M, Caldés, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, T, Hogervorst, FBL, Van Der Hout, AH, Seynaeve, C, Van Der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, Van Den Ouweland, AMW, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, and Wang-Gohrke, S
- Subjects
skin and connective tissue diseases - Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4(false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteractionvalues > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
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- 2015
25. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2
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Orr, N., Dudbridge, F., Dryden, N., Maguire, S., Novo, D., Perrakis, E., Johnson, N., Ghoussaini, M., Hopper, J.L., Southey, M.C., Apicella, C., Stone, J., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Hogervorst, F.B., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Gibson, L., Aitken, Z., Warren, H., Sawyer, E., Tomlinson, I., Kerin, M.J., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina-Duverger, E., Sanchez, M., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Anton-Culver, H., Neuhausen, S.L., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Hamann, U., Brauch, H., Justenhoven, C., Bruning, T., Ko, Y.D., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Khan, S., Bogdanova, N., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Chenevix-Trench, G., Beesley, J., Lambrechts, D., Moisse, M., Floris, G., Beuselinck, B., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Peissel, B., Pensotti, V., Couch, F.J., Olson, J.E., Slettedahl, S., Vachon, C., Giles, G.G., Milne, R.L., McLean, C., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Kristensen, V., Alnaes, G.G., Nord, S., Borresen-Dale, A.L., Zheng, W., Deming-Halverson, S., Shrubsole, M., Long, J.R., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C.M., Asperen, C.J. van, Garcia-Closas, M., Figueroa, J., Chanock, S.J., Lissowska, J., Czene, K., Darabi, H., Eriksson, M., Klevebring, D., Hooning, M.J., Hollestelle, A., Deurzen, C.H.M. van, Kriege, M., Hall, P., Li, J.M., Liu, J.J., Humphreys, K., Cox, A., Cross, S.S., Reed, M.W.R., Pharoah, P.D.P., Dunning, A.M., Shah, M., Perkins, B.J., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Ashworth, A., Swerdlow, A., Jones, M., Schoemaker, M.J., Meindl, A., Schmutzler, R.K., Olswold, C., Slager, S., Toland, A.E., Yannoukakos, D., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Matsuo, K., Ito, H., Iwata, H., Ishiguro, J., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Teo, S.H., Yip, C.H., Kang, P., Ikram, M.K., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Hartman, M., Miao, H., Lim, W.Y., Lee, S.C., Sangrajrang, S., Gaborieau, V., Brennan, P., McKay, J., Wu, P.E., Hou, M.F., Yu, J.C., Shen, C.Y., Blot, W., Cai, Q.Y., Signorello, L.B., Luccarini, C., Bayes, C., Ahmed, S., Maranian, M., Healey, C.S., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Hunter, D.J., Lindstrom, S., Dennis, J., Michailidou, K., Bolla, M.K., Easton, D.F., Silva, I.D., Fletcher, O., Peto, J., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, Obstetrics & Gynecology, Medical Oncology, Pathology, Ophthalmology, Cardiothoracic Surgery, and Clinical Genetics
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Asian Continental Ancestry Group ,Adult ,Hepatocyte Nuclear Factor 3-alpha ,Risk ,binding ,European Continental Ancestry Group ,Kruppel-Like Transcription Factors ,estrogen-receptor-alpha ,Breast Neoplasms ,GATA3 Transcription Factor ,Polymorphism, Single Nucleotide ,White People ,Kruppel-Like Factor 4 ,Asian People ,SDG 3 - Good Health and Well-being ,Medizinische Fakultät ,common variants ,expression ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Genetic Association Studies ,Aged ,Association Studies Articles ,Estrogen Receptor alpha ,Chromosome Mapping ,foxa1 ,Middle Aged ,confer susceptibility ,analyses reveal ,Enhancer Elements, Genetic ,risk locus ,Genetic Loci ,functional variants ,genome-wide association ,Female ,Chromosomes, Human, Pair 9 - Abstract
We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis. ispartof: Human Molecular Genetics vol:24 issue:10 pages:2966-84 ispartof: location:England status: published
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- 2015
26. Identification of novel genetic markers of breast cancer survival
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Guo, Q, Schmidt, Mk, Kraft, P, Canisius, S, Chen, C, Khan, S, Tyrer, J, Bolla, Mk, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Kar, S, Beesley, J, Dunning, Am, Shah, M, Czene, K, Darabi, H, Eriksson, M, Lambrechts, D, Weltens, C, Leunen, K, Bojesen, Se, Nordestgaard, Bg, Nielsen, Sf, Flyger, H, Chang Claude, J, Rudolph, A, Seibold, P, Flesch Janys, D, Blomqvist, C, Aittomäki, K, Fagerholm, R, Muranen, Ta, Couch, Fj, Olson, Je, Vachon, C, Andrulis, Il, Knight, Ja, Glendon, G, Mulligan, Am, Broeks, A, Hogervorst, Fb, Haiman, Ca, Henderson, Be, Schumacher, F, Le Marchand, L, Hopper, Jl, Tsimiklis, H, Apicella, C, Southey, Mc, Cox, A, Cross, Ss, Reed, Mw, Giles, Gg, Milne, Rl, Mclean, C, Winqvist, R, Pylkäs, K, Jukkola Vuorinen, A, Grip, M, Hooning, Mj, Hollestelle, A, Martens, Jw, van den Ouweland, Am, Marme, F, Schneeweiss, A, Yang, R, Burwinkel, B, Figueroa, J, Chanock, Sj, Lissowska, J, Sawyer, Ej, Tomlinson, I, Kerin, Mj, Miller, N, Brenner, H, Dieffenbach, Ak, Arndt, V, Holleczek, B, Mannermaa, A, Kataja, V, Kosma, Vm, Hartikainen, Jm, Li, J, Brand, Js, Humphreys, K, Devilee, P, Tollenaar, Ra, Seynaeve, C, Radice, P, Peterlongo, P, Bonanni, B, Mariani, P, Fasching, Beckmann, Mw, Hein, A, Ekici, Ab, Chenevix Trench, G, Balleine, R, Kconfab, Investigators, Phillips, Ka, Benitez, J, Zamora, Mp, Arias Perez, Ji, Menéndez, P, Jakubowska, A, Lubinski, J, Jaworska Bieniek, K, Durda, K, Hamann, U, Kabisch, M, Ulmer, Hu, Rüdiger, T, Margolin, S, Kristensen, V, Nord, S, Evans, Dg, Abraham, Je, Earl, Hm, Hiller, L, Dunn, Ja, Bowden, S, Berg, C, Campa, Daniele, Diver, Wr, Gapstur, Sm, Gaudet, Mm, Hankinson, Se, Hoover, Rn, Hüsing, A, Kaaks, R, Machiela, Mj, Willett, W, Barrdahl, M, Canzian, F, Chin, Sf, Caldas, C, Hunter, Dj, Lindstrom, S, García Closas, M, Hall, P, Easton, Df, Eccles, Dm, Rahman, N, Nevanlinna, H, and Pharoah, P. d.
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GENOME-WIDE ASSOCIATION ,SINGLE-NUCLEOTIDE POLYMORPHISMS ,GENOTYPE IMPUTATION ,PROGNOSIS ,RISK ,LOCI ,CYCLOPHOSPHAMIDE ,METAANALYSIS ,PROGRESSION ,EPIRUBICIN - Published
- 2015
27. Refined histopathological predictors of BRCA1\ud and BRCA2 mutation status: a large-scale analysis\ud of breast cancer characteristics from the BCAC,\ud CIMBA, and ENIGMA consortia
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Spurdle, A.B., Couch, F.J., Parsons, M.T., McGuffog, L., Barrowdale, D., Bolla, M.K., Wang, Q., Healey, S., Schmutzler, R.K., Wappenschmidt, B., Rhiem, K., Hahnen, E., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Plendl, H., Niederacher, D., Sutter, C., Wang-Gohrke, S., Steinemann, D., Preisler-Adams, S., Kast, K., Varon-Mateeva, R., Ellis, S., Frost, D., Platte, R., Perkins, J., Evans, D.G., Izatt, L., Eeles, R., Adlard, J., Davidson, R., Cole, T., Scuvera, G., Manoukian, S., Bonanni, B., Mariette, F., Fortuzzi, S., Viel, A., Pasini, B., Papi, L., Varesco, L., Balleine, R., Nathanson, K.L., Domchek, S.M., Offitt, K., Jakubowska, A., Lindor, N., Thomassen, M., Jensen, U.B., Rantala, J., Borg, A., Andrulis, I.L., Miron, A., Hansen, T.V.O., Caldes, T., Neuhausen, S.L., Toland, A.E., Nevanlinna, H., Montagna, M., Garber, J., Godwin, A.K., Osorio, A., Factor, R.E., Terry, M.B., Rebbeck, T.R., Karlan, B.Y., Southey, M., Rashid, M.U., Tung, N., Pharoah, P.D.P., Blows, F.M., Dunning, A.M., Provenzano, E., Hall, P., Czene, K., Schmidt, M.K., Broeks, A., Cornelissen, S., Verhoef, S., Fasching, P.A., Beckmann, M.W., Ekici, A.B., Slamon, D.J., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Chang-Claude, J., Flesch-Janys, D., Rudolph, A., Seibold, P., Aittomaki, K., Muranen, T.A., Heikkila, P., Blomqvist, C., Figueroa, J., Chanock, S.J., Brinton, L., Lissowska, J., Olson, J.E., Pankratz, V.S., John, E.M., Whittemore, A.S., West, D.W., Hamann, U., Torres, D., Ulmer, H.U., Rudiger, T., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Van Asperen, C.J., Eccles, D.M., Tapper, W.J., Durcan, L., Jones, L., Peto, J., dos-Santos-Silva, I., Fletcher, O., Johnson, N., Dwek, M., Swann, R., Bane, A.L., Glendon, G., Mulligan, A.M., Giles, G.G., Milne, R.L., Baglietto, L., McLean, C., Carpenter, J., Clarke, C., Scott, R., Brauch, H., Bruning, T., Ko, Y-D., Cox, A., Cross, S.S., Reed, M.W.R., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Gronwald, J., Dork, T., Bogdanova, N., Park-Simon, T-W., Hillemanns, P., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Burwinkel, B., Marme, F., Surovy, H., Yang, R., Anton-Culver, H., Ziogas, A., Hooning, M.J., Collee, J.M., Martens, J.W.M., Tilanus-Linthorst, M.M.A., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Lindblom, A., Margolin, S., Joseph, V., Robson, M., Rau-Murthy, R., Gonzalez-Neira, A., Arias, J.I., Zamora, P., Benitez, J., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J.M., Peterlongo, P., Zaffaroni, D., Barile, M., Capra, F., Radice, P., Teo, S.H., Easton, D.F., Antoniou, A.C., Chenevix-Trench, G., Goldgar, D.E., Investigators, ABCTB, Group, EMBRACE, Network, GENICA, Group, HEBON, and Investigators, KConFab
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endocrine system diseases ,skin and connective tissue diseases - Abstract
Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline\ud mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have\ud utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of\ud uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of\ud Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological\ud predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical\ud modeling.\ud Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for\ud invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565\ud BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of\ud mutation status by histopathological markers were derived using a Mantel-Haenszel approach.\ud Results: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to\ud 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years\ud or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3\ud phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3\ud features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor\ud status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and\ud 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years\ud or older (LR = 1.79 (1.42 to 2.24)).\ud Conclusions: These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using\ud commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is\ud more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2\ud variant classification and inform patient mutation testing and clinical management.
