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51. FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor

Author: Peterlongo, P, Catucci, I, Colombo, M, Caleca, L, Mucaki, E, Bogliolo, M, Marin, M, Damiola, F, Bernard, L, Pensotti, V, Volorio, S, Dall'Olio, V, Meindl, A, Bartram, C, Sutter, C, Surowy, H, Sornin, V, Dondon, M, Eon-Marchais, S, Stoppa-Lyonnet, D, Andrieu, N, Sinilnikova, O, Mitchell, G, James, P, Thompson, E, Kconfab, Marchetti, M, Verzeroli, C, Tartari, C, Capone, G, Putignano, A, Genuardi, M, Medici, V, Marchi, I, Federico, M, Tognazzo, S, Matricardi, L, Agata, S, Dolcetti, R, Della Puppa, L, Cini, G, Gismondi, V, Viassolo, V, Perfumo, C, Mencarelli, M, Baldassarri, M, Peissel, B, Roversi, G, Silvestri, V, Rizzolo, P, Spina, F, Vivanet, C, Tibiletti, M, Caligo, M, Gambino, G, Tommasi, S, Pilato, B, Tondini, C, Corna, C, Bonanni, B, Barile, M, Osorio, A, Benitez, J, Balestrino, L, Ottini, L, Manoukian, S, Pierotti, M, Renieri, A, Varesco, L, Couch, F, Wang, X, Devilee, P, Hilbers, F, van Asperen, C, Viel, A, Montagna, M, Cortesi, L, Diez, O, Balmaña, J, Hauke, J, Schmutzler, R, Papi, L, Pujana, M, Lázaro, C, Falanga, A, Offit, K, Vijai, J, Campbell, I, Burwinkel, B, Kvist, A, Ehrencrona, H, Mazoyer, S, Pizzamiglio, S, Verderio, P, Surralles, J, Rogan, P, Radice, P, Dondon, MG, Sinilnikova, OM, James, PA, kConFab, Putignano, AL, Mencarelli, MA, Tibiletti, MG, Caligo, MA, Pierotti, MA, Couch, FJ, Hilbers, FS, van Asperen, CJ, Schmutzler, RK, Pujana, MA, Rogan, PK, Peterlongo, P, Catucci, I, Colombo, M, Caleca, L, Mucaki, E, Bogliolo, M, Marin, M, Damiola, F, Bernard, L, Pensotti, V, Volorio, S, Dall'Olio, V, Meindl, A, Bartram, C, Sutter, C, Surowy, H, Sornin, V, Dondon, M, Eon-Marchais, S, Stoppa-Lyonnet, D, Andrieu, N, Sinilnikova, O, Mitchell, G, James, P, Thompson, E, Kconfab, Marchetti, M, Verzeroli, C, Tartari, C, Capone, G, Putignano, A, Genuardi, M, Medici, V, Marchi, I, Federico, M, Tognazzo, S, Matricardi, L, Agata, S, Dolcetti, R, Della Puppa, L, Cini, G, Gismondi, V, Viassolo, V, Perfumo, C, Mencarelli, M, Baldassarri, M, Peissel, B, Roversi, G, Silvestri, V, Rizzolo, P, Spina, F, Vivanet, C, Tibiletti, M, Caligo, M, Gambino, G, Tommasi, S, Pilato, B, Tondini, C, Corna, C, Bonanni, B, Barile, M, Osorio, A, Benitez, J, Balestrino, L, Ottini, L, Manoukian, S, Pierotti, M, Renieri, A, Varesco, L, Couch, F, Wang, X, Devilee, P, Hilbers, F, van Asperen, C, Viel, A, Montagna, M, Cortesi, L, Diez, O, Balmaña, J, Hauke, J, Schmutzler, R, Papi, L, Pujana, M, Lázaro, C, Falanga, A, Offit, K, Vijai, J, Campbell, I, Burwinkel, B, Kvist, A, Ehrencrona, H, Mazoyer, S, Pizzamiglio, S, Verderio, P, Surralles, J, Rogan, P, Radice, P, Dondon, MG, Sinilnikova, OM, James, PA, kConFab, Putignano, AL, Mencarelli, MA, Tibiletti, MG, Caligo, MA, Pierotti, MA, Couch, FJ, Hilbers, FS, van Asperen, CJ, Schmutzler, RK, Pujana, MA, and Rogan, PK
Abstract: Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p. Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p. Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.
Published: 2015

52. Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy

Author: Silvestri, V, Rizzolo, P, Scarnò, M, Chillemi, G, Navazio, A, Valentini, Vincenzo, Zelli, V, Zanna, I, Saieva, C, Masala, G, Bianchi, S, Manoukian, S, Barile, M, Pensotti, V, Peterlongo, P, Varesco, L, Tommasi, S, Russo, A, Giannini, G, Cortesi, L, Viel, A, Montagna, M, Radice, P, Palli, D, Ottini, L., Valentini, Vincenzo (ORCID:0000-0003-4637-6487), Silvestri, V, Rizzolo, P, Scarnò, M, Chillemi, G, Navazio, A, Valentini, Vincenzo, Zelli, V, Zanna, I, Saieva, C, Masala, G, Bianchi, S, Manoukian, S, Barile, M, Pensotti, V, Peterlongo, P, Varesco, L, Tommasi, S, Russo, A, Giannini, G, Cortesi, L, Viel, A, Montagna, M, Radice, P, Palli, D, Ottini, L., and Valentini, Vincenzo (ORCID:0000-0003-4637-6487)
Abstract: Increasing evidence indicates that common genetic variants may contribute to the heritable risk of breast cancer (BC). In this study, we investigated whether single nucleotide polymorphisms (SNPs), within the 8q24.21 multi-cancer susceptibility region and within BC-associated loci widespread in the genome, may influence the risk of BC in men, and whether they may be associated with specific clinical-pathologic characteristics of male BC (MBC). In the frame of the ongoing Italian Multicenter Study on MBC, we performed a case-control study on 386 MBC cases, including 50 BRCA1/2 mutation carriers, and 1105 healthy male controls, including 197 unaffected BRCA1/2 mutation carriers. All 1491 subjects were genotyped by Sequenom iPLEX technology for a total of 29 susceptibility SNPs. By logistic regression models, we found a significant association with MBC risk for five SNPs: rs1562430 (p=0.002) and rs445114 (p=0.026) both within the 8q24.21 region; rs1011970/9p21.3 (p=0.011), rs614367/11q13.3 (p=0.016) and rs1314913/14q24.1 (p<0.0001). Differences in the distribution of rs614367/11q13.3 genotypes according to oestrogen receptor (ER) status (p=0.006), and of rs1011970/9p21.3 genotypes according to human epidermal growth factor receptor 2 (HER2) status (p=0.002) emerged. Association of rs1011970/9p21.3 risk genotype with HER2+MBC was confirmed by a multivariate analysis. rs1314913/14q24.1 was associated with increased MBC risk in analyses restricted to male BRCA1/2 mutation carriers (p=0.041). In conclusion, we provided the first evidence that the 8q24.21 region is associated with MBC risk. Furthermore, we showed that the SNPs rs1562430/8q24.21 and rs1314913/14q24.1 strongly influence BC risk in men and suggested that the SNP rs1314913/14q24.1 may act as a risk modifier locus in male BRCA1/2 mutation carriers.
Published: 2015

53. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Author: 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
Subjects: 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).
Published: 2013

54. Phenotype-Genotype correlations in an extended family with adenomatous coli and an unusual APC gene mutation

Author: PONZ DE LEON M., VARESCO L, BENATTI P, SASSATELLI R, SCARANO MI, ROSSI GB, DI GREGORIO C, GISMONDI V, PERCESEPE A, RONCUCCI L., IZZO, PAOLA, DE ROSA, MARINA, PONZ DE LEON, M., Varesco, L, Benatti, P, Sassatelli, R, Izzo, Paola, Scarano, Mi, Rossi, Gb, DI GREGORIO, C, Gismondi, V, Percesepe, A, DE ROSA, Marina, and Roncucci, L.
Abstract: ISSN 0012-3706
Published: 2001

55. CDKN2A is the main susceptibility gene in Italian pancreatic cancer families

Author: Ghiorzo, Paola, Fornarini, G, Sciallero, S, Battistuzzi, Linda, Belli, F, Bernard, L, Bonelli, L, Borgonovo, Giacomo, Bruno, William, DE CIAN, Franco, Decensi, A, Filauro, M, Faravelli, F, Gozza, A, Gargiulo, Sara, Mariette, F, Nasti, Sabina, Pastorino, Lorenza, Queirolo, P, Savarino, Vincenzo, Varesco, L, Bianchi, Giovanna, Belli, F., Dulbecco, Pietro, Mastracci, Luca, Grillo, Federica, Papadia, FRANCESCO SAVERIO, Queirolo, P., Parodi, C., and Sacchi, G.
Subjects: Adult, Male, Candidate gene, PALB2, DNA Mutational Analysis, Biology, medicine.disease_cause, Germline mutation, Gene Frequency, CDKN2A, Pancreatic cancer, 80 and over, Genetics, medicine, Humans, Genetic Predisposition to Disease, Aged, Aged, 80 and over, Case-Control Studies, Cyclin-Dependent Kinase Inhibitor p16, Female, Genes, Neoplasm, Genetic Association Studies, Germ-Line Mutation, Italy, Middle Aged, Pancreatic Neoplasms, Genetics (clinical), Allele frequency, Mutation, Cancer, medicine.disease, Genes, Neoplasm
Abstract: Background Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms. Patients and methods A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes. Results The CDKN2A mutation rate in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTCCTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations. Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.
Published: 2012

56. 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

Author: 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
Subjects: 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.
Published: 2012

57. ENIGMA - Evidence-based Network for the Interpretation of Germline Mutant Alleles: An international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes

