Search: WFRF:(Amor Dos Santos S. P.)
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The FANCM:p.Arg658*...
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
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- Figlioli, G (author)
- IFOM FIRC Inst Mol Oncol, Genome Diagnost Program, Milan, Italy,IFOM - The FIRC Institute of Molecular Oncology
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Bogliolo, M (author)
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Catucci, I (author)
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show more...
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Caleca, L (author)
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Lasheras, SV (author)
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Pujol, R (author)
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Kiiski, JI (author)
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Muranen, TA (author)
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Barnes, DR (author)
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Dennis, J (author)
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Michailidou, K (author)
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Bolla, MK (author)
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Leslie, G (author)
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Aalfs, CM (author)
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Adank, MA (author)
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Adlard, J (author)
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Agata, S (author)
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Cadoo, K (author)
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Agnarsson, BA (author)
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Ahearn, T (author)
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Aittomaki, K (author)
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Ambrosone, CB (author)
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Andrews, L (author)
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Anton-Culver, H (author)
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Antonenkova, NN (author)
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Arndt, V (author)
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Arnold, N (author)
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Aronson, KJ (author)
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Arun, BK (author)
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Asseryanis, E (author)
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Auber, B (author)
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Auvinen, P (author)
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Azzollini, J (author)
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Balmana, J (author)
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Barkardottir, RB (author)
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Barrowdale, D (author)
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Barwell, J (author)
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Freeman, LEB (author)
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Beauparlant, CJ (author)
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Beckmann, MW (author)
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Behrens, S (author)
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Benitez, J (author)
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Berger, R (author)
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Bermisheva, M (author)
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Blanco, AM (author)
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Blomqvist, C (author)
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Bogdanova, NV (author)
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Bojesen, A (author)
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Bojesen, SE (author)
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Bonanni, B (author)
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Borg, A (author)
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Brady, AF (author)
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Brauch, H (author)
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- Brenner, Hermann (author)
- German Cancer Research Centre
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Bruning, T (author)
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Burwinkel, B (author)
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Buys, SS (author)
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Caldes, T (author)
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Caliebe, A (author)
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Caligo, MA (author)
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Campa, D (author)
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Campbell, IG (author)
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Canzian, F (author)
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Castelao, JE (author)
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Chang-Claude, J (author)
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Chanock, SJ (author)
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Claes, KBM (author)
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Clarke, CL (author)
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Collavoli, A (author)
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Conner, TA (author)
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Cox, DG (author)
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Cybulski, C (author)
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- Czene, K (author)
- Karolinska Institutet
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Daly, MB (author)
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de la Hoya, M (author)
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Devilee, P (author)
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Diez, O (author)
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Ding, YC (author)
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Dite, GS (author)
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Ditsch, N (author)
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Domchek, SM (author)
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Dorfling, CM (author)
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dos-Santos-Silva, I (author)
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Durda, K (author)
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Dwek, M (author)
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Eccles, DM (author)
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Ekici, AB (author)
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Eliassen, AH (author)
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- Ellberg, Carolina (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Eriksson, M (author)
- Karolinska Institutet
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Evans, DG (author)
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- Fasching, PA (author)
- IFOM - The FIRC Institute of Molecular Oncology
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Figueroa, J (author)
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Flyger, H (author)
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Foulkes, WD (author)
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Friebel, TM (author)
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Friedman, E (author)
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- Gabrielson, M (author)
- Karolinska Institutet
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Gaddam, P (author)
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Gago-Dominguez, M (author)
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Gao, C (author)
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Gapstur, SM (author)
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Garber, J (author)
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Garcia-Closas, M (author)
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Garcia-Saenz, JA (author)
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Gaudet, MM (author)
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Gayther, SA (author)
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Giles, GG (author)
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Glendon, G (author)
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Godwin, AK (author)
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Goldberg, MS (author)
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Goldgar, DE (author)
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Guenel, P (author)
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Gutierrez-Barrera, AM (author)
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Haeberle, L (author)
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Haiman, CA (author)
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- Hakansson, N (author)
- Karolinska Institutet
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- Hall, Per (author)
- Lund University,Lunds universitet,Karolinska Institutet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Hamann, U (author)
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Harrington, PA (author)
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Hein, A (author)
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Heyworth, J (author)
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Hillemanns, P (author)
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Hollestelle, A (author)
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Hopper, JL (author)
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Hosgood, HD (author)
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Howell, A (author)
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Hu, CL (author)
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Hulick, PJ (author)
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Hunter, DJ (author)
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Imyanitov, EN (author)
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Isaacs, C (author)
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Jakimovska, M (author)
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Jakubowska, A (author)
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James, P (author)
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Janavicius, R (author)
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Janni, W (author)
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John, EM (author)
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Jones, ME (author)
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Jung, A (author)
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Kaaks, R (author)
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Karlan, BY (author)
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Khusnutdinova, E (author)
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Kitahara, CM (author)
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Konstantopoulou, I (author)
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Koutros, S (author)
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Kraft, P (author)
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Lambrechts, D (author)
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Lazaro, C (author)
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Le Marchand, L (author)