- Published
- 2014
28. Primary Metabolite Chromatographic Profiling as a Tool for Chemotaxonomic Classification of Seeds from Berry Fruits
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Đurđa Krstić, Tomislav Tosti, Saša Đurović, Milica Fotirić Akšić, Boban Đorđević, Dušanka Milojković-Opsenica, Filip Andrić, and Jelena Trifković
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sugar, lipid and fatty acid identification ,chemical fingerprint ,berry seeds ,chromatography techniques ,Biotechnology ,TP248.13-248.65 ,Food processing and manufacture ,TP368-456 - Abstract
Research background. Considering the importance of consumption of berry fruits with proven health-beneficial properties and difficulties in quality control of products of specific botanical and geographic origin, a fingerprint method was developed, based on advanced data analysis (pattern recognition, classification), in order to relate the variability of nutrients in the selected cultivars to primary metabolite profile. Experimental approach. Forty-five samples of genuine berry fruit cultivars (strawberry, raspberry, blackberry, black currant, blueberry, gooseberry, chokeberry, cape gooseberry and goji berry) were characterized according to chromatographic profiles of primary metabolites (sugars, lipids and fatty acids) obtained by three chromatographic techniques (high-performance thin-layer chromatography, gas chromatography coupled to mass spectrometry, and high-performance anion-exchange chromatography with pulsed amperometric detection). Results and conclusions. Comprehensive analysis allowed monitoring and identification of metabolites belonging to polar lipids, mono-, di- and triacylglycerols, free fatty acids, free sterols, sterol esters, mono- to heptasaccharides and sugar alcohols. Chemical fingerprint of berry seeds showed the uniformity of primary metabolites within each fruit species, but revealed differences depending on the botanical origin. All three chromatographic methods provided a discriminative, informative and predictive metabolomics methodology, which proved to be useful for chemotaxonomic classification. Novelty and scientific contribution. A novel methodology for the identification of bioactive compounds from primary metabolites of natural products was described. The proposed untargeted metabolite profiling approach could be used in the future as a routine method for tracing of novel bioactive compounds. The knowledge of metabolite composition obtained in this study can provide a better assessment of genotypic and phenotypic differences between berry fruit species and varieties, and could contribute to the development of new breeding programs.
- Published
- 2022
- Full Text
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29. Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium
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Milne, R.L., Burwinkel, B., Michailidou, K., Arias-Perez, J.I., Zamora, M.P., Menendez-Rodriguez, P., Hardisson, D., Mendiola, M., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Dennis, J., Wang, Q., Bolla, M.K., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M., Ko, Y.D., Brauch, H., Hamann, U., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Matsuo, K., Ito, H., Iwata, H., Tajima, K., Li, J.M., Brand, J.S., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Lambrechts, D., Peuteman, G., Christiaens, M.R., Smeets, A., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Hartman, M., Hui, M., Lim, W.Y., Chan, C.W., Marme, F., Yang, R.X., Bugert, P., Lindblom, A., Margolin, S., Garcia-Closas, M., Chanock, S.J., Lissowska, J., Figueroa, J.D., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Hooning, M.J., Kriege, M., Ouweland, A.M.W. van den, Koppert, L.B., Fletcher, O., Johnson, N., Dos-Santos-Silva, I., Peto, J., Zheng, W., Deming-Halverson, S., Shrubsole, M.J., Long, J.R., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Cox, A., Cross, S.S., Reed, M.W.R., Schmidt, M.K., Broeks, A., Cornelissen, S., Braaf, L., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Simard, J., Dumont, M., Goldberg, M.S., Labreche, F., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Radice, P., Peterlongo, P., Azzollini, J., Barile, M., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Hopper, J.L., Schmidt, D.F., Makalic, E., Southey, M.C., Teo, S.H., Yip, C.H., Sivanandan, K., Tay, W.T., Shen, C.Y., Hsiung, C.N., Yu, J.C., Hou, M.F., Guenel, P., Truong, T., Sanchez, M., Mulot, C., Blot, W., Cai, Q.Y., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Bogdanova, N., Dork, T., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Shu, X.O., Lu, W., Gao, Y.T., Zhang, B., Couch, F.J., Toland, A.E., Yannoukakos, D., Sangrajrang, S., McKay, J., Wang, X.S., Olson, J.E., Vachon, C., Purrington, K., Severi, G., Baglietto, L., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Czene, K., Eriksson, M., Humphreys, K., Darabi, H., Ahmed, S., Shah, M., Pharoah, P.D.P., Hall, P., Giles, G.G., Benitez, J., Dunning, A.M., Chenevix-Trench, G., Easton, D.F., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, TNBCC, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
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Adult ,Ataxin-7 ,A Kinase Anchor Proteins ,Breast Neoplasms ,Nerve Tissue Proteins ,Middle Aged ,Protein Serine-Threonine Kinases ,Polymorphism, Single Nucleotide ,Cytoskeletal Proteins ,Case-Control Studies ,Humans ,NIMA-Related Kinases ,Female ,Genetic Predisposition to Disease ,health care economics and organizations ,Alleles ,Genome-Wide Association Study - Abstract
Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility\ud variants, although most studies have been underpowered to detect associations of a realistic magnitude.\ud We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which\ud evidence of association with breast cancer risk had been previously reported. Case-control data were combined\ud from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional\ud logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21\ud [rs1053338, per allele OR 5 1.07, 95% confidence interval (CI) 5 1.04–1.10, P 5 2.9 3 1026\ud ], AKAP9-M463I at\ud 7q21 (rs6964587, OR 5 1.05, 95% CI 5 1.03–1.07, P 5 1.7 3 1026\ud ) and NEK10-L513S at 3p24 (rs10510592,\ud OR 5 1.10, 95% CI 5 1.07 –1.12, P 5 5.1 3 10217). The first two associations reached genome-wide statistical\ud significance in a combined analysis of available data, including independent data from nine genome-wide association\ud studies (GWASs): for ATXN7-K264R, OR 5 1.07 (95% CI 5 1.05–1.10, P 5 1.0 3 1028\ud ); for AKAP9-M463I,\ud OR 5 1.05 (95% CI 5 1.04–1.07, P 5 2.0 3 10210). Further analysis of other common variants in these two\ud regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified\ud a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is\ud associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility\ud region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of\ud the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast\ud cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying\ud variants and the genes through which they act.
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- 2014
30. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study
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Johnson, N., Dudbridge, F., Orr, N., Gibson, L., Jones, M.E., Schoemaker, M.J., Folkerd, E.J., Haynes, B.P., Hopper, J.L., Southey, M.C., Dite, G.S., Apicella, C., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Atsma, F., Muir, K., Lophatananon, A., Fasching, P.A., Beckmann, M.W., Ekici, A.B., Renner, S.P., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina, E., Menegaux, F., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Milne, R., Zamora, M.P., Arias Perez, J.I., Benitez, J., Bernstein, L., Anton-Culver, H., Ziogas, A., Dur, C.C., Brenner, H., Mueller, H., Arndt, V., Dieffenbach, A.K., Meindl, A., Heil, J., Bartram, C.R., Schmutzler, R.K., Brauch, H., Justenhoven, C., Ko, Y-D., Nevanlinna, H., Muranen, T.A., Aittomaeki, K., Blomqvist, C., Matsuo, K., Doerk, T., Bogdanova, NV., Antonenkova, N.N., Lindblom, A., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J.M., Chenevix-Trench, G., Beesley, J., Wu, A.H., Van den Berg, D., Tseng, C-C., Lambrechts, D., Smeets, D., Neven, P., Wildiers, H., Chang-Claude, J., Rudolph, A., Nickels, S., Flesch-Janys, D., Radice, P., Peterlongo, P., Bonanni, B., Pensotti, V., Couch, F.J., Olson, J.E., Wang, X., Fredericksen, Z., Pankratz, V.S., Giles, G.G., Severi, G., Baglietto, L., Haiman, C., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Soucy, P., Teo, S., Yip, C.H., Phuah, S.Y., Cornes, B.K., Kristensen, V.N., Alnaes, G.G., Borresen-Dale, A-L., Zheng, W., Winqvist, R., Pylkaes, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L, Knight, J.A., Glendon, G., Mulligan, A.M., Devillee, P., Figueroa, J., Chanock, S.J., Lissowska, J., Sherman, M.E., Hall, P., Schoof, N., Hooning, M., Hollestelle, A., Oldenburg, R.A., Tilanus-Linthorst, M., Liu, J., Cox, A., Brock, I.W., Reed, M.W.R., Cross, S.S., Blot, W., Signorello, L.B., Pharoah, P.D.P., Dunning, A.M., Shah, M., Kang, D., Noh, D-Y., Park, S.K., Choi, J-Y., Hartman, M., Miao, H., Lim, W.Y., Tang, A., Hamann, U., Foersti, A., Ruediger, T., Ulmer, H.U., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Slager, S., Toland, A.E., Vachon, C., Yannoukakos, D., Shen, C-Y., Yu, J-C., Huang, C-S., Hou, M-F., Gonzalez-Neira, A., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Dennis, J., Michailidou, K., Bolla, M.K., Wang, J., Easton, D.F., Garcia-Closas, M., Dowsett, M., Ashworth, A., Swerdlow, A.J., Peto, J., Silva, I.D.S., Fletcher, O., Breast, G.E.I., Investigators, K., Grp, AOCS, Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Dennis, Joe [0000-0003-4591-1214], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
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Adult ,Menarche ,Genotype ,Age Factors ,Breast Neoplasms ,Middle Aged ,Polymorphism, Single Nucleotide ,White People ,Premenopause ,Risk Factors ,Cytochrome P-450 CYP3A ,Humans ,Female ,Genetic Predisposition to Disease ,Age of Onset ,Reproductive History ,Genetic Association Studies ,Aged - Abstract
Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to\ud the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and\ud a modest reduction in risk of breast cancer in women age ≤50 years.\ud Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of\ud 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping\ud of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine\ud whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.\ud Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found\ud no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were\ud OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (Ptrend = 0.02). There was\ud no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche\ud in controls (Ptrend = 0.005) but not cases (Ptrend = 0.97). Consequently the association between rs10235235 and breast\ud cancer risk differed according to age at menarche (Phet = 0.02); the rare allele of rs10235235 was associated with a\ud reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94;\ud ORhom = 0.81, 95% CI 0.51, 1.30; Ptrend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06,\ud 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; Ptrend = 0.29).\ud Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both\ud breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche\ud and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.