Author: Spurdle, Ab, Healey, S, Devereau, A, Hogervorst, Fb, Monteiro, An, Nathanson, Kl, Radice, P, Stoppa Lyonnet, D, Tavtigian, S, Wappenschmidt, B, Couch, Fj, Goldgar, De, ENIGMA: Goldgar, D, Couch, F, Fackenthal, Jd, Thomassen, M, Teo, Sh, Hansen, Tv, Borg, Å, Eeles, R, Toland, A, Rogan, P, Guidugli, L, Brody, Lc, Brown, M, Kwong, A, Lei po CW, Nevanlinna, H, Garber, J, Foretova, L, Singer, Cf, Blok, Mj, Osorio, A, Kote Jarai, Z, Baralle, D, Vega, A, Blanco, A, Santamariña, M, Fachal, L, Nederlof, P, Peock, S, Pasini, Barbara, Tommasi, S, Lafferty, A, Ansari, A, Konstantopoulou, I, Pal, T, Simard, J, Bonetti, A, Varesco, L, Peissel, B, Evans, Dg, Foulkes, W, Szabo, C, van Asperen, C, Jonkers, J, Walker, L, Mitchell, G, Gutiérrez Enríquez, S, Diez, O, Millot, G, Fostira, F, Selkirk, C, Antoniou, A, Monteiro, A, Carvalho, M, Rubinstein, Ws, de la Hoya, M, Domchek, S, Caputo, S, Houdayer, C, Blanco, I, Lázaro, C, Whiley, P, Becker, A, Aretini, P, Eccles, D, Caldes, T, Viel, A, Izatt, L, Hogervorst, F, Nathanson, K, Pedersen, Is, Vreeswijk, M, Neuhausen, S, Yannoukakos, K, Tucker, K, Southey, M, Leary, J, Caligo, Ma, Gomez Garcia, E, Brandao, R, Lidereau, R, Montagna, M, Pertesi, M, Cornell, M, Rouleau, E, Sharan, S, Rahman, N, Lalloo, F, Weitzel, J, Campbell, J, Cummings, Machakova, E, Olopade, F, Godwin, A, Ozcelik, H, Seminara, D., Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Genetica & Celbiologie, and RS: GROW - School for Oncology and Reproduction
Subjects: Evidence-based practice, unclassified variant, RNA Splicing, Genes, BRCA2, Genes, BRCA1, consortium, Breast Neoplasms, Biology, Article, Germline mutation, breast cancer, Risk Factors, Genetic variation, Genetics, medicine, Humans, Clinical significance, Genetic Predisposition to Disease, BRCA1/BRCA2, Genetic Testing, Allele, unclassified variants, Gene, Genetics (clinical), Alleles, Germ-Line Mutation, Genetic testing, Ovarian Neoplasms, medicine.diagnostic_test, Mechanism (biology), Genetic Variation, BRCA1, BRCA2, ovarian cancer, Germ Cells, Organization and Administration, Data Interpretation, Statistical, international collaboration, Practice Guidelines as Topic, Female, Algorithms
Abstract: As genetic testing for predisposition to human diseases has become an increasingly common practice in medicine, the need for clear interpretation of the test results is apparent. However, for many disease genes, including the breast cancer susceptibility genes BRCA1 and BRCA2, a significant fraction of tests results in the detection of a genetic variant for which disease association is not known. The finding of an "unclassified" variant (UV)/variant of uncertain significance (VUS) complicates genetic test reporting and counseling. As these variants are individually rare, a large collaboration of researchers and clinicians will facilitate studies to assess their association with cancer predisposition. It was with this in mind that the ENIGMA consortium (www.enigmaconsortium.org) was initiated in 2009. The membership is both international and interdisciplinary, and currently includes more than 100 research scientists and clinicians from 19 countries. Within ENIGMA, there are presently six working groups focused on the following topics: analysis, clinical, database, functional, tumor histopathology, and mRNA splicing. ENIGMA provides a mechanism to pool resources, exchange methods and data, and coordinately develop and apply algorithms for classification of variants in BRCA1 and BRCA2. It is envisaged that the research and clinical application of models developed by ENIGMA will be relevant to the interpretation of sequence variants in other disease genes. Hum Mutat 00:1-6, 2011. © 2011 Wiley Periodicals, Inc.
Published: 2011

58. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Antoniou, A. C., Kartsonaki, C., Sinilnikova, O. M., Soucy, P., Mcguffog, L., Healey, S., Lee, A., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Barile, M., Pensotti, V., Pasini, B., Dolcetti, R., Giannini, Giuseppe, Laura Putignano, A., Varesco, L., Radice, P., Mai, P. L., Greene, M. H., Andrulis, I. L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A. M., Kruse, T. A., Jensen, U. B., Cruger, D. G., Caligo, M. A., Laitman, Y., Milgrom, R., Kaufman, B., Paluch Shimon, S., Friedman, E., Loman, N., Harbst, K., Lindblom, A., Arver, B., Ehrencrona, H., Melin, B., Nathanson, K. L., Domchek, S. M., Rebbeck, T., Jakubowska, A., Lubinski, J., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Gorski, B., Osorio, A., Cajal, T. R., Fostira, F., Andres, R., Benitez, J., Hamann, U., Hogervorst, F. B., Rookus, M. A., Hooning, M. J., Nelen, M. R., Van Der Luijt, R. B., Van Os, T. A. M., Van Asperen, C. J., Devilee, P., Meijers Heijboer, H. E. J., Garcia, E. B. G., Peock, S., Cook, M., Frost, D., Platte, R., Leyland, J., Evans, D. G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Eccles, D., Ong, K. R., Cook, J., Douglas, F., Paterson, J., John Kennedy, M., Miedzybrodzka, Z., Godwin, A., Stoppa Lyonnet, D., Buecher, B., Belotti, M., Tirapo, C., Mazoyer, S., Barjhoux, L., Lasset, C., Leroux, D., Faivre, L., Bronner, M., Prieur, F., Nogues, C., Rouleau, E., Pujol, P., Coupier, I., Frenay, M., Hopper, J. L., Daly, M. B., Terry, M. B., John, E. M., Buys, S. S., Yassin, Y., Miron, A., Goldgar, D., Singer, C. F., Tea, M. K., Pfeiler, G., Catharina Dressler, A., Hansen, T. V. O., Jonson, L., Ejlertsen, B., Barkardottir, R. B., Kirchhoff, T., Offit, K., Piedmonte, M., Rodriguez, G., Small, L., Boggess, J., Blank, S., Basil, J., Azodi, M., Toland, A. E., Montagna, M., Tognazzo, S., Agata, S., Imyanitov, E., Janavicius, R., Lazaro, C., Blanco, I., Pharoah, P. D. P., Sucheston, L., Karlan, B. Y., Walsh, C. S., Olah, E., Bozsik, A., Teo, S. H., Seldon, J. L., Beattie, M. S., Van Rensburg, E. J., Sluiter, M. D., Diez, O., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ruehl, I., Varon Mateeva, R., Kast, K., Deissler, H., Niederacher, D., Arnold, N., Gadzicki, D., Schonbuchner, I., Caldes, T., De La Hoya, M., Nevanlinna, H., Aittomaki, K., Dumont, M., Chiquette, J., Tischkowitz, M., Chen, X. Q., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Fredericksen, Z., Wang, X., Pankratz, V. S., Couch, F., Simard, J., Easton, D. F., Chenevix Trench, G., Karlsson, P., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark Askmalm, M., Liedgren, S., Borg, A., Olsson, H., Kristoffersson, U., Jernstrom, H., Henriksson, K., Von Wachenfeldt, A., Liljegren, A., Barbany Bustinza, G., Rantala, J., Gronberg, H., Stattin, E. L., Emanuelsson, M., Brandell, R. R., Dahl, N., Hogervorst, F. B. L., Verhoef, S., Verheus, M., Veer, L. V., Van Leeuwen, F. E., Collee, M., Van Den Ouweland, A. M. W., Jager, A., Tilanus Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., Aalfs, C. M., Van Os, T. A., Gille, J. J. P., Waisfisz, Q., Gomez Garcia, E. B., Van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., Van Der Hout, A. H., Mourits, M. J., Vasen, H. F., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Mckeown, C., Hoffman, J., Donaldson, A., Downing, S., Taylor, A., Murray, A., Rogers, M. T., Mccann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Taylor, J., Side, L., Male, A., Berlin, C., Eason, J., Collier, R., Claber, O., Jobson, I., Walker, L., Mcleod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Lucassen, A., Crawford, G., Mcbride, D., Smalley, S., University of Groningen, Clinical Genetics, Medical Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] ( CAM ), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Queensland Institute of Medical Research, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Consortium for Genomics Technology (Cogentech), Department of Genetics, Biology and Biochemistry, University of Turin, Cancer Bioimmunotherapy Unit, IRCCS-Centro di Riferimento Oncologico, Department of Experimental Medicine, Università degli Studi di Roma 'La Sapienza' [Rome], Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Ontario Cancer Genetics Network, Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital ( MSH ), Department of Clinical Genetics, Odense University Hospital, Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Department of Oncology, Lund University Hospital, Karolinska University Hospital [Stockholm], Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Department of Radiation Sciences and Oncology, Umeå University, Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine-Abramson Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, International Hereditary Cancer Center, Pomeranian Medical University, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Department of Medical Oncology, Hospital Sant Pau, Medical Oncology Division, Hospital Clínico de Zaragoza, Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum ( DKFZ ), Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Wessex Clinical Genetics Service, Princess Anne Hospital, West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Newcastle Upon Tyne Hospitals NHS Trust, Addenbrookes Hospital, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Service de Génétique Oncologique, INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), génétique, Centre de Recherche en Cancérologie de Lyon ( 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 ), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Service d'onco-hématologie et génétique, CHU Grenoble, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Santé Publique, Hôpital René HUGUENIN (Saint-Cloud)-INSTITUT CURIE, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Institut de recherche en cancérologie de Montpellier ( IRCM - U896 Inserm - UM1 ), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Consultation d'oncogénétique, CRLCC Antoine Lacassagne, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] ( HMS ), Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Division of Special Gynecology, Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Rigshospitalet [Copenhagen], Department of Pathology, Landspitali-University Hospital, Department of Environmental Medicine, New York University School of Medicine-NYU Cancer Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, State Research Institute Innovative Medicine Center, Molecular Diagnostic Unit, IDIBELL-Catalan Institute of Oncology, Genetic Counselling Unit, Department of Molecular Genetics, National Institute of Oncology, Cancer Research Initiatives Foundation, Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre, Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximillians University, Charite berlin, University Hospital Carl Gustav Carus, University Hospital Ulm, University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] ( MHH ), University of Würzburg, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Genetics, Portuguese Oncology Institute, Department of Medical Genetics, Mayo Clinic, Department of Laboratory Medicine and Pathology, Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Firenze = University of Florence (UniFI), National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Clinical Genetics [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Tel Aviv University (TAU), Uppsala University, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Abramson Cancer Center-Perelman School of Medicine, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Pomeranian Medical University [Szczecin] (PUM), Hospital de la Santa Creu i Sant Pau, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universiteit Leiden-Universiteit Leiden, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Newcastle Upon Tyne Hospitals NHS Foundation Trust, University of Kansas Medical Center [Kansas City, KS, USA], Institut Curie [Paris], 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), 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), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), 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 Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Harvard Medical School [Boston] (HMS), Medizinische Universität Wien = Medical University of Vienna, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry [Rigshospitalet], Copenhagen University Hospital, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Roswell Park Cancer Institute [Buffalo] (RPCI), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), Hannover Medical School [Hannover] (MHH), Julius-Maximilians-Universität Würzburg (JMU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital René HUGUENIN (Saint-Cloud)-Institut Curie [Paris], CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Universität Leipzig [Leipzig], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), University of Florence (UNIFI), Mount Sinai Hospital (MSH), Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), 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), Institut Curie-Hôpital René HUGUENIN (Saint-Cloud), Technical University of Munich (TUM), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Human genetics, CCA - Oncogenesis, Human Genetics, Klinische Genetica, and RS: GROW - School for Oncology and Reproduction
Subjects: MESH : BRCA2 Protein, MESH : Aged, Estrogen receptor, Genome-wide association study, MESH : Breast Neoplasms, VARIANTS, MESH : Chromosomes, Human, Pair 1, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Chromosomes, Human, Pair 6, MESH: BRCA2 Protein, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Genotype, CONFER SUSCEPTIBILITY, Chromosomes, Human, MESH : Female, skin and connective tissue diseases, Genetics (clinical), POPULATION, MESH: Heterozygote, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Adult, Middle Aged, MESH : Risk Factors, 3. Good health, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 6, Female, MESH : Mutation, Adult, MESH : Heterozygote, Heterozygote, MESH: Mutation, MESH: Chromosomes, Human, Pair 6, MESH: Chromosomes, Human, Pair 1, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Breast Neoplasms, Biology, MESH: Chromosomes, Human, Polymorphism, Single Nucleotide, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Genetics, medicine, LOCUS, SNP, Humans, MESH : Middle Aged, MESH : BRCA1 Protein, Genetic Predisposition to Disease, Allele, GENOME-WIDE ASSOCIATION, education, Molecular Biology, Alleles, MESH: BRCA1 Protein, 030304 developmental biology, Aged, BRCA2 Protein, MESH: Humans, 2Q35, MESH: Alleles, MESH : Humans, MESH: Adult, medicine.disease, MESH : Chromosomes, Human, ESTROGEN-RECEPTOR, Mutation, Cancer research, MESH : Genetic Predisposition to Disease, GENETIC MODIFIERS, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms
Abstract: Item does not contain fulltext Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
Published: 2011

59. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

Author: Osorio, A., Milne, R.L., Kuchenbaecker, K., Vaclova, T., Pita, G., Alonso, R., Peterlongo, P., Blanco, I., Hoya, M. de la, Duran, M., Diez, O., Ramon, Y.C.T., Konstantopoulou, I., Martinez-Bouzas, C., Conejero, R. Andres, Soucy, P., McGuffog, L., Barrowdale, D., Lee, A., Swe, B., Arver, B., Rantala, J., Loman, N., Ehrencrona, H., Olopade, O.I., Beattie, M.S., Domchek, S.M., Nathanson, K., Rebbeck, T.R., Arun, B.K., Karlan, B.Y., Walsh, C., Lester, J., John, E.M., Whittemore, A.S., Daly, M.B., Southey, M., Hopper, J., Terry, M.B., Buys, S.S., Janavicius, R., Dorfling, C.M., Rensburg, E.J. van, Steele, L., Neuhausen, S.L., Ding, Y.C., Hansen, T.V., Jonson, L., Ejlertsen, B., Gerdes, A.M., Infante, M., Herraez, B., Moreno, L.T., Weitzel, J.N., Herzog, J., Weeman, K., Manoukian, S., Peissel, B., Zaffaroni, D., Scuvera, G., Bonanni, B., Mariette, F., Volorio, S., Viel, A., Varesco, L., Papi, L., Ottini, L., Tibiletti, M.G., Radice, P., Yannoukakos, D., Garber, J., Ellis, S., Frost, D., Platte, R., Fineberg, E., Evans, G., Lalloo, F., Izatt, L., Eeles, R., Adlard, J., Davidson, R., Cole, T., Eccles, D., Cook, J., Hodgson, S., Brewer, C., Tischkowitz, M., Douglas, F., Porteous, M., Side, L., Walker, L., Morrison, P., Donaldson, A., Kennedy, J., Foo, C., Godwin, A.K., Schmutzler, R.K., Wappenschmidt, B., Rhiem, K., Engel, C., Hoogerbrugge-van der Linden, N., et al., Osorio, A., Milne, R.L., Kuchenbaecker, K., Vaclova, T., Pita, G., Alonso, R., Peterlongo, P., Blanco, I., Hoya, M. de la, Duran, M., Diez, O., Ramon, Y.C.T., Konstantopoulou, I., Martinez-Bouzas, C., Conejero, R. Andres, Soucy, P., McGuffog, L., Barrowdale, D., Lee, A., Swe, B., Arver, B., Rantala, J., Loman, N., Ehrencrona, H., Olopade, O.I., Beattie, M.S., Domchek, S.M., Nathanson, K., Rebbeck, T.R., Arun, B.K., Karlan, B.Y., Walsh, C., Lester, J., John, E.M., Whittemore, A.S., Daly, M.B., Southey, M., Hopper, J., Terry, M.B., Buys, S.S., Janavicius, R., Dorfling, C.M., Rensburg, E.J. van, Steele, L., Neuhausen, S.L., Ding, Y.C., Hansen, T.V., Jonson, L., Ejlertsen, B., Gerdes, A.M., Infante, M., Herraez, B., Moreno, L.T., Weitzel, J.N., Herzog, J., Weeman, K., Manoukian, S., Peissel, B., Zaffaroni, D., Scuvera, G., Bonanni, B., Mariette, F., Volorio, S., Viel, A., Varesco, L., Papi, L., Ottini, L., Tibiletti, M.G., Radice, P., Yannoukakos, D., Garber, J., Ellis, S., Frost, D., Platte, R., Fineberg, E., Evans, G., Lalloo, F., Izatt, L., Eeles, R., Adlard, J., Davidson, R., Cole, T., Eccles, D., Cook, J., Hodgson, S., Brewer, C., Tischkowitz, M., Douglas, F., Porteous, M., Side, L., Walker, L., Morrison, P., Donaldson, A., Kennedy, J., Foo, C., Godwin, A.K., Schmutzler, R.K., Wappenschmidt, B., Rhiem, K., Engel, C., Hoogerbrugge-van der Linden, N., and et al.
Abstract: Contains fulltext : 137733.pdf (publisher's version ) (Open Access), Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 x 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 x 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
Published: 2014

60. DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Osorio, A. (Ana), Milne, R.L. (Roger), Kuchenbaecker, K.B. (Karoline), Vaclová, T. (Tereza), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Peterlongo, P. (Paolo), Blanco, I. (Ignacio), Hoya, M. (Miguel) de La, Durán, M. (Mercedes), Díez, O. (Orland), Ramon Y Cajal, T., Konstantopoulou, I. (I.), Martínez-Bouzas, C. (Cristina), Andrés Conejero, R. (Raquel), Soucy, P. (Penny), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Arver, B. (Brita Wasteson), Rantala, J. (Johanna), Loman, N. (Niklas), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Beattie, M.S. (Mary), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Arun, B.K. (Banu), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), John, E.M. (Esther), Whittemore, A.S. (Alice), Daly, M.B. (Mary), Southey, M.C. (Melissa), Hopper, J.L. (John), Terry, M.-B. (Mary-Beth), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Infante, J. (Jon), Herráez, B. (Belén), Moreno, L.T. (Leticia Thais), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Weeman, K. (Kisa), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariette, F. (F.), Volorio, S. (Sara), Viel, A. (Alessandra), Varesco, L. (Liliana), Papi, L. (Laura), Ottini, L. (Laura), Tibiletti, M.G. (Maria Grazia), Radice, P. (Paolo), Yannoukakos, D. (Drakoulis), Garber, J., Ellis, S.D. (Steve), Frost, D. (Debra), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Cole, T.J. (Trevor), Eccles, D. (Diana), Cook, J. (Jackie), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Tischkowitz, M. (Marc), Douglas, F. (Fiona), Porteous, M.E. (Mary), Side, L. (Lucy), Walker, L.J. (Lisa), Morrison, P.J. (Patrick), Donaldson, A. (Alan), Kennedy, J. (John), Foo, C. (Claire), Godwin, A.K. (Andrew), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Stoppa-Lyonnet, D. (Dominique), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Poppe, B. (Bruce), Claes, K. (Kathleen), Piedmonte, M. (Marion), Tucker, K. (Kathryn), Backes, F.J. (Floor), Rodríguez, P.M., Brewster, W. (Wendy), Wakeley, K. (Katie), Rutherford, T. (Thomas), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Rookus, M.A. (Matti), Os, T.A.M. (Theo) van, Kolk, L.E. (Lizet) van der, Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Asperen, C.J. (Christi) van, Gómez García, E.B. (Encarna), Hoogerbrugge, N. (Nicoline), Collée, J.M. (Margriet), Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Devilee, P. (Peter), Olah, E. (Edith), Lázaro, C. (Conxi), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Johannson, O.T. (Oskar), Maugard, C., Montagna, M. (Marco), Tognazzo, S. (Silvia), Teixeira, P.J., Healey, S. (Sue), Olswold, C. (Curtis), Guidugli, L. (Lucia), Lindor, N.M. (Noralane), Slager, S. (Susan), Szabo, C. (Csilla), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Zhang, L. (Lingling), Rau-Murthy, R. (Rohini), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Berger, A. (Annemarie), Phelan, C. (Catherine), Greene, M.H. (Mark), Mai, P.L. (Phuong), Lejbkowicz, F. (Flavio), Andrulis, I.L. (Irene), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, S.E. (Stig), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Thomassen, M. (Mads), Kruse, T.A. (Torben), Jensen, U.B., Friedman, E. (Eitan), Laitman, Y. (Yael), Shimon, S.P. (Shani Paluch), Simard, J. (Jacques), Easton, D.F. (Douglas), Offit, K. (Kenneth), Couch, F.J. (Fergus), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Benítez, J. (Javier), Osorio, A. (Ana), Milne, R.L. (Roger), Kuchenbaecker, K.B. (Karoline), Vaclová, T. (Tereza), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Peterlongo, P. (Paolo), Blanco, I. (Ignacio), Hoya, M. (Miguel) de La, Durán, M. (Mercedes), Díez, O. (Orland), Ramon Y Cajal, T., Konstantopoulou, I. (I.), Martínez-Bouzas, C. (Cristina), Andrés Conejero, R. (Raquel), Soucy, P. (Penny), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Arver, B. (Brita Wasteson), Rantala, J. (Johanna), Loman, N. (Niklas), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Beattie, M.S. (Mary), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Arun, B.K. (Banu), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), John, E.M. (Esther), Whittemore, A.S. (Alice), Daly, M.B. (Mary), Southey, M.C. (Melissa), Hopper, J.L. (John), Terry, M.-B. (Mary-Beth), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Infante, J. (Jon), Herráez, B. (Belén), Moreno, L.T. (Leticia Thais), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Weeman, K. (Kisa), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariette, F. (F.), Volorio, S. (Sara), Viel, A. (Alessandra), Varesco, L. (Liliana), Papi, L. (Laura), Ottini, L. (Laura), Tibiletti, M.G. (Maria Grazia), Radice, P. (Paolo), Yannoukakos, D. (Drakoulis), Garber, J., Ellis, S.D. (Steve), Frost, D. (Debra), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Cole, T.J. (Trevor), Eccles, D. (Diana), Cook, J. (Jackie), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Tischkowitz, M. (Marc), Douglas, F. (Fiona), Porteous, M.E. (Mary), Side, L. (Lucy), Walker, L.J. (Lisa), Morrison, P.J. (Patrick), Donaldson, A. (Alan), Kennedy, J. (John), Foo, C. (Claire), Godwin, A.K. (Andrew), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Stoppa-Lyonnet, D. (Dominique), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Poppe, B. (Bruce), Claes, K. (Kathleen), Piedmonte, M. (Marion), Tucker, K. (Kathryn), Backes, F.J. (Floor), Rodríguez, P.M., Brewster, W. (Wendy), Wakeley, K. (Katie), Rutherford, T. (Thomas), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Rookus, M.A. (Matti), Os, T.A.M. (Theo) van, Kolk, L.E. (Lizet) van der, Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Asperen, C.J. (Christi) van, Gómez García, E.B. (Encarna), Hoogerbrugge, N. (Nicoline), Collée, J.M. (Margriet), Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Devilee, P. (Peter), Olah, E. (Edith), Lázaro, C. (Conxi), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Johannson, O.T. (Oskar), Maugard, C., Montagna, M. (Marco), Tognazzo, S. (Silvia), Teixeira, P.J., Healey, S. (Sue), Olswold, C. (Curtis), Guidugli, L. (Lucia), Lindor, N.M. (Noralane), Slager, S. (Susan), Szabo, C. (Csilla), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Zhang, L. (Lingling), Rau-Murthy, R. (Rohini), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Berger, A. (Annemarie), Phelan, C. (Catherine), Greene, M.H. (Mark), Mai, P.L. (Phuong), Lejbkowicz, F. (Flavio), Andrulis, I.L. (Irene), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, S.E. (Stig), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Thomassen, M. (Mads), Kruse, T.A. (Torben), Jensen, U.B., Friedman, E. (Eitan), Laitman, Y. (Yael), Shimon, S.P. (Shani Paluch), Simard, J. (Jacques), Easton, D.F. (Douglas), Offit, K. (Kenneth), Couch, F.J. (Fergus), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), and Benítez, J. (Javier)
Abstract: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.1
Published: 2014
Full Text: View/download PDF

61. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author: Spurdle, A.B. (Amanda), Couch, F.J. (Fergus), Parsons, M. (Marilyn), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Healey, S. (Sue), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Hahnen, E. (Eric), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Ellis, S.D. (Steve), Frost, D. (Debra), Platte, R. (Radka), Perkins, J. (Jo), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, L., Davidson, R. (Rosemarie), Cole, T.J. (Trevor), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Bonnani, B. (Bernardo), Mariette, F. (F.), Fortuzzi, S. (S.), Viel, A. (Alessandra), Pasini, B. (Barbara), Papi, L. (Laura), Varesco, L. (Liliana), Balleine, R. (Rosemary), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Offitt, K. (Kenneth), Jakubowska, A. (Anna), Lindor, N.M. (Noralane), Thomassen, M. (Mads), Jensen, U.B., Rantala, J. (Johanna), Borg, Å. (Åke), Andrulis, I.L. (Irene), Miron, A. (Alexander), Hansen, T.V.O. (Thomas), Caldes, T. (Trinidad), Neuhausen, S.L. (Susan), Toland, A.E. (Amanda), Nevanlinna, H. (Heli), Montagna, M. (Marco), Garber, J. (Judy), Godwin, A.K. (Andrew), Osorio, A. (Ana), Factor, R.E. (Rachel E.), Terry, M.B. (Mary B.), Rebbeck, R. (Timothy), Karlan, B.Y. (Beth), Southey, M.C. (Melissa), Rashid, M.U. (Muhammad), Tung, N. (Nadine), Pharoah, P.D.P. (Paul), Blows, F. (Fiona), Dunning, A.M. (Alison), Provenzano, E. (Elena), Hall, P. (Per), Czene, K. (Kamila), Schmidt, M.K. (Marjanka), Broeks, A. (Annegien), Cornelissen, S. (Sten), Verhoef, S., Fasching, P.A. (Peter), Beckmann, M.W. (Matthias), Ekici, A.B. (Arif), Slamon, D.J. (Dennis), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Nielsen, S.F. (Sune), Flyger, H. (Henrik), Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Rudolph, A. (Anja), Seibold, P. (Petra), Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Heikkilä, P. (Päivi), Blomqvist, C. (Carl), Figueroa, J.D. (Jonine), Chanock, S.J. (Stephen), Brinton, L.A. (Louise), Lissowska, J. (Jolanta), Olson, J.E. (Janet), Pankratz, V.S. (Shane), John, E.M. (Esther), Whittemore, A.S. (Alice), West, D. van, Hamann, U. (Ute), Torres, D. (Diana), Ulmer, H.U. (Hans), Rud̈iger, T. (Thomas), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, Eccles, D. (Diana), Tapper, W. (William), Durcan, L. (Lorraine), Jones, L. (Louise), Peto, J. (Julian), Santos Silva, I. (Isabel) dos, Fletcher, O. (Olivia), Johnson, N. (Nichola), Dwek, M. (Miriam), Swann, R. (Ruth), Bane, A.L. (Anita L.), Glendon, G. (Gord), Mulligan, A.M. (Anna Marie), Giles, G.G. (Graham), Milne, R.L. (Roger), Baglietto, L. (Laura), McLean, C.A. (Catriona Ann), Carpenter, J. (Jane), Clarke, C. (Christine), Scott, R.J. (Rodney), Brauch, H. (Hiltrud), Brüning, T. (Thomas), Ko, Y-D. (Yon-Dschun), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Lubinski, J. (Jan), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Gronwald, J. (Jacek), Dörk, T. (Thilo), Bogdanova, N.V. (Natalia), Park-Simon, T.-W., Hillemanns, P. (Peter), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Schumacher, F.R. (Fredrick), Le Marchand, L. (Loic), Burwinkel, B. (Barbara), Marme, F. (Federick), Surovy, H. (Harald), Yang, R. (Rongxi), Anton-Culver, H. (Hoda), Ziogas, A. (Argyrios), Hooning, M.J. (Maartje), Collée, J.M. (Margriet), Martens, J.W.M. (John), Tilanus-Linthorst, M.M.A. (Madeleine), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Grip, M. (Mervi), Lindblom, A. (Annika), Margolin, S. (Sara), Joseph, V. (Vijai), Robson, M. (Mark), Rau-Murthy, R. (Rohini), González-Neira, A. (Anna), Arias Pérez, J.I. (José Ignacio), Zamora, P. (Pilar), Benítez, J. (Javier), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Peterlongo, P. (Paolo), Zaffaroni, D. (D.), Barile, M. (Monica), Capra, F. (Fabio), Radice, P. (Paolo), Teo, S.-H. (Soo-Hwang), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Chenevix-Trench, G. (Georgia), Goldgar, D. (David), Spurdle, A.B. (Amanda), Couch, F.J. (Fergus), Parsons, M. (Marilyn), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Healey, S. (Sue), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Hahnen, E. (Eric), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Ellis, S.D. (Steve), Frost, D. (Debra), Platte, R. (Radka), Perkins, J. (Jo), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, L., Davidson, R. (Rosemarie), Cole, T.J. (Trevor), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Bonnani, B. (Bernardo), Mariette, F. (F.), Fortuzzi, S. (S.), Viel, A. (Alessandra), Pasini, B. (Barbara), Papi, L. (Laura), Varesco, L. (Liliana), Balleine, R. (Rosemary), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Offitt, K. (Kenneth), Jakubowska, A. (Anna), Lindor, N.M. (Noralane), Thomassen, M. (Mads), Jensen, U.B., Rantala, J. (Johanna), Borg, Å. (Åke), Andrulis, I.L. (Irene), Miron, A. (Alexander), Hansen, T.V.O. (Thomas), Caldes, T. (Trinidad), Neuhausen, S.L. (Susan), Toland, A.E. (Amanda), Nevanlinna, H. (Heli), Montagna, M. (Marco), Garber, J. (Judy), Godwin, A.K. (Andrew), Osorio, A. (Ana), Factor, R.E. (Rachel E.), Terry, M.B. (Mary B.), Rebbeck, R. (Timothy), Karlan, B.Y. (Beth), Southey, M.C. (Melissa), Rashid, M.U. (Muhammad), Tung, N. (Nadine), Pharoah, P.D.P. (Paul), Blows, F. (Fiona), Dunning, A.M. (Alison), Provenzano, E. (Elena), Hall, P. (Per), Czene, K. (Kamila), Schmidt, M.K. (Marjanka), Broeks, A. (Annegien), Cornelissen, S. (Sten), Verhoef, S., Fasching, P.A. (Peter), Beckmann, M.W. (Matthias), Ekici, A.B. (Arif), Slamon, D.J. (Dennis), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Nielsen, S.F. (Sune), Flyger, H. (Henrik), Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Rudolph, A. (Anja), Seibold, P. (Petra), Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Heikkilä, P. (Päivi), Blomqvist, C. (Carl), Figueroa, J.D. (Jonine), Chanock, S.J. (Stephen), Brinton, L.A. (Louise), Lissowska, J. (Jolanta), Olson, J.E. (Janet), Pankratz, V.S. (Shane), John, E.M. (Esther), Whittemore, A.S. (Alice), West, D. van, Hamann, U. (Ute), Torres, D. (Diana), Ulmer, H.U. (Hans), Rud̈iger, T. (Thomas), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, Eccles, D. (Diana), Tapper, W. (William), Durcan, L. (Lorraine), Jones, L. (Louise), Peto, J. (Julian), Santos Silva, I. (Isabel) dos, Fletcher, O. (Olivia), Johnson, N. (Nichola), Dwek, M. (Miriam), Swann, R. (Ruth), Bane, A.L. (Anita L.), Glendon, G. (Gord), Mulligan, A.M. (Anna Marie), Giles, G.G. (Graham), Milne, R.L. (Roger), Baglietto, L. (Laura), McLean, C.A. (Catriona Ann), Carpenter, J. (Jane), Clarke, C. (Christine), Scott, R.J. (Rodney), Brauch, H. (Hiltrud), Brüning, T. (Thomas), Ko, Y-D. (Yon-Dschun), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Lubinski, J. (Jan), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Gronwald, J. (Jacek), Dörk, T. (Thilo), Bogdanova, N.V. (Natalia), Park-Simon, T.-W., Hillemanns, P. (Peter), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Schumacher, F.R. (Fredrick), Le Marchand, L. (Loic), Burwinkel, B. (Barbara), Marme, F. (Federick), Surovy, H. (Harald), Yang, R. (Rongxi), Anton-Culver, H. (Hoda), Ziogas, A. (Argyrios), Hooning, M.J. (Maartje), Collée, J.M. (Margriet), Martens, J.W.M. (John), Tilanus-Linthorst, M.M.A. (Madeleine), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Grip, M. (Mervi), Lindblom, A. (Annika), Margolin, S. (Sara), Joseph, V. (Vijai), Robson, M. (Mark), Rau-Murthy, R. (Rohini), González-Neira, A. (Anna), Arias Pérez, J.I. (José Ignacio), Zamora, P. (Pilar), Benítez, J. (Javier), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Peterlongo, P. (Paolo), Zaffaroni, D. (D.), Barile, M. (Monica), Capra, F. (Fabio), Radice, P. (Paolo), Teo, S.-H. (Soo-Hwang), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Chenevix-Trench, G. (Georgia), and Goldgar, D. (David)
Abstract: Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the l
Published: 2014
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62. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, K.B. (Karoline), Neuhausen, S.L. (Susan), Robson, M. (Mark), Barrowdale, D. (Daniel), McGuffog, L. (Lesley), Mulligan, A.M. (Anna Marie), Andrulis, I.L. (Irene), Spurdle, A.B. (Amanda), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Engel, C. (Christoph), Wapenschmidt, B. (Barbara), Nevanlinna, H. (Heli), Thomassen, M. (Mads), Southey, M.C. (Melissa), Radice, P. (Paolo), Ramus, S.J. (Susan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Lee, A. (Andrew), Healey, S. (Sue), Nussbaum, R. (Robert), Rebbeck, R. (Timothy), Arun, B.K. (Banu), James, M. (Margaret), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Cass, I. (Ilana), Terry, M.B. (Mary Beth), Daly, M.J. (Mark), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Overeem Hansen, T. (Thomas) van, Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Nielsen, F. (Finn), Dennis, J. (Joe), Cunningham, J.M. (Julie), Hart, S. (Stewart), Slager, S. (Susan), Osorio, A. (Ana), Benítez, J. (Javier), Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Tafur, I. (Isaac), Hander, M. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Roversi, G. (Gaia), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariani, P. (Paolo), Volorio, S. (Sara), Dolcetti, R. (Riccardo), Varesco, L. (Liliana), Papi, L. (Laura), Tibiletti, M.G. (Maria Grazia), Giannini, G. (Giuseppe), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Ong, K., Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Godwin, A.K. (Andrew), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Steinemann, D. (Doris), Bogdanova-Markov, N. (Nadja), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Gehrig, P.A. (Paola A.), Markiefka, B. (Birgid), Buecher, B. (Bruno), Lefol, C. (Cédrick), Stoppa-Lyonnet, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Barjhoux, L. (Laure), Faivre, L. (Laurence), Longy, M. (Michel), Sevenet, N. (Nicolas), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Caux-Moncoutier, V. (Virginie), Isaacs, C. (Claudine), Van Maerken, T. (Tom), Claes, K.B.M. (Kathleen B.M.), Piedmonte, M. (Marion), Andrews, L. (Lesley), Hays, J. (John), Rodriguez, G.C. (Gustavo), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Khan, S. (Sofia), Hogervorst, F.B.L. (Frans), Aalfs, C.M. (Cora), Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Wijnen, J.T. (Juul), Roozendaal, K.E. (Kees) van, Mensenkamp, A.R. (Arjen), Ouweland, A.M.W. (Ans) van den, Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Lubinski, J. (Jan), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Arason, A. (Adalgeir), Maugard, C., Soucy, P. (Penny), Montagna, M. (Marco), Agata, S. (Simona), Teixeira, P.J., Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Hallberg, B. (Boubou), Wang, X. (Xianshu), Szabo, C. (Csilla), Vijai, J. (Joseph), Jacobs, L. (Lauren), Corines, M. (Marina), Lincoln, A. (Anne), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Berger, R. (Raanan), Laitman, Y. (Yael), Rantala, J. (Johanna), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Borg, Å. (Åke), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Simard, J. (Jacques), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis), Kuchenbaecker, K.B. (Karoline), Neuhausen, S.L. (Susan), Robson, M. (Mark), Barrowdale, D. (Daniel), McGuffog, L. (Lesley), Mulligan, A.M. (Anna Marie), Andrulis, I.L. (Irene), Spurdle, A.B. (Amanda), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Engel, C. (Christoph), Wapenschmidt, B. (Barbara), Nevanlinna, H. (Heli), Thomassen, M. (Mads), Southey, M.C. (Melissa), Radice, P. (Paolo), Ramus, S.J. (Susan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Lee, A. (Andrew), Healey, S. (Sue), Nussbaum, R. (Robert), Rebbeck, R. (Timothy), Arun, B.K. (Banu), James, M. (Margaret), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Cass, I. (Ilana), Terry, M.B. (Mary Beth), Daly, M.J. (Mark), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Overeem Hansen, T. (Thomas) van, Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Nielsen, F. (Finn), Dennis, J. (Joe), Cunningham, J.M. (Julie), Hart, S. (Stewart), Slager, S. (Susan), Osorio, A. (Ana), Benítez, J. (Javier), Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Tafur, I. (Isaac), Hander, M. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Roversi, G. (Gaia), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariani, P. (Paolo), Volorio, S. (Sara), Dolcetti, R. (Riccardo), Varesco, L. (Liliana), Papi, L. (Laura), Tibiletti, M.G. (Maria Grazia), Giannini, G. (Giuseppe), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Ong, K., Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Godwin, A.K. (Andrew), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Steinemann, D. (Doris), Bogdanova-Markov, N. (Nadja), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Gehrig, P.A. (Paola A.), Markiefka, B. (Birgid), Buecher, B. (Bruno), Lefol, C. (Cédrick), Stoppa-Lyonnet, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Barjhoux, L. (Laure), Faivre, L. (Laurence), Longy, M. (Michel), Sevenet, N. (Nicolas), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Caux-Moncoutier, V. (Virginie), Isaacs, C. (Claudine), Van Maerken, T. (Tom), Claes, K.B.M. (Kathleen B.M.), Piedmonte, M. (Marion), Andrews, L. (Lesley), Hays, J. (John), Rodriguez, G.C. (Gustavo), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Khan, S. (Sofia), Hogervorst, F.B.L. (Frans), Aalfs, C.M. (Cora), Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Wijnen, J.T. (Juul), Roozendaal, K.E. (Kees) van, Mensenkamp, A.R. (Arjen), Ouweland, A.M.W. (Ans) van den, Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Lubinski, J. (Jan), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Arason, A. (Adalgeir), Maugard, C., Soucy, P. (Penny), Montagna, M. (Marco), Agata, S. (Simona), Teixeira, P.J., Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Hallberg, B. (Boubou), Wang, X. (Xianshu), Szabo, C. (Csilla), Vijai, J. (Joseph), Jacobs, L. (Lauren), Corines, M. (Marina), Lincoln, A. (Anne), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Berger, R. (Raanan), Laitman, Y. (Yael), Rantala, J. (Johanna), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Borg, Å. (Åke), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Simard, J. (Jacques), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus), and Antoniou, A.C. (Antonis)
Abstract: Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive ass
Published: 2014
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63. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Kuchenbaecker, KB, Neuhausen, SL, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Ramus, SJ, Domchek, SM, Nathanson, KL, Nussbaum, RL, Rebbeck, TR, Arun, BK, Karlan, BY, Breast Cancer Family Registry, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Dorfling, CM, van Rensburg, EJ, Gerdes, AM, Nielsen, FC, Weitzel, JN, ROVERSI, GAIA, Tibiletti, MG, Evans, DG, EMBRACE Study, Ong, KR, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Godwin, AK, GEMO Study Collaborators, Sinilnikova, OM, Rodriguez, GC, Hogervorst, FB, Aalfs, CM, de Lange, JL, Meijers Heijboer, HE, van der Hout, AH, Wijnen, JT, van Roozendaal, KE, Mensenkamp, AR, van den Ouweland, AM, van Deurzen, CH, van der Luijt, RB, HEBON, Teixeira, MR, KConFab, Investigators, Pankratz, VS, Szabo, CI, Singer, CF, Kaulich, DG, Tea, MK, Phelan, CM, Mai, PL, Greene, MH, Imyanitov, EN, Toland, AE, Pedersen, IS, Jensen, UB, Caligo, MA, Olopade, OI, Easton, DF, Couch, FJ, Antoniou, AC, CIMBA, Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Kuchenbaecker, KB, Neuhausen, SL, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Ramus, SJ, Domchek, SM, Nathanson, KL, Nussbaum, RL, Rebbeck, TR, Arun, BK, Karlan, BY, Breast Cancer Family Registry, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Dorfling, CM, van Rensburg, EJ, Gerdes, AM, Nielsen, FC, Weitzel, JN, ROVERSI, GAIA, Tibiletti, MG, Evans, DG, EMBRACE Study, Ong, KR, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Godwin, AK, GEMO Study Collaborators, Sinilnikova, OM, Rodriguez, GC, Hogervorst, FB, Aalfs, CM, de Lange, JL, Meijers Heijboer, HE, van der Hout, AH, Wijnen, JT, van Roozendaal, KE, Mensenkamp, AR, van den Ouweland, AM, van Deurzen, CH, van der Luijt, RB, HEBON, Teixeira, MR, KConFab, Investigators, Pankratz, VS, Szabo, CI, Singer, CF, Kaulich, DG, Tea, MK, Phelan, CM, Mai, PL, Greene, MH, Imyanitov, EN, Toland, AE, Pedersen, IS, Jensen, UB, Caligo, MA, Olopade, OI, Easton, DF, Couch, FJ, Antoniou, AC, and CIMBA
Abstract: Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC)=0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC=0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC=0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10-6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Con
Published: 2014