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Lester, J (author)
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Lesueur, F (author)
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Lilyquist, J (author)
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Loud, JT (author)
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Lu, KRH (author)
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Luben, RN (author)
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Lubinski, J (author)
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Mannermaa, A (author)
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Manoochehri, M (author)
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Manoukian, S (author)
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- Margolin, S (author)
- Karolinska Institutet
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Martens, JWM (author)
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Maurer, T (author)
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Mavroudis, D (author)
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Mebirouk, N (author)
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Meindl, A (author)
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Menon, U (author)
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Miller, A (author)
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Montagna, M (author)
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Nathanson, KL (author)
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Neuhausen, SL (author)
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Newman, WG (author)
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Nguyen-Dumont, T (author)
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Nielsen, FC (author)
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Nielsen, S (author)
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Nikitina-Zake, L (author)
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Offit, K (author)
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Olah, E (author)
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Olopade, OI (author)
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Olshan, AF (author)
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Olson, JE (author)
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- Olsson, Håkan (author)
- Lund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Osorio, A (author)
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Ottini, L (author)
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Peissel, B (author)
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Peixoto, A (author)
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Peto, J (author)
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Plaseska-Karanfilska, D (author)
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Pocza, T (author)
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Presneau, N (author)
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Pujana, MA (author)
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Punie, K (author)
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Rack, B (author)
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- Rantala, J (author)
- Karolinska Institutet
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Rashid, MU (author)
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Rau-Murthy, R (author)
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Rennert, G (author)
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Lejbkowicz, F (author)
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Rhenius, V (author)
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Romero, A (author)
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Rookus, MA (author)
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Ross, EA (author)
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Rossing, M (author)
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Rudaitis, V (author)
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Ruebner, M (author)
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Saloustros, E (author)
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Sanden, K (author)
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Santamarina, M (author)
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Scheuner, MT (author)
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Schmutzler, RK (author)
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Schneider, M (author)
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Scott, C (author)
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Senter, L (author)
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Shah, M (author)
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Sharma, P (author)
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Shu, XO (author)
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Simard, J (author)
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Singer, CF (author)
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Sohn, C (author)
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Soucy, P (author)
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Southey, MC (author)
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Spinelli, JJ (author)
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Steele, L (author)
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Stoppa-Lyonnet, D (author)
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Tapper, WJ (author)
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Teixeira, MR (author)
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Terry, MB (author)
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Thomassen, M (author)
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Thompson, J (author)
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Thull, DL (author)
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Tischkowitz, M (author)
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Tollenaar, RAEM (author)
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Torres, D (author)
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Troester, MA (author)
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Truong, T (author)
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Tung, N (author)
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Untch, M (author)
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Vachon, CM (author)
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van Rensburg, EJ (author)
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van Veen, EM (author)
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Vega, A (author)
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Viel, A (author)
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Wappenschmidt, B (author)
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Weitzel, JN (author)
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Wendt, C (author)
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Wieme, G (author)
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- Wolk, Alicja (author)
- Uppsala universitet,Karolinska Institutet,Ortopedi,Karolinska Inst, Inst Environm Med, Stockholm, Sweden
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Yang, XHR (author)
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Zheng, W (author)
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Ziogas, A (author)
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Zorn, KK (author)
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Dunning, AM (author)
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Lush, M (author)
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Wang, Q (author)
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McGuffog, L (author)
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Parsons, MT (author)
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Pharoah, PDP (author)
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Fostira, F (author)
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Toland, AE (author)
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Andrulis, IL (author)
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Ramus, SJ (author)
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Swerdlow, AJ (author)
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Greene, MH (author)
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Chung, WK (author)
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Milne, RL (author)
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Chenevix-Trench, G (author)
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Dork, T (author)
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Schmidt, MK (author)
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Easton, DF (author)
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Radice, P (author)
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Hahnen, E (author)
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Antoniou, AC (author)
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Couch, FJ (author)
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Nevanlinna, H (author)
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Surralles, J (author)
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Peterlongo, P (author)
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Balleine, R (author)
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Baxter, R (author)
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Braye, S (author)
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Carpenter, J (author)
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Dahlstrom, J (author)
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Forbes, J (author)
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Lee, CS (author)
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Marsh, D (author)
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Morey, A (author)
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Pathmanathan, N (author)
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Scott, R (author)
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Simpson, P (author)
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Spigelman, A (author)
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Wilcken, N (author)
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Yip, D (author)
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Zeps, N (author)
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Belotti, M (author)
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Bertrand, O (author)
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Birot, AM (author)
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Caputo, S (author)
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Dupre, A (author)
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Fourme, E (author)
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Gauthier-Villars, M (author)
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Golmard, L (author)
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Le Mentec, M (author)
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Moncoutier, V (author)
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Boutry-Kryza, N (author)
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Calender, A (author)
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Giraud, S (author)
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Leone, M (author)