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- 2014
31. Genetic Predisposition to In Situ and Invasive Lobular\ud Carcinoma of the Breast
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Sawyer, E., Roylance, R., Petridis, C., Brook, M.N., Nowinski, S., Papouli, E., Fletcher, O., Pinder, S., Hanby, A., Kohut, K., Gorman, P., Caneppele, M., Peto, J., Silva, I.D.S., Johnson, N., Swann, R., Dwek, M., Perkins, K-A., Gillett, C., Houlston, R., Ross, G., De Ieso, P., Southey, M.C., Hopper, J.L., Provenzano, E., Apicella, C., Wesseling, J., Cornelissen, S., Keeman, R., Fasching, P.A., Jud, S.M., Ekici, A.B., Beckmann, M.W., Kerin, M.J., Marme, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Truong, T., Laurent-Puig, P., Kerbrat, P., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Milne, R.L., Perez, J.I.A., Menendez, P., Benitez, J., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Meindl, A., Lichtner, P., Schmutzler, R.K., Lochmann, M., Brauch, H., Fischer, H-P., Ko, Y-D., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Bogdanova, N.V., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J.M., Chenevix-Trench, G., Lambrechts, D., Weltens, C., Van Limbergen, E., Hatse, S., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Bonanni, B., Volorio, S., Giles, G.G., Severi, G., Baglietto, L., Mclean, C.A., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Kristensen, V., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Devillee, P., Tollenaar, R.A.E.M., Seynaeve, C.M., Kriege, M., Figueroa, J., Chanock, S.J., Sherman, M.E., Hooning, M.J., Hollestelle, A., van den Ouweland, A.M.W., van Deurzen, C.H.M., Li, J., Czene, K., Humphreys, K., Cox, A., Cross, S.S., Reed, M.W.R., Shah, M., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M., Couch, F.J., Hallberg, E., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Tessier, D.C., Vincent, D., Bacot, F., Bolla, M.K., Wang, Q., Dennis, J., Michailidou, K., Dunning, A.M., Hall, P., Easton, D., Pharoah, P., Schmidt, M.K., Tomlinson, I., Garcia-Closas, M., Network, GENICA, and Investigators, K
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body regions ,skin and connective tissue diseases - Abstract
Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and\ud often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common\ud polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To\ud identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure\ud LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/\ud LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses\ud identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0610210; P-het for ILC vs IDC\ud ER+ tumors = 1.861024\ud ). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and\ud 15 with LCIS at P,0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, Phet\ud = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/\ud LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences\ud between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11,\ud rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/\ud 14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast\ud cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms\ud predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although\ud there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but\ud distinct etiological pathways within ER+ breast cancer between morphological subtypes.
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- 2014
32. A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium
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Rl, Milne, Herranz J, Michailidou K, Joe Dennis, Jp, Tyrer, Mp, Zamora, Ji, Arias-Perez, González-Neira A, Pita G, Alonso MR, Wang Q, Mk, Bolla, Czene K, Eriksson M, Humphreys K, Darabi H, Li J, Anton-Culver H, Sl, Neuhausen, Ziogas A, Ca, Clarke, Jl, Hopper, Gs, Dite, Apicella C, Mc, Southey, Chenevix-Trench G, kConFab Investigators, Australian Ovarian Cancer Study Group, Swerdlow A, Ashworth A, Orr N, Schoemaker M, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Il, Andrulis, Ja, Knight, Glendon G, Am, Mulligan, Se, Bojesen, Bg, Nordestgaard, Flyger H, Nevanlinna H, Ta, Muranen, Aittomäki K, Blomqvist C, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Wang X, Je, Olson, Vachon C, Purrington K, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Am, Dunning, Shah M, Guénel P, Truong T, Sanchez M, Mulot C, Brenner H, Ak, Dieffenbach, Arndt V, Stegmaier C, Lindblom A, Margolin S, Hooning M, Hollestelle A, Collée M, Jager A, Cox A, Iw, Brock, Mw, Reed, Devilee P, Ra, Tollenaar, Seynaeve C, Ca, Haiman, Be, Henderson, Schumacher F, Le Marchand L, Simard J, Dumont M, Soucy P, Dörk T, Nv, Bogdanova, Hamann U, Försti A, Rüdiger T, Hu, Ulmer, Pa, Fasching, Häberle L, Ab, Ekici, Mw, Beckmann, Fletcher O, Johnson N, Id, Silva, Peto J, Radice P, Peterlongo P, Peissel B, Mariani P, Gg, Giles, Severi G, Baglietto L, Sawyer E, Tomlinson I, Kerin M, Miller N, Marme F, Burwinkel B, Mannermaa A, Kataja V, Vm, Kosma, Hartikainen J, Lambrechts D, Bt, Yesilyurt, Floris G, Leunen K, Gg, Alnæs, Kristensen V, Al, Børresen-Dale, García-Closas M, Sj, Chanock, Lissowska J, Jd, Figueroa, Mk, Schmidt, Broeks A, Verhoef S, Ej, Rutgers, Brauch H, Brüning T, Yd, Ko, Genica, The Network, Fj, Couch, Ae, Toland, Tnbcc, The, Yannoukakos D, Pd, Pharoah, Hall P, Benítez J, Malats N, and Df, Easton
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Australian Ovarian Cancer Study Group ,Genetics & Heredity ,Breast Neoplasms ,Epistasis, Genetic ,Biological Sciences ,TNBCC ,Polymorphism, Single Nucleotide ,Medical and Health Sciences ,Logistic Models ,Case-Control Studies ,kConFab Investigators ,Humans ,Genetic Predisposition to Disease ,Female ,GENICA Network ,Genome-Wide Association Study - Abstract
Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10(-4)) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10(-8). Results from the second analytic approach were consistent with those from the first (P > 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.
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- 2014
33. MicroRNA related polymorphisms and breast cancer risk
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Khan, S., Greco, D., Michailidou, K., Milne, R.L., Muranen, T.A., Heikkinen, T., Aaltonen, K., Dennis, J., Bolla, M.K., Liu, J., Hall, P., Irwanto, A., Humphreys, K., Li, J., Czene, K., Chang-Claude, J., Hein, R., Rudolph, A., Seibold, P., Flesch-Janys, D., Fletcher, O., Peto, J., Silva, I.D., Johnson, N., Gibson, L., Aitken, Z., Hopper, J.L., Tsimiklis, H., Bui, M., Makalic, E., Schmidt, D.F., Southey, M.C., Apicella, C., Stone, J., Waisfisz, Q., Meijers-Heijboer, H., Adank, M.A., Luijt, R.B. van der, Meindl, A., Schmutzler, R.K., Muller-Myhsok, B., Lichtner, P., Turnbull, C., Rahman, N., Chanock, S.J., Hunter, D.J., Cox, A., Cross, S.S., Reed, M.W.R., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Hogervorst, F.B., Fasching, P.A., Schrauder, M.G., Ekici, A.B., Beckmann, M.W., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Benitez, J., Zamora, P.M., Perez, J.I.A., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Pharoah, P.D.P., Dunning, A.M., Shah, M., Luben, R., Brown, J., Couch, F.J., Wang, X., Vachon, C., Olson, J.E., Lambrechts, D., Moisse, M., Paridaens, R., Christiaens, M.R., Guenel, P., Truong, T., Laurent-Puig, P., Mulot, C., Marme, F., Burwinkel, B., Schneeweiss, A., Sohn, C., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Andrulis, I.L., Knight, J.A., Tchatchou, S., Mulligan, A.M., Dork, T., Bogdanova, N.V., Antonenkova, N.N., Anton-Culver, H., Darabi, H., Eriksson, M., Garcia-Closas, M., Figueroa, J., Lissowska, J., Brinton, L., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Kristensen, V.N., Slager, S., Toland, A.E., Ambrosone, C.B., Yannoukakos, D., Lindblom, A., Margolin, S., Radice, P., Peterlongo, P., Barile, M., Mariani, P., Hooning, M.J., Martens, J.W.M., Collee, J.M., Jager, A., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Giles, G.G., McLean, C., Brauch, H., Bruning, T., Ko, Y.D., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Swerdlow, A., Ashworth, A., Orr, N., Jones, M., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Kataja, V., Kosma, V.M., Hartikainen, J.M., Mannermaa, A., Hamann, U., Chenevix-Trench, G., Blomqvist, C., Aittomaki, K., Easton, D.F., Nevanlinna, H., KConFab Investigators, Australian Ovarian Canc Study Grp, GENICA Network, Department of Obstetrics and Gynecology, Clinicum, Department of Oncology, Haartman Institute (-2014), Department of Medical and Clinical Genetics, HUS Gynecology and Obstetrics, Human genetics, CCA - Oncogenesis, Obstetrics & Gynecology, Medical Oncology, Erasmus MC other, and Clinical Genetics
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Heredity ,IDENTIFIES 3 ,lcsh:Medicine ,Estrogen receptor ,Genome-wide association study ,Bioinformatics ,3123 Gynaecology and paediatrics ,HUMAN GENES ,lcsh:Science ,3' Untranslated Regions ,Multidisciplinary ,Research Support, Non-U.S. Gov't ,Chromosome Mapping ,SINGLE-NUCLEOTIDE POLYMORPHISMS ,3. Good health ,Receptors, Estrogen ,Female ,CASP8 GENE ,Research Article ,EXPRESSION ,Genotype ,SUSCEPTIBILITY LOCI ,education ,3122 Cancers ,MiRNA binding ,Single-nucleotide polymorphism ,Breast Neoplasms ,Biology ,Genetic Predisposition ,Polymorphism, Single Nucleotide ,BINDING-SITES ,Breast cancer ,REDUCED RISK ,Research Support, N.I.H., Extramural ,SDG 3 - Good Health and Well-being ,microRNA ,Genetic predisposition ,medicine ,Journal Article ,Genetics ,Cancer Genetics ,Humans ,GENOME-WIDE ASSOCIATION ,Drosha ,Genetic Association Studies ,Binding Sites ,Complex Traits ,lcsh:R ,Biology and Life Sciences ,Computational Biology ,Human Genetics ,medicine.disease ,Research Support, N.I.H., Intramural ,COMMON VARIANT ,MicroRNAs ,Case-Control Studies ,Genetics of Disease ,lcsh:Q ,Research Support, U.S. Gov't, Non-P.H.S ,Genome-Wide Association Study - Abstract
Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95 confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95 CI: 0.95-0.99), rs10719 (OR 0.97; 95 Cl: 0.94-0.99), rs4687554 (OR 0.97; 95 CI: 0.95-0.99, and rs3134615 (OR 1.03; 95 CI: 1.01 -1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. This is an open-access article free of all copyright.
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- 2014
34. Large-scale genotyping identifies 41 new loci associated with breast cancer risk
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Michailidou, K., Hall, P., Gonzalez-Neira, A., Ghoussaini, M., Dennis, J., Milne, R.L., Schmidt, M.K., Chang-Claude, J., Bojesen, S.E., Bolla, M.K., Wang, Q., Dicks, E., Lee, A., Turnbull, C., Rahman, N., Fletcher, O., Peto, J., Gibson, L., Silva, I.D., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Czene, K., Irwanto, A., Liu, J.J., Waisfisz, Q., Meijers-Heijboer, H., Adank, M., Luijt, R.B. van der, Hein, R., Dahmen, N., Beckman, L., Meindl, A., Schmutzler, R.K., Muller-Myhsok, B., Lichtner, P., Hopper, J.L., Southey, M.C., Makalic, E., Schmidt, D.F., Uitterlinden, A.G., Hofman, A., Hunter, D.J., Chanock, S.J., Vincent, D., Bacot, F., Tessier, D.C., Canisius, S., Wessels, L.F.A., Haiman, C.A., Shah, M., Luben, R., Brown, J., Luccarini, C., Schoof, N., Humphreys, K., Li, J.M., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Couch, F.J., Wang, X.S., Vachon, C., Stevens, K.N., Lambrechts, D., Moisse, M., Paridaens, R., Christiaens, M.R., Rudolph, A., Nickels, S., Flesch-Janys, D., Johnson, N., Aitken, Z., Aaltonen, K., Heikkinen, T., Broeks, A., Van't Veer, L.J., Schoot, C.E. van der, Guenel, P., Truong, T., Laurent-Puig, P., Menegaux, F., Marme, F., Schneeweiss, A., Sohn, C., Burwinke, B., Zamora, M.P., Perez, J.I.A., Pita, G., Alonso, M.R., Cox, A., Brock, I.W., Cross, S.S., Reed, M.W.R., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Henderson, B.E., Schumacher, F., Marchand, L. le, Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Lindblom, A., Margolin, S., Hooning, M.J., Hollestelle, A., Ouweland, A.M.W. van den, Jager, A., Bui, Q.M., Stone, J., Dite, G.S., Apicella, C., Tsimiklis, H., Giles, G.G., Severi, G., Baglietto, L., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Brenner, H., Muller, H., Arndt, V., Stegmaier, C., Swerdlown, A., Ashworth, A., Orr, N., Jones, M., Figueroa, J., Lissowska, J., Brinton, L., Goldberg, M.S., Labreche, F., Dumont, M., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Brauch, H., Hamann, U., Bruning, T., Radice, P., Peterlongo, P., Manouldan, S., Bonanni, B., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Bogdanova, N.V., Antonenkova, N.N., Dork, T., Kristensen, V.N., Anton-Culver, H., Slager, S., Toland, A.E., Edge, S., Fostira, F., Kang, D., Yoo, K.Y., Noh, D.Y., Matsuo, K., Ito, H., Iwata, H., Sueta, A., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Teo, S.H., Yip, C.H., Phuah, S.Y., Cornes, B.K., Hartman, M., Miao, H., Lim, W.Y., Sng, J.H., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Shen, C.Y., Hsiung, C.N., Wu, P.E., Ding, S.L., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Blot, W.J., Signorello, L.B., Cai, Q.Y., Zheng, W., Deming-Halverson, S., Shrubsole, M., Long, J.R., Simard, J., Garcia-Closas, M., Pharoah, P.D.P., Chenevix-Trench, G., Dunning, A.M., Benitez, J., Easton, D.F., Breast Ovarian Canc Susceptibility, Hereditary Breast Ovarian Canc Res, kConFab Investigators, Australian Ovarian Can Study Grp, GENICA Gene Environm Interaction B, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Landsteiner Laboratory, Clinical Haematology, Clinical Genetics, Internal Medicine, Epidemiology, Medical Oncology, Cardiothoracic Surgery, Human genetics, CCA - Oncogenesis, and ~
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signaling pathway ,Genotyping ,Genotype ,Single-nucleotide polymorphism ,Genome-wide association study ,Breast Neoplasms ,consortium ,Biology ,Case-Control Studies ,Cooperative Behavior ,Female ,Gene-Environment Interaction ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Meta-Analysis as Topic ,Polymorphism, Single Nucleotide ,Risk Factors ,Genetic Predisposition to Disease ,Genetics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,SDG 3 - Good Health and Well-being ,common variants ,expression ,medicine ,Polymorphism ,gene ,hormone-related protein ,030304 developmental biology ,Genetic association ,0303 health sciences ,Breast cancer susceptibility ,Cancer ,Single Nucleotide ,medicine.disease ,confer susceptibility ,susceptibility loci ,3. Good health ,14q24.1 rad51l1 ,TOX3 ,030220 oncology & carcinogenesis ,genome-wide association - Abstract
Journal article Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10!¿8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. European Community Seventh Framework Programme - grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) peer-reviewed
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- 2013
35. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
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Couch, Fergus J., Xianshu, Wang, Lesley, Mcguffog, Andrew, Lee, Curtis, Olswold, Kuchenbaecker, Karoline B., Penny, Soucy, Zachary, Fredericksen, Daniel, Barrowdale, Joe, Dennis, Gaudet, Mia M., Dicks, Ed, Matthew, Kosel, Sue, Healey, Sinilnikova, Olga M., Adam, Lee, François, Bacot, Daniel, Vincent, Hogervorst, Frans B. L., Susan, Peock, Dominique Stoppa Lyonnet, Anna, Jakubowska, Paolo, Radice, Rita Katharina Schmutzler, Domchek, S. M., Piedmonte, M., Singer, C. F., Friedman, E., Thomassen, M., Hansen, T. V. O., Neuhausen, S. L., Szabo, C. I., Blanco, I., Greene, M. H., Karlan, B. Y., Garber, J., Phelan, C. M., Weitzel, J. N., Montagna, M., Olah, E., Andrulis, I. L., Godwin, A. K., Yannoukakos, D., Goldgar, D. E., Caldes, T., Nevanlinna, H., Osorio, A., Terry, M. B., Daly, M. B., Van Rensburg, E. J., Hamann, U., Ramus, S. J., Ewart Toland, A., Caligo, M. A., Olopade, O. I., Tung, N., Claes, K., Beattie, M. S., Southey, M. C., Imyanitov, E. N., Tischkowitz, M., Janavicius, R., John, E. M., Kwong, A., Diez, O., Balmana, J., Barkardottir, R. B., Arun, B. K., Rennert, G., Teo, S. H., Ganz, P. A., Campbell, I., Van Der Hout, A. H., Van Deurzen, C. H. M., Seynaeve, C., Gomez Garcia, E. B., Van Leeuwen, F. E., Meijers Heijboer, H. E. J., Gille, J. J. P., Ausems, M. G. E. M., Blok, M. J., Ligtenberg, M. J. L., Rookus, M. A., Devilee, P., Verhoef, S., Van Os, T. A. M., Wijnen, J. T., Frost, D., Ellis, S., Fineberg, E., Platte, R., Evans, D. G., Izatt, L., Eeles, R. A., Adlard, J., Eccles, D. M., Cook, J., Brewer, C., Douglas, F., Hodgson, S., Morrison, P. J., Side, L. E., Donaldson, A., Houghton, C., Rogers, M. T., Dorkins, H., Eason, J., Gregory, H., Mccann, E., Murray, A., Calender, A., Hardouin, A., Berthet, P., Delnatte, C., Nogues, C., Lasset, C., Houdayer, C., Leroux, D., Rouleau, E., Prieur, F., Damiola, F., Sobol, H., Coupier, I., Venat Bouvet, L., Castera, L., Gauthier Villars, M., Leone, M., Pujol, P., Mazoyer, S., Bignon, Y. J., Zlowocka Perlowska, E., Gronwald, J., Lubinski, J., Durda, K., Jaworska, K., Huzarski, T., Spurdle, A. B., Viel, A., Peissel, B., Bonanni, B., Melloni, G., Ottini, Laura, Papi, L., Varesco, L., Tibiletti, M. G., Peterlongo, P., Volorio, S., Manoukian, S., Pensotti, V., Arnold, N., Engel, C., Deissler, H., Gadzicki, D., Gehrig, A., Kast, K., Rhiem, K., Meindl, A., Niederacher, D., Ditsch, N., Plendl, H., Preisler Adams, S., Engert, S., Sutter, C., Varon Mateeva, R., Wappenschmidt, B., Weber, B. H. F., Arver, B., Stenmark Askmalm, M., Loman, N., Rosenquist, R., Einbeigi, Z., Nathanson, K. L., Rebbeck, T. R., Blank, S. V., Cohn, D. E., Rodriguez, G. C., Small, L., Friedlander, M., Bae Jump, V. L., Fink Retter, A., Rappaport, C., Gschwantler Kaulich, D., Pfeiler, G., Tea, M. K., Lindor, N. M., Kaufman, B., Shimon Paluch, S., Laitman, Y., Skytte, A. B., Gerdes, A. M., Pedersen, I. S., Moeller, S. T., Kruse, T. A., Jensen, U. B., Vijai, J., Sarrel, K., Robson, M., Kauff, N., Mulligan, A. M., Glendon, G., Ozcelik, H., Ejlertsen, B., Nielsen, F. C., Jonson, L., Andersen, M. K., Ding, Y. C., Steele, L., Foretova, L., Teule, A., Lazaro, C., Brunet, J., Pujana, M. A., Mai, P. L., Loud, J. T., Walsh, C., Lester, J., Orsulic, S., Narod, S. A., Herzog, J., Sand, S. R., Tognazzo, S., Agata, S., Vaszko, T., Weaver, J., Stavropoulou, A. V., Buys, S. S., Romero, A., De La Hoya, M., Aittomaki, K., Muranen, T. A., Duran, M., Chung, W. K., Lasa, A., Dorfling, C. M., Miron, A., Benitez, J., Senter, L., Huo, D., Chan, S. B., Sokolenko, A. P., Chiquette, J., Tihomirova, L., Friebel, T. M., Agnarsson, B. A., K. H., Lu, Lejbkowicz, F., James, P. A., Hall, P., Dunning, A. M., Tessier, D., Cunningham, J., Slager, S. L., Wang, C., Hart, S., Stevens, K., Simard, J., Pastinen, T., Pankratz, V. S., Offit, K., Easton, D. F., Chenevix Trench, G., Antoniou, A. C., Thorne, H., Niedermayr, E., Borg, A., Olsson, H., Jernstrom, H., Henriksson, K., Harbst, K., Soller, M., Kristoffersson, U., Ofverholm, A., Nordling, M., Karlsson, P., Von Wachenfeldt, A., Liljegren, A., Lindblom, A., Bustinza, G. B., Rantala, J., Melin, B., Ardnor, C. E., Emanuelsson, M., Ehrencrona, H., Pigg, M. H., Liedgren, S., Hogervorst, F. B. L., Schmidt, M. K., De Lange, J., Collee, J. M., Van Den Ouweland, A. M. W., Hooning, M. J., Van Asperen, C. J., Tollenaar, R. A., Van Cronenburg, T. C. T. E. F., Kets, C. M., Mensenkamp, A. R., Van Der Luijt, R. B., Aalfs, C. M., Waisfisz, Q., Oosterwijk, J. C., Van Der Hout, H., Mourits, M. J., De Bock, G. H., Peock, S., Miedzybrodzka, Z., Morrison, P., Jeffers, L., Cole, T., Ong, K. R., Hoffman, J., James, M., Paterson, J., Taylor, A., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Kivuva, E., Searle, A., Goodman, S., Hill, K., Davidson, R., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Brady, A., Melville, A., Randhawa, K., Barwell, J., Serra Feliu, G., Ellis, I., Lalloo, F., Taylor, J., Side, L., Male, A., Berlin, C., Collier, R., Claber, O., Jobson, I., Walker, L., Mcleod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Stormorken, A., Bancroft, E., Page, E., Ardern Jones, A., Kohut, K., Wiggins, J., Castro, E., Killick, E., Martin, S., Rea, G., Kulkarni, A., Quarrell, O., Bardsley, C., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Lehmann, A., Eccles, D., Lucassen, A., Crawford, G., Mcbride, D., Smalley, S., Sinilnikova, O., Barjhoux, L., Verny Pierre, C., Giraud, S., Stoppa Lyonnet, D., Buecher, B., Moncoutier, V., Belotti, M., Tirapo, C., De Pauw, A., Bressac De Paillerets, B., Caron, O., Uhrhammer, N., Bonadona, V., Handallou, S., Bourdon, V., Noguchi, T., Remenieras, A., Eisinger, F., Peyrat, J. P., Fournier, J., Revillion, F., Vennin, P., Adenis, C., Lidereau, R., Demange, L., Muller, D., Fricker, J. P., Barouk Simonet, E., Bonnet, F., Bubien, V., Sevenet, N., Longy, M., Toulas, C., Guimbaud, R., Gladieff, L., Feillel, V., Dreyfus, H., Rebischung, C., Peysselon, M., Coron, F., Faivre, L., Lebrun, M., Kientz, C., Ferrer, S. F., Frenay, M., Mortemousque, I., Coulet, F., Colas, C., Soubrier, F., Sokolowska, J., Bronner, M., Lynch, H. T., Snyder, C. L., Angelakos, M., Maskiell, J., Dite, G., MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - School for Oncology and Reproduction, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Kastler Brossel (LKB (Jussieu)), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Generalitat de Catalunya, Asociación Española Contra el Cáncer, Fundación Ramón Areces, Instituto de Salud Carlos III, Clinical Genetics, Pathology, Medical Oncology, Pediatric Surgery, Department of Obstetrics and Gynecology, Clinicum, Department of Medical and Clinical Genetics, HUS Gynecology and Obstetrics, Epidemiology and Data Science, Human genetics, CCA - Oncogenesis, Universitat de Barcelona, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, and Human Genetics