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Bressac-de-Paillerets, B (author)
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Caron, O (author)
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Guillaud-Bataille, M (author)
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Bonadona, V (author)
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Noguchi, T (author)
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Popovici, C (author)
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Sobol, H (author)
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Pujol, P (author)
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Guimbaud, R (author)
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Feillel, V (author)
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Leroux, CD (author)
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Lallaoui, H (author)
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Chiesa, J (author)
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Molina-Gomes, D (author)
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Manouvrier-Hanu, S (author)
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Greening, S (author)
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Buckley, M (author)
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Friedlander, M (author)
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Koehler, J (author)
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Meiser, B (author)
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Saleh, M (author)
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Salisbury, E (author)
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Trainer, A (author)
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Tucker, K (author)
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Antill, Y (author)
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Dobrovic, A (author)
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Fellows, A (author)
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Nightingale, S (author)
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Kefford, R (author)
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Rickard, E (author)
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Bastick, P (author)
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Scott, C (author)
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Taylor, J (author)
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Brennan, M (author)
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Brown, M (author)
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French, J (author)
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Edwards, S (author)
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Burgess, M (author)
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Burke, J (author)
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Patterson, B (author)
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Butow, P (author)
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Culling, B (author)
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Caldon, L (author)
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Callen, D (author)
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Chauhan, D (author)
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Eisenbruch, M (author)
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Heiniger, L (author)
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Chauhan, M (author)
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Christian, A (author)
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Dixon, J (author)
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Kidd, A (author)
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Cohen, P (author)
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Colley, A (author)
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Fenton, G (author)
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Crook, A (author)
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Dickson, R (author)
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Field, M (author)
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Cui, J (author)
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Cummings, M (author)
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Dawson, SJ (author)
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DeFazio, A (author)
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Delatycki, M (author)
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Dudding, T (author)
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Edkins, T (author)
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Farshid, G (author)
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Flanagan, J (author)
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Fong, P (author)
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Forrest, L (author)
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Gallego-Ortega, D (author)
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George, P (author)
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Gill, G (author)
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Kollias, J (author)
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Haan, E (author)
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Hart, S (author)
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Jenkins, M (author)
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Hunt, C (author)
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Lakhani, S (author)
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Lipton, L (author)
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Lobb, L (author)
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Mann, G (author)
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McLachlan, SA (author)
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O'Connell, S (author)
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O'Sullivan, S (author)
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Pieper, E (author)
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Robinson, B (author)
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Saunus, J (author)
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Scott, E (author)
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Shelling, A (author)
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Williams, R (author)
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- Young, MA (author)
- Genome One, Darlinghurst, NSW, Australia
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(creator_code:org_t)
- 2019-11-01
- 2019
- English.
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In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
- Related links:
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https://www.nature.c...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://dx.doi.org/10... (free)
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- arginine
- arginine 658
- ATM protein
- BRCA1 protein
- BRCA2 protein
- butadiene diepoxide
- checkpoint kinase 2
- olaparib
- partner and localizer of BRCA2
- unclassified drug
- Article
- ATM protein gene
- BRCA1 protein gene
- BRCA2 protein gene
- cell survival
- checkpoint kinase 2 gene
- chromosomal instability
- chromosome fragility
- controlled study
- FANCM gene
- female
- gene
- gene expression
- gene mutation
- genotype
- human
- informed consent
- major clinical study
- mRNA expression level
- partner and localizer of BRCA2 gene
- phenotype
- priority journal
- risk factor
- sensitivity analysis
- survival rate
- triple negative breast cancer
- Western blotting
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Figlioli, G
-
Bogliolo, M
-
Catucci, I
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Caleca, L
-
Lasheras, SV
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Pujol, R
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show more...
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Kiiski, JI
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Muranen, TA
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Barnes, DR
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Dennis, J
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Michailidou, K
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Bolla, MK
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Leslie, G
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Aalfs, CM
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Adank, MA
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Adlard, J
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Agata, S
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Cadoo, K
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Agnarsson, BA
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Ahearn, T
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Aittomaki, K
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Ambrosone, CB
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Andrews, L
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Anton-Culver, H
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Antonenkova, NN
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Arndt, V
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Arnold, N
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Aronson, KJ
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Arun, BK
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Asseryanis, E
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Auber, B
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Auvinen, P
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Azzollini, J
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Balmana, J
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Barkardottir, RB
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Barrowdale, D
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Barwell, J
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Freeman, LEB
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Beauparlant, CJ
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Beckmann, MW
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Behrens, S
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Benitez, J
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Berger, R
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Bermisheva, M
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Blanco, AM
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Blomqvist, C
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Bogdanova, NV
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Bojesen, A
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Bojesen, SE
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Bonanni, B
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Borg, A
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Brady, AF
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Brauch, H
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Brenner, Hermann
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Bruning, T
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Burwinkel, B
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Buys, SS
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Caldes, T
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Caliebe, A
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Caligo, MA
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