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SELECTION ,Oncology ,Cancer Research ,Medicin och hälsovetenskap ,endocrine system diseases ,[SDV]Life Sciences [q-bio] ,610 Medizin ,Càncer d'ovari ,SUSCEPTIBILITY ALLELES ,MODIFIERS ,ComputingMilieux_LEGALASPECTSOFCOMPUTING ,Genome-wide association study ,QH426-470 ,Medical and Health Sciences ,SUBTYPES ,Breast cancer ,0302 clinical medicine ,Human genetics ,3123 Gynaecology and paediatrics ,Risk Factors ,GENETIC-VARIANTS ,Genotype ,Naturvetenskap ,Malalties hereditàries ,INVESTIGATORS ,skin and connective tissue diseases ,ComputingMilieux_MISCELLANEOUS ,Genetics (clinical) ,POPULATION ,Ovarian Neoplasms ,Genetics ,Subtypes ,ddc:610 ,0303 health sciences ,education.field_of_study ,Genètica humana ,Susceptibility alleles ,BRCA1 Protein ,COMMON VARIANTS ,Breast Cancer Epidemiology ,Middle Aged ,Prognosis ,BRCA2 Protein ,3. Good health ,030220 oncology & carcinogenesis ,Female ,Natural Sciences ,Genetic diseases ,Heterozygote ,medicine.medical_specialty ,Znf365 ,education ,3122 Cancers ,Population ,Breast Neoplasms ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Càncer de mama ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Ovarian cancer ,Translational research [ONCOL 3] ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetics and epigenetic pathways of disease Translational research [NCMLS 6] ,Molecular Biology ,Selection ,ddc:614 ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,Common variants ,CONSORTIUM ,Modifiers ,Biology and Life Sciences ,BRCA1 ,medicine.disease ,R1 ,Genetic-variants ,Cancer and Oncology ,Mutation ,Investigators ,3111 Biomedicine ,ZNF365 ,Consortium ,Genome-Wide Association Study - Abstract
This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- CIMBA et al., BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers., The study was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341), grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure; Cancer Research UK grants C12292/A11174 and C1287/A10118; the European Commission's Seventh Framework Programme grant agreement 223175 (HEALTH-F2-2009-223175). Breast Cancer Family Registry Studies (BCFR): supported by the National Cancer Institute, National Institutes of Health under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute of California (U01 CA69417), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), and University of Melbourne (U01 CA69638). The Australian BCFR was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. Melissa C. Southey is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. Carriers at FCCC were also identified with support from National Institutes of Health grants P01 CA16094 and R01 CA22435. The New York BCFR was also supported by National Institutes of Health grants P30 CA13696 and P30 ES009089. The Utah BCFR was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH grant UL1 RR025764, and by Award Number P30 CA042014 from the National Cancer Institute. Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC): BFBOCC is partly supported by Lithuania (BFBOCC-LT), Research Council of Lithuania grant LIG-19/2010, and Hereditary Cancer Association (Paveldimo vėžio asociacija)., Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF Nr.2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016.BRCA-gene mutations and breast cancer in South African women (BMBSA): BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. Beckman Research Institute of the City of Hope (BRICOH): Susan L. Neuhausen was partially supported by the Morris and Horowitz Families Endowed Professorship. BRICOH was supported by NIH R01CA74415 and NIH P30 CA033752. Copenhagen Breast Cancer Study (CBCS): The CBCS study was supported by the NEYE Foundation. Spanish National Cancer Centre (CNIO): This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrileña Foundation (FMMA) and SAF2010-20493. City of Hope Cancer Center (COH): The City of Hope Clinical Cancer Genetics Community Research Network is supported by Award Number RC4A153828 (PI: Jeffrey N. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella (CONSIT TEAM): CONSIT TEAM was funded by grants from Fondazione Italiana per la Ricerca sul Cancro (Special Project “Hereditary tumors”), Italian Association for Cancer Research (AIRC, IG 8713), Italian Minitry of Health (Extraordinary National Cancer Program 2006, “Alleanza contro il Cancro” and “Progetto Tumori Femminili), Italian Ministry of Education, University and Research (Prin 2008) Centro di Ascolto Donne Operate al Seno (CAOS) association and by funds from Italian citizens who allocated the 5×1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5×1000’). German Cancer Research Center (DKFZ): The DKFZ study was supported by the DKFZ. The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON): HEBON is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the NWO grant 91109024, the Pink Ribbon grant 110005, and the BBMRI grant CP46/NWO., Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE): EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. 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. Rosalind A. Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Fox Chase Cancer Canter (FCCC): The authors acknowledge support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. Andrew K. Godwin was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC): The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers (GEMO): The GEMO study was supported by the Ligue National Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award and the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program. Gynecologic Oncology Group (GOG): This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committtee (CA 101165). Drs. Mark H. Greene and Phuong L. Mai were supported by funding from the Intramural Research Program, NCI, NIH. Hospital Clinico San Carlos (HCSC): HCSC was supported by RETICC 06/0020/0021, FIS research grant 09/00859, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitivity, and the European Regional Development Fund (ERDF)., Helsinki Breast Cancer Study (HEBCS): The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, the Nordic Cancer Union, and the Sigrid Juselius Foundation. Study of Genetic Mutations in Breast and Ovarian Cancer patients in Hong Kong and Asia (HRBCP): HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr. Ellen Li Charitable Foundation, Hong Kong. Molecular Genetic Studies of Breast and Ovarian Cancer in Hungary (HUNBOCS): HUNBOCS was supported by Hungarian Research Grant KTIA-OTKA CK-80745 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/ÖP-9. Institut Català d'Oncologia (ICO): The ICO study was supported by the Asociación Española Contra el Cáncer, Spanish Health Research Foundation, Ramón Areces Foundation, Carlos III Health Institute, Catalan Health Institute, and Autonomous Government of Catalonia and contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI09/02483, PI10/01422, PI10/00748, 2009SGR290, and 2009SGR283. International Hereditary Cancer Centre (IHCC): Supported by the Polish Foundation of Science. Katarzyna Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. Iceland Landspitali–University Hospital (ILUH): The ILUH group was supported by the Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INterdisciplinary HEalth Research Internal Team BReast CAncer susceptibility (INHERIT): INHERIT work was supported by the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, the Canadian Breast Cancer Research Alliance grant 019511 and the Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701. Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics., Istituto Oncologico Veneto (IOVHBOCS): The IOVHBOCS study was supported by Ministero dell'Istruzione, dell'Università e della Ricerca and Ministero della Salute (“Progetto Tumori Femminili” and RFPS 2006-5-341353,ACC2/R6.9”). Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab): kConFab is supported by grants from the National Breast Cancer Foundation and the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. Amanda B. Spurdle is an NHMRC Senior Research Fellow. The Clinical Follow Up Study was funded from 2001–2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333. Mayo Clinic (MAYO): MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. McGill University (MCGILL): The McGill Study was supported by Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation, and Export Trade. Memorial Sloan-Kettering Cancer Center (MSKCC): The MSKCC study was supported by Breast Cancer Research Foundation, Niehaus Clinical Cancer Genetics Initiative, Andrew Sabin Family Foundation, and Lymphoma Foundation. Modifier Study of Quantitative Effects on Disease (MODSQUAD): MODSQUAD was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101). Women's College Research Institute, Toronto (NAROD): NAROD was supported by NIH grant: 1R01 CA149429-01. National Cancer Institute (NCI): Drs. Mark H. Greene and Phuong L. Mai were supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD. National Israeli Cancer Control Center (NICCC): NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. N. N. Petrov Institute of Oncology (NNPIO): The NNPIO study has been supported by the Russian Foundation for Basic Research (grants 11-04-00227, 12-04-00928, and 12-04-01490), the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780), and through a Royal Society International Joint grant (JP090615). The Ohio State University Comprehensive Cancer Center (OSU-CCG): OSUCCG is supported by the Ohio State University Comprehensive Cancer Center., South East Asian Breast Cancer Association Study (SEABASS): SEABASS is supported by the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. Sheba Medical Centre (SMC): The SMC study was partially funded through a grant by the Israel Cancer Association and the funding for the Israeli Inherited Breast Cancer Consortium. Swedish Breast Cancer Study (SWE-BRCA): SWE-BRCA collaborators are supported by the Swedish Cancer Society. The University of Chicago Center for Clinical Cancer Genetics and Global Health (UCHICAGO): UCHICAGO is supported by grants from the US National Cancer Institute (NIH/NCI) and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance, and the Breast Cancer Research Foundation. University of California Los Angeles (UCLA): The UCLA study was supported by the Jonsson Comprehensive Cancer Center Foundation and the Breast Cancer Research Foundation. University of California San Francisco (UCSF): The UCSF study was supported by the UCSF Cancer Risk Program and the Helen Diller Family Comprehensive Cancer Center. United Kingdom Familial Ovarian Cancer Registries (UKFOCR): UKFOCR was supported by a project grant from CRUK to Paul Pharoah. University of Pennsylvania (UPENN): The UPENN study was supported by the National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855), Breast Cancer Research Foundation, Rooney Family Foundation, Susan G. Komen Foundation for the Cure, and the Macdonald Family Foundation. Victorian Familial Cancer Trials Group (VFCTG): The VFCTG study was supported by the Victorian Cancer Agency, Cancer Australia, and National Breast Cancer Foundation. Women's Cancer Research Initiative (WCRI): The WCRI at the Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN).
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- 2013
36. Comparison of 6q25 Breast Cancer Hits from Asian and\ud European Genome Wide Association Studies in the\ud Breast Cancer Association Consortium (BCAC)
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Hein, R., Maranian, M., Hopper, J.L., Kapuscinski, M.K., Southey, M.C., Park, D.J., Schmidt, M.K., Broeks, A., Hogervorst, F.B.L., Bueno-de-Mesquit, H.B., Muir, K.R., Lophatananon, A., Rattanamongkongul, S., Puttawibul, P., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Fletcher, O., Johnson, N., Silva, I.D.S., Peto, J., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Marmee, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Cordina-Duverger, E., Menegaux, F., Truong, T., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Milne, R.L., Arias Perez, J.I., Pilar Zamora, M., Benitez, J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke, C.A., Brenner, H., Mueller, H., Arndt, V., Stegmaier, C., Rahman, N., Seal, S., Turnbull, C., Renwick, A., Meindl, A., Schott, S., Bartram, C.R., Schmutzler, R.K., Brauch, H., Hamann, U., Ko, Y-D., Wang-Gohrke, S., Doerk, T., Schuermann, P., Karstens, J.H., Hillemanns, P., Nevanlinna, H., Heikkinen, T., Aittomaki, K., Blomqvist, C., Bogdanova, N.V., Zalutsky, I.V., Antonenkova, N.N., Bermisheva, M., Prokovieva, D., Farahtdinova, A., Khusnutdinova, E., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J., Chen, X., Beesley, J., Lambrechts, D., Zhao, H., Neven, P., Wildiers, H., Nickels, S., Flesch-Janys, D., Radice, P., Peterlongo, P., Manoukian, S., Barile, M., Couch, F.J., Olson, J.E., Wang, X., Fredericksen, Z., Giles, G.G., Baglietto, L., McLean, C.A., Severi, G., Offit, K., Robson, M., Gaudet, M.M., Vijai, J., Alnaes, G.G., Kristensen, V., Borresen-Dale, A-L., John, E.M., Miron, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Figueroa, J.D., Garcia-Closas, M., Lissowska, J., Sherman, M.E., Hooning, M., Martens, J.W.M., Seynaeve, C., Collee, M., Hall, P., Humpreys, K., Czene, K., Liu, J., Cox, A., Brock, I.W., Cross, S.S., Reed, M.W.R., Ahmed, S., Ghoussaini, M., Pharoah, P.D.P., Kang, D., Yoo, K-Y., Noh, D-Y., Jakubowska, A., Jaworska, K., Durda, K., Zlowocka, E., Sangrajrang, S., Gaborieau, V., Brennan, P., McKay, J., Shen, C-Y., Yu, J-C., Hsu, H-M., Hou, M-F., Orr, N., Schoemaker, M., Ashworth, A., Swerdlow, A., Trentham-Dietz, A., Newcomb, P.A., Titus, L., Egan, K.M., Chenevix-Trench, G., Antoniou, A.C., Humphreys, M.K., Morrison, J., Chang-Claude, J., Easton, D.F., Dunning, A.M., Network, GENICA, Investigators, K, and Group, AOCS
- Abstract
The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single\ud nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports\ud about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP,\ud tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from fortyfour\ud studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European\ud descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were\ud used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER2) tumours. Models including both SNPs\ud were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer\ud risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26–\ud 1.48), p = 7.6610214 in Asians and 1.09 (95% CI 1.07–1.11), p = 6.8610218 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI\ud 1.19–1.41), p = 1.261029 in Asians and 1.12 (95% CI 1.08–1.17), p = 3.861029 in Europeans]. SNP rs2046210 is associated with a\ud significantly greater risk of ER2 than ER+ tumours in Europeans [OR (ER2) = 1.20 (95% CI 1.15–1.25), p = 1.8610217 versus OR\ud (ER+) = 1.07 (95% CI 1.04–1.1), p = 1.361027\ud , pheterogeneity = 5.161026\ud ]. In these Asian studies, by contrast, there is no clear\ud evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other\ud SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in\ud Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER2 tumours.
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- 2012
37. Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
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Couch, F.J., Gaudet, M.M., Antoniou, A.C., Ramus, S.J., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X.Q., Wang, X.S., Kirchhoff, T., McGuffog, L., Barrowdale, D., Lee, A., Healey, S., Sinilnikova, O.M., Andrulis, I.L., Ozcelik, H., Mulligan, A.M., Thomassen, M., Gerdes, A.M., Jensen, U.B., Skytte, A.B., Kruse, T.A., Caligo, M.A., Wachenfeldt, A. von, Barbany-Bustinza, G., Loman, N., Soller, M., Ehrencrona, H., Karlsson, P., Nathanson, K.L., Rebbeck, T.R., Domchek, S.M., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowocka, E., Huzarski, T., Byrski, T., Gronwald, J., Cybulski, C., Gorski, B., Osorio, A., Duran, M., Tejada, M.I., Benitez, J., Hamann, U., Hogervorst, F.B.L., Os, T.A. van, Leeuwen, F.E. van, Meijers-Heijboer, H.E.J., Wijnen, J., Blok, M.J., Kets, M., Hooning, M.J., Oldenburg, R.A., Ausems, M.G.E.M., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Jacobs, C., Eeles, R.A., Adlard, J., Davidson, R., Eccles, D.M., Cole, T., Cook, J., Paterson, J., Brewer, C., Douglas, F., Hodgson, S.V., Morrison, P.J., Walker, L., Porteous, M.E., Kennedy, M.J., Side, L.E., Bove, B., Godwin, A.K., Stoppa-Lyonnet, D., Fassy-Colcombet, M., Castera, L., Cornelis, F., Mazoyer, S., Leone, M., Boutry-Kryza, N., Bressac-de Paillerets, B., Caron, O., Pujol, P., Coupier, I., Delnatte, C., Akloul, L., Lynch, H.T., Snyder, C.L., Buys, S.S., Daly, M.B., Terry, M., Chung, W.K., John, E.M., Miron, A., Southey, M.C., Hopper, J.L., Goldgar, D.E., Singer, C.F., Rappaport, C., Tea, M.K.M., Fink-Retter, A., Hansen, T.V.O., Nielsen, F.C., Arason, A., Vijai, J., Shah, S., Sarrel, K., Robson, M.E., Piedmonte, M., Phillips, K., Basil, J., Rubinstein, W.S., Boggess, J., Wakeley, K., Ewart-Toland, A., Montagna, M., Agata, S., Imyanitov, E.N., Isaacs, C., Janavicius, R., Lazaro, C., Blanco, I., Feliubadalo, L., Brunet, J., Gayther, S.A., Pharoah, P.P.D., Odunsi, K.O., Karlan, B.Y., Walsh, C.S., Olah, E., Teo, S.H., Ganz, P.A., Beattie, M.S., Rensburg, E.J. van, Dorfling, C.M., Diez, O., Kwong, A., Schmutzler, R.K., Wappenschmidt, B., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Heidemann, S., Niederacher, D., Preisler-Adams, S., Gadzicki, D., Varon-Mateeva, R., Deissler, H., Gehrig, A., Sutter, C., Kast, K., Fiebig, B., Heinritz, W., Caldes, T., Hoya, M. de la, Muranen, T.A., Nevanlinna, H., Tischkowitz, M., Spurdle, A.B., Neuhausen, S.L., Ding, Y.C., Lindor, N.M., Fredericksen, Z., Pankratz, V.S., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Barile, M., Bernard, L., Viel, A., Giannini, G., Varesco, L., Radice, P., Greene, M.H., Mai, P.L., Easton, D.F., Chenevix-Trench, G., Offit, K., Simard, J., OCGN, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators, kConFab Investigators, Consortium Investigators Modifiers, European Commission, National Institutes of Health (US), Breast Cancer Research Foundation, Cancer Research UK, Columbia University, Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, Ministerio de Ciencia e Innovación (España), National Institute for Health Research (UK), University of Helsinki, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministero dell'Istruzione, dell'Università e della Ricerca, Ministero della Salute, National Health and Medical Research Council (Australia), Instituto Nacional del Cáncer (España), National Cancer Institute (US), Avon Foundation for Women, VU University medical center, Human genetics, CCA - Oncogenesis, Clinical Genetics, Pediatric Surgery, Neurology, Medical Oncology, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human Genetics, CCA -Cancer Center Amsterdam, and ARD - Amsterdam Reproduction and Development
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Oncology ,endocrine system diseases ,Epidemiology ,Estrogen receptor ,Breast Neoplasms - epidemiology - genetics - metabolism ,DCN PAC - Perception action and control ,Immunoenzyme Techniques ,0302 clinical medicine ,Risk Factors ,Genotype ,skin and connective tissue diseases ,Ovarian Neoplasms ,0303 health sciences ,Ovarian Neoplasms - epidemiology - genetics - metabolism ,BRCA1 Protein ,Middle Aged ,BRCA2 Protein ,Prognosis ,3. Good health ,DNA-Binding Proteins ,Receptors, Estrogen ,Risk factors for breast cancer ,030220 oncology & carcinogenesis ,Mutation (genetic algorithm) ,Female ,Adult ,medicine.medical_specialty ,Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1] ,Breast Neoplasms ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Breast cancer ,SDG 3 - Good Health and Well-being ,Translational research [ONCOL 3] ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetics and epigenetic pathways of disease Translational research [NCMLS 6] ,030304 developmental biology ,Aged ,Chromosomes, Human, Pair 19 - genetics ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,business.industry ,Cancer ,BRCA1 Protein - genetics ,medicine.disease ,United States ,BRCA2 Protein - genetics ,Immunology ,Mutation ,Ovarian cancer ,business ,Chromosomes, Human, Pair 19 ,Genome-Wide Association Study ,Transcription Factors - Abstract
PMCID: PMC3319317.-- et al., [Background]: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). [Methods]: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. [Results]: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10(-3)). [Conclusions]: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. [Impact]: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers., This research was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. This work was also supported by Cancer Research UK (CR-UK) grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). Support was also provided by the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program and by the Canadian Breast Cancer Research Alliance-grant #019511., A.C. Antoniou is a CR-UK Senior Cancer Research Fellow. D.F. Easton is CR-UK Principal Research Fellow. G. Chenevix-Trench6 is a NHMRC Senior Principal Research Fellow. BFBOCC was supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius. BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to E.J. van Rensburg. BCFR was supported by the National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center; U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). CBCS was supported by The Neye Foundation. CNIO was partially supported by Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, the Spanish Ministry of Science and Innovation (FIS PI08 1120), and the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. CONSIT TEAM was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 “Alleanza contro il Cancro” to L. Varesco and P. Radice, and “Progetto Tumori Femminili” to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to P. Radice), Fondazione Italiana per la Ricerca sul Cancro (Special Project “Hereditary tumors” to P. Radice), Associazione Italiana per la Ricerca sul Cancro (4017 to P. Pujol), and by funds from Italian citizens who allocated the 5 × 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”)., The DKFZ study was supported by funds from the DKFZ. EMBRACE was supported by CR-UK Grants C1287/A10118 and C1287/A11990. D.G. Evans and Fiona Lalloo were supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R.A. Eeles, Elizabeth Bancroft, and Lucia D'Mello were supported by CR-UK Grant C5047/A8385. GC-HBOC was supported by a grant of the German Cancer Aid (grant 109076) and by the Centre of Molecular Medicine Cologne (CMMC). The GEMO study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association “Le cancer du sein, parlons-en!” Award. The Georgetown study was supported by the Familial Cancer Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure. GOG was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program—COPTRG) NCI programs. K. Phillips is the Cancer Council Victoria, Colebatch Clinical Research Fellow. HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. HUNBOCS was supported by the Hungarian Research Grant KTIA-OTKA CK-80745. ICO was supported by Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. IHCC was supported by a Polish Foundation of Science award to K. Jaworska, a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. ILUH was supported by the Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund., INHERIT was supported with J. Simard, Chairholder of the Canada Research Chair in Oncogenetics. IOVHBOCS was supported by Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR), and “Ministero della Salute” (“Progetto Tumori Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9”). kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by the NHMRC [145684, 288704, 454508]. A.-B. Skytte is supported by a NHMRC Senior Research Fellowship. A.K. Godwin was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. The McGill study was supported by the Jewish General Hospital Weekend to End Breast Cancer. M. Thomassen holds a Fonds de la Recherche en Santé du Québec clinician-scientist award. The MSKCC study was supported by the Starr Cancer Consortium, the Breast Cancer Research Foundation, the Norman and Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus Clinical Cancer Research Initiative, the Lymphoma Foundation, and the Sabin Family Research Initiative. The NCI study was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. NNPIO was supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) and the Federal Agency for Science and Innovations (contract 16.512.11.2237)., OCGN was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. OSU-CCG was supported by the Ohio State University Comprehensive Cancer Center. PBCS was supported by an Instituto Toscano Tumori grant to M.A. Caligo. SEABASS was supported by CARIF and University Malaya. The UCSF study was supported by the Helen Diller Family Comprehensive Cancer Center at UCSF, the Avon Foundation, and the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS), NIH/NCI P01 CA130818-02A1. UKFOCR was supported by a project grant from CRUK to P.P.D. Pharoah. The UPENN study was supported Komen Foundation for the Cure to S.M. Domchek, the Breast Cancer Research Foundation to K.L. Nathanson, and NIH grants R01-CA083855 and R01-CA102776 to T.R. Rebbeck. WCRI was supported by the American Cancer Society Clinical Research Professorship #SIOP-06-258-06-COUN.
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- 2012
38. Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
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Maxwell, C.A., Benitez, J., Gomez-Baldo, L., Osorio, A., Bonifaci, N., Fernandez-Ramires, R., Costes, S.V., Guino, E., Chen, H., Evans, G.J., Mohan, P., Catala, I., Petit, A., Aguilar, H., Villanueva, A., Aytes, A., Serra-Musach, J., Rennert, G., Lejbkowicz, F., Peterlongo, P., Manoukian, S., Peissel, B., Ripamonti, C.B., Bonanni, B., Viel, A., Allavena, A., Bernard, L., Radice, P., Friedman, E., Kaufman, B., Laitman, Y., Dubrovsky, M., Milgrom, R., Jakubowska, A., Cybulski, C., Gorski, B., Jaworska, K., Durda, K., Sukiennicki, G., Lubinski, J., Shugart, Y.Y., Domchek, S.M., Letrero, R., Weber, B.L., Hogervorst, F.B.L., Rookus, M.A., Collee, J.M., Devilee, P., Ligtenberg, M.J.L., Luijt, R.B. van der, Aalfs, C.M., Waisfisz, Q., Wijnen, J., Roozendaal, C.E.P. van, Easton, D.F., Peock, S., Cook, M., Oliver, C., Frost, D., Harrington, P., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Chu, C., Eccles, D., Douglas, F., Brewer, C., Nevanlinna, H., Heikkinen, T., Couch, F.J., Lindor, N.M., Wang, X., Godwin, A.K., Caligo, M.A., Lombardi, G., Loman, N., Karlsson, P., Ehrencrona, H., Wachenfeldt, A. von, Bjork Barkardottir, R., Hamann, U., Rashid, M.U., Lasa, A., Caldes, T., Andres, R., Schmitt, M., Assmann, V., Stevens, K., Offit, K., Curado, J., Tilgner, H., Guigo, R., Aiza, G., Brunet, J., Castellsague, J., Martrat, G., Urruticoechea, A., Blanco, I., and Tihomirova, L.
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Hereditary cancer and cancer-related syndromes [ONCOL 1] ,Translational research [ONCOL 3] ,skin and connective tissue diseases ,Genetics and epigenetic pathways of disease Translational research [NCMLS 6] - Abstract
Contains fulltext : 98031.pdf (Publisher’s version ) (Open Access) Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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- 2011
39. Effect-Directed Profiling of Strawberry Varieties and Breeding Materials via Planar Chromatography and Chemometrics
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Petar Ristivojević, Nevena Lekić, Ilija Cvijetić, Đurđa Krstić, Filip Andrić, Dušanka Milojković-Opsenica, and Gertrud E. Morlock
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strawberry genotypes ,HPTLC fingerprint ,effect-direct analysis ,principal component analysis ,antioxidative activity ,density functional theory calculation ,Organic chemistry ,QD241-441 - Abstract
Strawberries are an important fruit in the European diet because of their unique taste and high content of essential nutrients and bioactive compounds. The anthocyanins are known to be colorful phenolics in strawberries. In 17 samples of six strawberry cultivars produced in Serbia, i.e., the common varieties Alba, Asia, and Clery as well as promising breeding materials (11.29.11, 11.34.6, and 11.39.3), the anthocyanin profile as well as antimicrobial and antioxidative activity profiles were determined. All investigated extracts showed antioxidative and antibacterial activities against Gram-negative Aliivibrio fischeri. The responses were quite similar in number and intensity. The HPTLC-DPPH• scavenging assay and HPTLC-Aliivibrio fischeri bioassay coupled with high-resolution mass spectrometry identified pelargonidin-3-O-glucoside (Pg-3-glc) as the main anthocyanin and prominent antioxidative and antimicrobial compound in strawberries. The density functional theory calculations at the M06-2X/6-31+G(d,p) level showed that Pg-3-glc quenches free radicals via sequential proton loss electron transfer mechanism in water and in pentyl ethanoate, where the 5-OH group is the most reactive site for proton and hydrogen atom transfer. The results were confirmed via spectrophotometry. The highest total phenolic content was found in Clery and 11.39.3, while statistically significant differences between the genotypes regarding the antioxidant activity were not confirmed. Although very similar in the anthocyanin, antioxidative, and antimicrobial profile patterns, the strawberry genotypes were successfully classified using principal component analysis.
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- 2022
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40. Quality Assessment of Apple and Grape Juices from Serbian and German Markets by Planar Chromatography—Chemometrics
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Đurđa Krstić, Petar Ristivojević, Filip Andrić, Dušanka Milojković-Opsenica, and Gertrud E. Morlock
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high-performance thin-layer chromatography ,HPTLC fingerprint ,effect-directed analysis ,authenticity ,adulteration ,falsification ,Organic chemistry ,QD241-441 - Abstract
The high consumption of plant-based foods on a global scale has increased the number of adulterations in the food industry. Along with this, analytical approaches to fraud detection need to be further developed. A nontargeted effect-directed profiling by high-performance thin-layer chromatography hyphenated with five effect-directed assays (free radical scavenging assay, Aliivibrio fischeri bioassay, and acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibition assays) and multi-imaging provided additional information on the antioxidative, antimicrobial, and enzyme inhibition activities for 18 apple and 18 grape juices from markets in Serbia and Germany. Bioactive zones of interest were eluted using an elution head-based interface and further characterized by electrospray ionization high-resolution mass spectrometry. The different profiles were evaluated chemometrically, and several compounds, which were characteristic of samples from different markets located in Serbia and Germany, were identified in apple juice (such as chlorogenic acid, phloridzin, epicatechin, and caffeic acid) and grape juice (such as chlorogenic acid, epicatechin, and quercetin). The developed rapid and simple method for the quality assessment of fruit juices coming from different (geographic) markets showed clear quality differences. Thus, it could be used to learn more about quality differences, to detect fraud in fruit juice production, and to verify the authenticity of the origin.
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- 2022
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41. Experimental design of photo-Fenton process decolorization of Reactive Red 120 by using mathematical statistics models
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Gordana Pucar Milidrag, Milena Bečelić Tomin, Sanja Rapajić, Miljana Prica, Đurđa Kerkez, Bozo Dalmacija, and Aleksandra Kulić Mandić
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light fastness ,blue wool scale ,printing ink ,colour change ,printability ,Mechanical drawing. Engineering graphics ,T351-385 - Abstract
A statistical design of experiments was used to evaluate the potential use of clay catalyst (CuOFeB) during photo-Fenton process in which the concentration of hydrogen peroxide (H2O2), catalyst loading and pH values were selected as effective experimental factors in the process of dye decolorization. The photo-Fenton oxidation of Reactive Red 120 (RR120) has been investigated using a concentrating solar parabolic reactor with constant solar radiation of 950 W/m2 during summer period of the year. Under the optimal reaction conditions catalyst showed good catalytic activity in the processes with dye removal over 90%. Also, experiment confirmed that decolorization efficiency depends on the pH and concentration of H2O2 , wherein better results were achieved under lower pH values and higher concentration of H2O2.
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- 2018
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42. Optimization of Cyan flexo dye removal by nano zero-valent iron using response surface methodology
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Vesna Kecić, Đurđa Kerkez, Miljana Prica, Sanja Rapajić, Anita Leovac Maćerak, Milena Bečelić-Tomin, and Dragana Tomašević Pilipović
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cyan flexo dye ,nano zero valent iron ,decolorization ,response surface methodology ,optimization process ,Mechanical drawing. Engineering graphics ,T351-385 - Abstract
Application of nano zero-valent iron (nZVI) as a catalyst in a decolorization process is a simple and sensitive method for Cyan flexo dye removal from the aqueous solution. In this paper, a central composite design (CCD), under the response surface methodology (RSM), was applied in order to optimize experimental conditions of the Cyan removal from aqueous solution. The influence of four independent variables was studied: nZVI dosage (5–45 mg L-1), initial dye concentration (2–14 g L-1), pH (2–10) and removal time (20–100 min), in order to build second order quadratic model and to predict the responses. The highest removal percent of 96.35% was attained, and the optimum parameters are achieved after 1h/24h precipitation: nZVI dosage (5/45 mg L-1), initial dye concentration (2/14 g L-1), removal time (20/100 min) and pH (2/10). The Cyan removal efficiency of 38% and 62% were estimated under optimized experimental conditions.
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- 2017
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43. Healing the heart: a randomized pilot study of a spiritual retreat for depression in acute coronary syndrome patients.
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Warber SL, Ingerman S, Moura VL, Wunder J, Northrop A, Gillespie BW, Durda K, Smith K, Rhodes KS, and Rubenfire M
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- 2011
44. Removal of Diclofenac and Metformin from Water in Laboratory Photo Reactor
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Anita Leovac Maćerak, Đurđa Kerkez, Milena Bečelić-Tomin, Dragana Tomašević Pilipović, Aleksandra Kulić, Jovana Jokić, and Božo Dalmacija
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diclofenac ,metformin ,advanced oxidation processes ,wastewater treatment ,General Works - Abstract
Diclofenac (DCF) and metformin (MET) are pharmaceuticals often detected in influents and effluents of municipal sewage treatment plants and surface waters which may cause adverse effects to human health and the environment. In recent years, advanced oxidation processes (AOPs) have been demonstrated to be effective technology for the removal of many organic pollutants. The objective of this study was to evaluate the removal and toxicity of investigated pharmaceuticals by UV and UV/H2O2 processes. UV irradiation was provided by a Pen Ray lamp emission at 254 nm which was covered with a quartz tube and placed in the middle of the reactor. Experimental conditions of the process were: [DIC, MET] = 10 mg/L, [H2O2] = 2.5 mM, reaction time 3 h. Results obtained by only UV exposition of solution showed that diclofenac and metformin were degradated 30% and 50% during 3 h test. Addition of 2.5 mM H2O2 to photo reactor contributed to 90% and 100% removal of DCF and MET, respectively. Inhibition toxicity test of MET increased in the following range: 13% (C0) < 38% (UV) < 77% (UV/ H2O2), while toxicity measured for DCF solutions followed the range: 33% (UV) < 75% (C0) < 78% (UV/H2O2). The results confirmed that addition of hydrogen-peroxide accelerated the removal of investigated pharmaceuticals, but at the same time, lead to formation of the more toxic intermediates. The possible reason for better removal efficiency of metformin can be related to its simpler aliphatic structure in comparison to more aromatic diclofenac.
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- 2018
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45. Removal of As(III) from Water Using 'Green' Synthetized Zero Valent Iron in the Presence of Competing Phosphate Ions
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Đurđa Kerkez, Anita Leovac Maćerak, Milena Bečelić-Tomin, Dragana Tomašević Pilipović, Jovana Jokić, Nataša Slijepčević, and Božo Dalmacija
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nanoscale zero valent iron (nZVI) ,arsenic ,phosphate ,oak leaves ,mulberry leaves ,General Works - Abstract
Nanoscale zero valent iron (nZVI) has been widely investigated for treatment of environmental contaminants. Various technologies are currently available to remove As(III) and phosphate from aqueous environment, but among them, adsorption is most common because its simplicity, treatment stability and cost effectiveness. This study is focused on the removal efficiency of As(III) in the presence of competing phosphate ions by nZVI synthesized using polyphenols from oak and mulberry leaf extracts producing OAK-nZVI and M-nZVI, respectively. The highest removal efficiency of As(III) was obtained for M-nZVI (up to 91% at all nZVI doses). 87% removal was obtained for OAK-nZVI. The same conclusion could be retrieved in the case of PO43− removal (the highest removal, up to 78% at all nZVI doses for M-nZVI). Concerning OAK-nZVI, removal efficiencies increased with increasing nZVI doses (21–76% for doses 2–16 mL). Adsorption of As(III) in the presence of competing PO43− ions on M-nZVI, decreased from 91% to 79%. On OAK-nZVI material, significant changes could not be observed. One can conclude that the presence of PO43− ions in arsenic aqueous solutions would reduce effectiveness of the M-nZVI for As(III) remediation. This conclusion was supported by the fact that M-nZVI particles had a greater antioxidative capacity in comparison to OAK-nZVI which directly influenced nanoparticles synthesis and stability.
- Published
- 2018
- Full Text
- View/download PDF
46. Polyphenolic Profile of Maize Seedlings Treated with 24-Epibrassinolide
- Author
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Hadi Waisi, Aleksandra Kosović, Đurđa Krstić, Dušanka Milojković-Opsenica, Bogdan Nikolić, Vesna Dragičević, and Jelena Trifković
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Chemistry ,QD1-999 - Abstract
High-performance thin-layer chromatography (HPTLC) combined with image analysis and pattern recognition methods were used for fingerprinting of phenolic compounds present in seedlings of two maize genotypes ZP 434 (new generation hybrid, drought tolerant) and ZP 704 (older generation hybrid, drought sensitive) treated with different concentrations of 24-epibrassinolide. This is the first report of TLC chromatographic profile of phenolics’ mixtures in maize seed extracts influenced by brassinosteroid phytohormones. Nine samples of shoot of seedlings for the whole concentration range of phytohormones (5.2 × 10−7–5.2 × 10−15 M), one sample of root of seedlings treated with 5.2 × 10−15 M 24-epibrassinolide, and the control samples of nontreated seedlings, for both genotypes, were analyzed. Phenolic profiles of root extracts indicate the absence of more polar compounds such as phenolic acids and glycosides present in shoot of seedlings. Also, hormones applied in higher concentrations have an inhibiting effect on the content of phenolics in ZP 434. Application of chemometric methods enables characterization of particular genotype of maize according to its phenolic profile.
- Published
- 2015
- Full Text
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47. Selenium as marker for cancer risk and prevention,Selen jako marker ryzyka chorób nowotworowych oraz jego rola w prewencji tych schorzeń
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Lener, M., Jaworska, K., Muszyńska, M., Sukiennicki, G., Durda, K., Gupta, S., Złowocka-Perłowska, E., Kładny, J., Wiechowska-Kozłowska, A., Grodzki, T., Jaworowska, E., Jan Lubinski, Górecka-Szyld, B., Wilk, G., Sulikowski, M., Huzarski, T., Byrski, T., Cybulski, C., Gronwald, J., Dȩbniak, T., Ashuryk, O., Tołoczko-Grabarek, A., Jakubowska, A., Morawski, A., and Lubiński, J.
48. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
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Rebbeck, TR, Friebel, TM, Mitra, N, Wan, F, Chen, S, Andrulis, IL, Apostolou, P, Arnold, N, Arun, BK, Barrowdale, D, Benitez, J, Berger, R, Berthet, P, Borg, A, Buys, SS, Caldes, T, Carter, J, Chiquette, J, Claes, KBM, Couch, FJ, Cybulski, C, Daly, MB, De La Hoya, M, Diez, O, Domchek, SM, Nathanson, KL, Durda, K, Ellis, S, EMBRACE, Evans, DG, Foretova, L, Friedman, E, Frost, D, Ganz, PA, Garber, J, Glendon, G, Godwin, AK, Greene, MH, Gronwald, J, Hahnen, E, Hallberg, E, Hamann, U, Hansen, TVO, HEBON, Imyanitov, EN, Isaacs, C, Jakubowska, A, Janavicius, R, Jaworska-Bieniek, K, John, EM, Karlan, BY, Kaufman, B, Investigators, K, Kwong, A, Laitman, Y, Lasset, C, Lazaro, C, Lester, J, Loman, N, Lubinski, J, Manoukian, S, Mitchell, G, Montagna, M, Neuhausen, SL, Nevanlinna, H, Niederacher, D, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Park, SK, Piedmonte, M, Radice, P, Rappaport-Fuerhauser, C, Rookus, MA, Seynaeve, C, Simard, J, Singer, CF, Soucy, P, Southey, M, Stoppa-Lyonnet, D, Sukiennicki, G, Szabo, CI, Tancredi, M, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Tihomirova, L, Tischkowitz, M, Toland, AE, Toloczko-Grabarek, A, Tung, N, Van Rensburg, EJ, Villano, D, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Zidan, J, Zorn, KK, McGuffog, L, Easton, D, Chenevix-Trench, G, Antoniou, AC, and Ramus, SJ
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skin and connective tissue diseases ,BRCA1 ,hereditary breast and ovarian cancer ,BRCA2 ,transheterozygosity ,3. Good health - Abstract
Background: Most $\textit{BRCA1}$ or $\textit{BRCA2}$ mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both $\textit{BRCA1}$ and $\textit{BRCA2}$ are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female $\textit{BRCA1/2}$ mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at $\textit{BRCA1}$ (SH1) or $\textit{BRCA2}$ (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; $p$ = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 ($p$ = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 ($p$ = 0.231), but was on average 4.5 years younger in TH than in SH2 ($p$ < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive ($p$ = 0.010) or progesterone receptor (PR) positive ($p$ = 0.013) than in SH1, but less likely to be ER positive ($p$ < 0.001) or PR positive ($p$ = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for $\textit{BRCA1}$ or $\textit{BRCA2}$ in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
49. Microelements as risk factors for cancer of the lung and larynx
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Jaworska-Bieniek Katrzyna, Gupta Satish, Durda Katarzyna, Muszynska Magdalena, Sukiennicki Grzegorz, Jaworowska Elżbieta, Grodzki Tomasz, Sulikowski Mieczysław, Woloszczyk Piotr, Wójcik Janusz, Lubiński Jakub, Cybulski Cezary, Dębniak Tadeusz, Lener Marcin, Narod Steven A, Sun Ping, Lubiński Jan, and Jakubowska Anna
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
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50. Zinc and breast cancer risk
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Kaczmarek Katarzyna, Jakubowska Anna, Sukiennicki Grzegorz, Muszyńska Magdalena, Jaworska-Bieniek Katarzyna, Durda Katarzyna, Huzarski Tomasz, Serrano-Fernandez Pablo, Byrski Tomasz, Gronwald Jacek, Gupta Satish, and Lubiński Jan
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
- Full Text
- View/download PDF
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