64. The genetics of inherited predispositions to colorectal polyps: a quick guide for clinicians

Author: Ricci, M. T., primary, Salemme, M., additional, Villanacci, V., additional, and Varesco, L., additional
Published: 2014
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65. The familial adenomatous polyposis region exhibits many different haplotypes

Author: STELLA A., RESTA N., POLIZZI A, MONTERA M., CARIOLA F, SUSCA F., GENTILE M, SALA P, VARESCO L., MARENI C., GUANTI G., IZZO, PAOLA, Stella, A., Resta, N., Polizzi, A, Montera, M., Cariola, F, Susca, F., Izzo, Paola, Gentile, M, Sala, P, Varesco, L., Mareni, C., and Guanti, G.
Published: 1998

66. Genetica e oncologia: implicazioni relazionali e di gestione del paziente

Author: Crotti, N, Broglia, V, Gianetti, C, Pronzato, P, Aglietta, Massimo, DALLA PICCOLA, B, Galligoni, E, Marangolo, M, Pierotti, M, and Varesco, L.
Published: 2007

67. Increased Risk of Colorectal Adenomas in Italian Subjects Carrying the p53 PIN3 A2-Pro72 Haplotype

Author: Perfumo, C, Bonelli, L, Menichini, P, Inga, A, Gismondi, V, Ciferri, E, Percivale, P, Bianchi, Giovanna, Nasti, Sabina, Fronza, G, and Varesco, L.
Published: 2007

68. 962: Association of SULT1A1 Arg213His polymorphism with male breast cancer risk: a case−control study in Italy

Author: Rizzolo, P., primary, Silvestri, V., additional, Giannini, G., additional, Varesco, L., additional, Viel, A., additional, Cortesi, L., additional, Montagna, M., additional, Radice, P., additional, Palli, D., additional, and Ottini, L., additional
Published: 2014
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69. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk.

Author: Couch, F.J., Wang, X., McGuffog, L., Lee, A., Olswold, C., Kuchenbaecker, K.B., Soucy, P., Fredericksen, Z., Barrowdale, D., Dennis, J., Gaudet, M.M., Dicks, E., Kosel, M., Healey, S., Sinilnikova, O.M., Bacot, F., Vincent, D., Hogervorst, F.B., Peock, S., Stoppa-Lyonnet, D., Jakubowska, A., Radice, P., Schmutzler, R.K., Domchek, S.M., Piedmonte, M., Singer, C.F., Friedman, E., Thomassen, M., Hansen, T.V., 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., Rensburg, E.J. van, 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., Hout, A.H. van der, Deurzen, C.H. van, Seynaeve, C., Gomez Garcia, E.B., Leeuwen, F.E. van, Meijers-Heijboer, H.E., Gille, J.J.P., Ausems, M.G., Blok, M.J., Ligtenberg, M.J.L., Rookus, M.A., Devilee, P., Verhoef, S., Os, T.A. van, 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, L., 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., 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., Hoya, M. de la, 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., Lu, K.H., 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., et al., Couch, F.J., Wang, X., McGuffog, L., Lee, A., Olswold, C., Kuchenbaecker, K.B., Soucy, P., Fredericksen, Z., Barrowdale, D., Dennis, J., Gaudet, M.M., Dicks, E., Kosel, M., Healey, S., Sinilnikova, O.M., Bacot, F., Vincent, D., Hogervorst, F.B., Peock, S., Stoppa-Lyonnet, D., Jakubowska, A., Radice, P., Schmutzler, R.K., Domchek, S.M., Piedmonte, M., Singer, C.F., Friedman, E., Thomassen, M., Hansen, T.V., 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., Rensburg, E.J. van, 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., Hout, A.H. van der, Deurzen, C.H. van, Seynaeve, C., Gomez Garcia, E.B., Leeuwen, F.E. van, Meijers-Heijboer, H.E., Gille, J.J.P., Ausems, M.G., Blok, M.J., Ligtenberg, M.J.L., Rookus, M.A., Devilee, P., Verhoef, S., Os, T.A. van, 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, L., 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., 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., Hoya, M. de la, 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., Lu, K.H., 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., and et al.
Abstract: 01 maart 2013, Contains fulltext : 115394.pdf (publisher's version ) (Open Access), 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 = 2.7x10(-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 = 1.4x10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4x10(-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 = 2x10(-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.
Published: 2013

70. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Author: Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), Dite, G.S. (Gillian), Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), and Dite, G.S. (Gillian)
Abstract: 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 associati
Published: 2013
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71. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Author: Hunter, KW, Couch, FJ, Wang, X, McGuffog, L, Lee, A, Olswold, C, Kuchenbaecker, KB, Soucy, P, Fredericksen, Z, Barrowdale, D, Dennis, J, Gaudet, MM, Dicks, E, Kosel, M, Healey, S, Sinilnikova, OM, Bacot, F, Vincent, D, Hogervorst, FBL, Peock, S, Stoppa-Lyonnet, D, Jakubowska, A, Radice, P, Schmutzler, RK, Domchek, SM, Piedmonte, M, Singer, CF, Friedman, E, Thomassen, M, Hansen, TVO, Neuhausen, SL, Szabo, CI, Blanco, I, Greene, MH, Karlan, BY, Garber, J, Phelan, CM, Weitzel, JN, Montagna, M, Olah, E, Andrulis, IL, Godwin, AK, Yannoukakos, D, Goldgar, DE, Caldes, T, Nevanlinna, H, Osorio, A, Terry, MB, Daly, MB, van Rensburg, EJ, Hamann, U, Ramus, SJ, Toland, AE, Caligo, MA, Olopade, OI, Tung, N, Claes, K, Beattie, MS, Southey, MC, Imyanitov, EN, Tischkowitz, M, Janavicius, R, John, EM, Kwong, A, Diez, O, Balmana, J, Barkardottir, RB, Arun, BK, Rennert, G, Teo, S-H, Ganz, PA, Campbell, I, van der Hout, AH, van Deurzen, CHM, Seynaeve, C, Garcia, EBG, van Leeuwen, FE, Meijers-Heijboer, HEJ, Gille, JJP, Ausems, MGEM, Blok, MJ, Ligtenberg, MJL, Rookus, MA, Devilee, P, Verhoef, S, van Os, TAM, Wijnen, JT, Frost, D, Ellis, S, Fineberg, E, Platte, R, Evans, DG, Izatt, L, Eeles, RA, Adlard, J, Eccles, DM, Cook, J, Brewer, C, Douglas, F, Hodgson, S, Morrison, PJ, Side, LE, Donaldson, A, Houghton, C, Rogers, MT, 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, AB, Viel, A, Peissel, B, Bonanni, B, Melloni, G, Ottini, L, Papi, L, Varesco, L, Tibiletti, MG, 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, BHF, Arver, B, Stenmark-Askmalm, M, Loman, N, Rosenquist, R, Einbeigi, Z, Nathanson, KL, Rebbeck, TR, Blank, SV, Cohn, DE, Rodriguez, GC, Small, L, Friedlander, M, Bae-Jump, VL, Fink-Retter, A, Rappaport, C, Gschwantler-Kaulich, D, Pfeiler, G, Tea, M-K, Lindor, NM, Kaufman, B, Paluch, SS, Laitman, Y, Skytte, A-B, Gerdes, A-M, Pedersen, IS, Moeller, ST, Kruse, TA, Jensen, UB, Vijai, J, Sarrel, K, Robson, M, Kauff, N, Mulligan, AM, Glendon, G, Ozcelik, H, Ejlertsen, B, Nielsen, FC, Jonson, L, Andersen, MK, Ding, YC, Steele, L, Foretova, L, Teule, A, Lazaro, C, Brunet, J, Angel Pujana, M, Mai, PL, Loud, JT, Walsh, C, Lester, J, Orsulic, S, Narod, SA, Herzog, J, Sand, SR, Tognazzo, S, Agata, S, Vaszko, T, Weaver, J, Stavropoulou, AV, Buys, SS, Romero, A, de la Hoya, M, Aittomaki, K, Muranen, TA, Duran, M, Chung, WK, Lasa, A, Dorfling, CM, Miron, A, Benitez, J, Senter, L, Huo, D, Chan, SB, Sokolenko, AP, Chiquette, J, Tihomirova, L, Friebel, TM, Agnarsson, BA, Lu, KH, Lejbkowicz, F, James, PA, Hall, P, Dunning, AM, Tessier, D, Cunningham, J, Slager, SL, Wang, C, Hart, S, Stevens, K, Simard, J, Pastinen, T, Pankratz, VS, Offit, K, Easton, DF, Chenevix-Trench, G, Antoniou, AC, Hunter, KW, Couch, FJ, Wang, X, McGuffog, L, Lee, A, Olswold, C, Kuchenbaecker, KB, Soucy, P, Fredericksen, Z, Barrowdale, D, Dennis, J, Gaudet, MM, Dicks, E, Kosel, M, Healey, S, Sinilnikova, OM, Bacot, F, Vincent, D, Hogervorst, FBL, Peock, S, Stoppa-Lyonnet, D, Jakubowska, A, Radice, P, Schmutzler, RK, Domchek, SM, Piedmonte, M, Singer, CF, Friedman, E, Thomassen, M, Hansen, TVO, Neuhausen, SL, Szabo, CI, Blanco, I, Greene, MH, Karlan, BY, Garber, J, Phelan, CM, Weitzel, JN, Montagna, M, Olah, E, Andrulis, IL, Godwin, AK, Yannoukakos, D, Goldgar, DE, Caldes, T, Nevanlinna, H, Osorio, A, Terry, MB, Daly, MB, van Rensburg, EJ, Hamann, U, Ramus, SJ, Toland, AE, Caligo, MA, Olopade, OI, Tung, N, Claes, K, Beattie, MS, Southey, MC, Imyanitov, EN, Tischkowitz, M, Janavicius, R, John, EM, Kwong, A, Diez, O, Balmana, J, Barkardottir, RB, Arun, BK, Rennert, G, Teo, S-H, Ganz, PA, Campbell, I, van der Hout, AH, van Deurzen, CHM, Seynaeve, C, Garcia, EBG, van Leeuwen, FE, Meijers-Heijboer, HEJ, Gille, JJP, Ausems, MGEM, Blok, MJ, Ligtenberg, MJL, Rookus, MA, Devilee, P, Verhoef, S, van Os, TAM, Wijnen, JT, Frost, D, Ellis, S, Fineberg, E, Platte, R, Evans, DG, Izatt, L, Eeles, RA, Adlard, J, Eccles, DM, Cook, J, Brewer, C, Douglas, F, Hodgson, S, Morrison, PJ, Side, LE, Donaldson, A, Houghton, C, Rogers, MT, 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, AB, Viel, A, Peissel, B, Bonanni, B, Melloni, G, Ottini, L, Papi, L, Varesco, L, Tibiletti, MG, 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, BHF, Arver, B, Stenmark-Askmalm, M, Loman, N, Rosenquist, R, Einbeigi, Z, Nathanson, KL, Rebbeck, TR, Blank, SV, Cohn, DE, Rodriguez, GC, Small, L, Friedlander, M, Bae-Jump, VL, Fink-Retter, A, Rappaport, C, Gschwantler-Kaulich, D, Pfeiler, G, Tea, M-K, Lindor, NM, Kaufman, B, Paluch, SS, Laitman, Y, Skytte, A-B, Gerdes, A-M, Pedersen, IS, Moeller, ST, Kruse, TA, Jensen, UB, Vijai, J, Sarrel, K, Robson, M, Kauff, N, Mulligan, AM, Glendon, G, Ozcelik, H, Ejlertsen, B, Nielsen, FC, Jonson, L, Andersen, MK, Ding, YC, Steele, L, Foretova, L, Teule, A, Lazaro, C, Brunet, J, Angel Pujana, M, Mai, PL, Loud, JT, Walsh, C, Lester, J, Orsulic, S, Narod, SA, Herzog, J, Sand, SR, Tognazzo, S, Agata, S, Vaszko, T, Weaver, J, Stavropoulou, AV, Buys, SS, Romero, A, de la Hoya, M, Aittomaki, K, Muranen, TA, Duran, M, Chung, WK, Lasa, A, Dorfling, CM, Miron, A, Benitez, J, Senter, L, Huo, D, Chan, SB, Sokolenko, AP, Chiquette, J, Tihomirova, L, Friebel, TM, Agnarsson, BA, Lu, KH, Lejbkowicz, F, James, PA, Hall, P, Dunning, AM, Tessier, D, Cunningham, J, Slager, SL, Wang, C, Hart, S, Stevens, K, Simard, J, Pastinen, T, Pankratz, VS, Offit, K, Easton, DF, Chenevix-Trench, G, and Antoniou, AC
Abstract: 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.
Published: 2013

72. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Author: Couch, FJ, Wang, XS, Olswold, C, Kuchenbaecker, KB, Soucy, P, Fredericksen, Z, Barrowdale, D, Dennis, J, Gaudet, MM, Dicks, E, Kosel, M, Healey, S, Sinilnikova, OM, van der Lee, A, Bacot, F, Vincent, D, Hogervorst, FBL, Peock, S, Stoppa-Lyonnet, D, Jakubowska, A, Radice, P, Schmutzler, RK, Domchek, SM, Piedmonte, M, Singer, CF, Friedman, E, Thomassen, Marga, Hansen, TVO, Neuhausen, SL, Szabo, CI, Blanco, I, Greene, MH, Karlan, BY, Garber, J, Phelan, CM, Weitzel, JN, Montagna, M, Olah, E, Andrulis, IL, Godwin, AK, Yannoukakos, D, Goldgar, DE, Caldes, T, Nevanlinna, H, Osorio, A, Terry, MB, Daly, MB, van Rensburg, EJ, Hamann, U, Ramus, SJ, Toland, AE, Caligo, MA, Olopade, OI, Tung, N, Claes, K, Beattie, MS, Southey, MC, Imyanitov, EN, Tischkowitz, M, Janavicius, R, John, EM, Kwong, A, Diez, O, Balmana, J, Barkardottir, RB, Arun, BK, Rennert, G, Teo, SH, Ganz, PA, Campbell, I, van der Hout, AH, van Deurzen, Carolien, Seynaeve, Caroline, Garcia, EBG, van Leeuwen, FE, Meijers-Heijboer, HEJ, Gille, JJP, Ausems, MGEM, Blok, MJ, Ligtenberg, MJL, Rookus, MA, Devilee, P, Verhoef, S, van Os, TAM, Wijnen, JT, Frost, D, Ellis, S, Fineberg, E, Platte, R, Evans, DG, Izatt, L, Eeles, RA, Adlard, J, Eccles, DM, Cook, J, Brewer, C, Douglas, F, Hodgson, S, Morrison, PJ, Side, LE, Donaldson, A, Houghton, C, Rogers, MT, 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, YJ, Zlowocka-Perlowska, E, Gronwald, J, Lubinski, J, Durda, K, Jaworska, K, Huzarski, T, Spurdle, AB, Viel, A, Peissel, B, Bonanni, B, Melloni, G, Ottini, L, Papi, L, Varesco, L, Tibiletti, MG, 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, BHF, Arver, B, Stenmark-Askmalm, M, Loman, N, Rosenquist, R, Einbeigi, Z, Nathanson, KL, Rebbeck, TR, Blank, SV, Cohn, DE, Rodriguez, GC, Small, L, Friedlander, M, Bae-Jump, VL, Fink-Retter, A, Rappaport, C, Gschwantler-Kaulich, D, Pfeiler, G, Tea, MK, Lindor, NM, Kaufman, B, Paluch, SS, Laitman, Y, Skytte, AB, Gerdes, AM, Pedersen, IS, Moeller, ST, Kruse, TA, Jensen, UB, Vijai, J, Sarrel, K, Robson, M, Kauff, N, Mulligan, AM, Glendon, G, Ozcelik, H, Ejlertsen, B, Nielsen, FC, Jonson, L, Andersen, MK, Ding, YC, Steele, L, Foretova, L, Teule, A, Lazaro, C (Conxi), Brunet, J, Pujana, MA, Mai, PL, Loud, JT, Walsh, C, Lester, J, Orsulic, S, Narod, SA, Herzog, J, Sand, SR, Tognazzo, S, Agata, S, Vaszko, T, Weaver, J, Stavropoulou, AV, Buys, SS, Romero, A, de la Hoya, M, Aittomaki, K, Muranen, TA, Duran, M (Mercedes), Chung, WK, Lasa, A, Dorfling, CM, Miron, A, Benitez, J, Senter, L, Huo, DZ, Chan, SB, Sokolenko, AP, Chiquette, J, Tihomirova, L, Friebel, TM, Agnarsson, BA, Lu, KH, Lejbkowicz, F, James, PA, Hall, P, Dunning, AM, Tessier, D, Cunningham, J, Slager, SL, Wang, C, Hart, S, Stevens, K, Simard, J, Pastinen, T, Pankratz, VS, Offit, K, Easton, DF, Chenevix-Trench, G, Antoniou, AC, Couch, FJ, Wang, XS, Olswold, C, Kuchenbaecker, KB, Soucy, P, Fredericksen, Z, Barrowdale, D, Dennis, J, Gaudet, MM, Dicks, E, Kosel, M, Healey, S, Sinilnikova, OM, van der Lee, A, Bacot, F, Vincent, D, Hogervorst, FBL, Peock, S, Stoppa-Lyonnet, D, Jakubowska, A, Radice, P, Schmutzler, RK, Domchek, SM, Piedmonte, M, Singer, CF, Friedman, E, Thomassen, Marga, Hansen, TVO, Neuhausen, SL, Szabo, CI, Blanco, I, Greene, MH, Karlan, BY, Garber, J, Phelan, CM, Weitzel, JN, Montagna, M, Olah, E, Andrulis, IL, Godwin, AK, Yannoukakos, D, Goldgar, DE, Caldes, T, Nevanlinna, H, Osorio, A, Terry, MB, Daly, MB, van Rensburg, EJ, Hamann, U, Ramus, SJ, Toland, AE, Caligo, MA, Olopade, OI, Tung, N, Claes, K, Beattie, MS, Southey, MC, Imyanitov, EN, Tischkowitz, M, Janavicius, R, John, EM, Kwong, A, Diez, O, Balmana, J, Barkardottir, RB, Arun, BK, Rennert, G, Teo, SH, Ganz, PA, Campbell, I, van der Hout, AH, van Deurzen, Carolien, Seynaeve, Caroline, Garcia, EBG, van Leeuwen, FE, Meijers-Heijboer, HEJ, Gille, JJP, Ausems, MGEM, Blok, MJ, Ligtenberg, MJL, Rookus, MA, Devilee, P, Verhoef, S, van Os, TAM, Wijnen, JT, Frost, D, Ellis, S, Fineberg, E, Platte, R, Evans, DG, Izatt, L, Eeles, RA, Adlard, J, Eccles, DM, Cook, J, Brewer, C, Douglas, F, Hodgson, S, Morrison, PJ, Side, LE, Donaldson, A, Houghton, C, Rogers, MT, 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, YJ, Zlowocka-Perlowska, E, Gronwald, J, Lubinski, J, Durda, K, Jaworska, K, Huzarski, T, Spurdle, AB, Viel, A, Peissel, B, Bonanni, B, Melloni, G, Ottini, L, Papi, L, Varesco, L, Tibiletti, MG, 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, BHF, Arver, B, Stenmark-Askmalm, M, Loman, N, Rosenquist, R, Einbeigi, Z, Nathanson, KL, Rebbeck, TR, Blank, SV, Cohn, DE, Rodriguez, GC, Small, L, Friedlander, M, Bae-Jump, VL, Fink-Retter, A, Rappaport, C, Gschwantler-Kaulich, D, Pfeiler, G, Tea, MK, Lindor, NM, Kaufman, B, Paluch, SS, Laitman, Y, Skytte, AB, Gerdes, AM, Pedersen, IS, Moeller, ST, Kruse, TA, Jensen, UB, Vijai, J, Sarrel, K, Robson, M, Kauff, N, Mulligan, AM, Glendon, G, Ozcelik, H, Ejlertsen, B, Nielsen, FC, Jonson, L, Andersen, MK, Ding, YC, Steele, L, Foretova, L, Teule, A, Lazaro, C (Conxi), Brunet, J, Pujana, MA, Mai, PL, Loud, JT, Walsh, C, Lester, J, Orsulic, S, Narod, SA, Herzog, J, Sand, SR, Tognazzo, S, Agata, S, Vaszko, T, Weaver, J, Stavropoulou, AV, Buys, SS, Romero, A, de la Hoya, M, Aittomaki, K, Muranen, TA, Duran, M (Mercedes), Chung, WK, Lasa, A, Dorfling, CM, Miron, A, Benitez, J, Senter, L, Huo, DZ, Chan, SB, Sokolenko, AP, Chiquette, J, Tihomirova, L, Friebel, TM, Agnarsson, BA, Lu, KH, Lejbkowicz, F, James, PA, Hall, P, Dunning, AM, Tessier, D, Cunningham, J, Slager, SL, Wang, C, Hart, S, Stevens, K, Simard, J, Pastinen, T, Pankratz, VS, Offit, K, Easton, DF, Chenevix-Trench, G, and Antoniou, AC
Abstract: 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 x 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 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 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 x 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.
Published: 2013

73. Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: a retrospective study in a sample of Italian cancer genetics clinics

Author: Varesco, L, Viassolo, V, Viel, A, Gismondi, V, Radice, P, Montagna, M, Alducci, E, Della Puppa, L, Oliani, C, Tommasi, S, Caligo, Ma, Vivanet, C, Zuradelli, M, Mandich, P, Tibiletti, Mg, Cavalli, P, Lucci Cordisco, E, Turchetti, D, Boggiani, D, Bracci, R, Bruzzi, P, Bonelli, L, Lucci Cordisco, E (ORCID:0000-0002-6279-7604), Varesco, L, Viassolo, V, Viel, A, Gismondi, V, Radice, P, Montagna, M, Alducci, E, Della Puppa, L, Oliani, C, Tommasi, S, Caligo, Ma, Vivanet, C, Zuradelli, M, Mandich, P, Tibiletti, Mg, Cavalli, P, Lucci Cordisco, E, Turchetti, D, Boggiani, D, Bracci, R, Bruzzi, P, Bonelli, L, and Lucci Cordisco, E (ORCID:0000-0002-6279-7604)
Abstract: To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA genetic testing.
Published: 2013

74. The policy of public health genomics in Italy

Author: Simone, B, Mazzucco, W, Gualano, M, Agodi, A, Coviello, D, Bricarelli, F, Dallapiccola, B, Di Maria, E, Federici, A, Genuardi, Maurizio, Varesco, L, Ricciardi, W, Boccia, Stefania, Genuardi, Maurizio (ORCID:0000-0002-7410-8351), Boccia, S. (ORCID:0000-0002-1864-749X), Simone, B, Mazzucco, W, Gualano, M, Agodi, A, Coviello, D, Bricarelli, F, Dallapiccola, B, Di Maria, E, Federici, A, Genuardi, Maurizio, Varesco, L, Ricciardi, W, Boccia, Stefania, Genuardi, Maurizio (ORCID:0000-0002-7410-8351), and Boccia, S. (ORCID:0000-0002-1864-749X)
Abstract: Italy has a monitoring system for genetic testing, consisting in a periodic census of clinical and laboratory activities performed in the country. The experience is limited, however, concerning the translation of genomic testing for complex diseases into clinical practice. For the first time the Italian Ministry of Health has introduced a policy strategic plan on genomics and predictive medicine within the 2010-2012 National Prevention Plan. This achievement was supported by the Italian Network for Public Health Genomics (GENISAP) and will likely contribute to the integration of public health genomics into health care in the country. Our experience might be of interest not only in Italy, but in other high-income countries, struggling to keep a healthy economy and healthy citizens. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Published: 2013

75. The policy of public health genomics in Italy

Author: Simone, Benedetto, Mazzucco, Walter, Gualano, Mr, Agodi, A, Coviello, Domenico, Dagna Bricarelli, F, Dallapiccola, B, Di Maria, E, Federici, A, Genuardi, Maurizio, Varesco, L, Ricciardi, Walter, Boccia, Stefania, Genuardi, Maurizio (ORCID:0000-0002-7410-8351), Ricciardi, Gualtiero (ORCID:0000-0002-5655-688X), Boccia, Stefania (ORCID:0000-0002-1864-749X), Simone, Benedetto, Mazzucco, Walter, Gualano, Mr, Agodi, A, Coviello, Domenico, Dagna Bricarelli, F, Dallapiccola, B, Di Maria, E, Federici, A, Genuardi, Maurizio, Varesco, L, Ricciardi, Walter, Boccia, Stefania, Genuardi, Maurizio (ORCID:0000-0002-7410-8351), Ricciardi, Gualtiero (ORCID:0000-0002-5655-688X), and Boccia, Stefania (ORCID:0000-0002-1864-749X)
Abstract: Italy has a monitoring system for genetic testing, consisting in a periodic census of clinical and laboratory activities performed in the country. The experience is limited, however, concerning the translation of genomic testing for complex diseases into clinical practice. For the first time the Italian Ministry of Health has introduced a policy strategic plan on genomics and predictive medicine within the 2010-2012 National Prevention Plan. This achievement was supported by the Italian Network for Public Health Genomics (GENISAP) and will likely contribute to the integration of public health genomics into health care in the country. Our experience might be of interest not only in Italy, but in other high-income countries, struggling to keep a healthy economy and healthy citizens.
Published: 2013

76. Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: Results of an Italian multicenter study

Author: Resta, N, Pierannunzio, D, Lenato, Gm, Stella, A, Capocaccia, R, Bagnulo, R, Lastella, P, Susca, Fc, Bozzao, C, Loconte, Dc, Sabbà, C, Urso, E, Sala, P, Fornasarig, M, Grammatico, P, Piepoli, A, Host, C, Turchetti, D, Viel, A, Memo, L, Giunti, L, Stigliano, V, Varesco, L, Bertario, L, Genuardi, Maurizio, Lucci Cordisco, Emanuela, Tibiletti, Mg, Di Gregorio, C, Andriulli, A, Ponz De Leon, M., Genuardi, Maurizio (ORCID:0000-0002-7410-8351), Lucci Cordisco, Emanuela (ORCID:0000-0002-6279-7604), Resta, N, Pierannunzio, D, Lenato, Gm, Stella, A, Capocaccia, R, Bagnulo, R, Lastella, P, Susca, Fc, Bozzao, C, Loconte, Dc, Sabbà, C, Urso, E, Sala, P, Fornasarig, M, Grammatico, P, Piepoli, A, Host, C, Turchetti, D, Viel, A, Memo, L, Giunti, L, Stigliano, V, Varesco, L, Bertario, L, Genuardi, Maurizio, Lucci Cordisco, Emanuela, Tibiletti, Mg, Di Gregorio, C, Andriulli, A, Ponz De Leon, M., Genuardi, Maurizio (ORCID:0000-0002-7410-8351), and Lucci Cordisco, Emanuela (ORCID:0000-0002-6279-7604)
Abstract: BACKGROUND: Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various malignancies. We here report the results of the first Italian collaborative study on Peutz-Jeghers syndrome. AIMS: To assess cancer risks in a large homogenous cohort of patients with Peutz-Jeghers syndrome, carrying, in large majority, an identified STK11/LKB1 mutation. METHODS: One-hundred and nineteen patients with Peutz-Jeghers syndrome, ascertained in sixteen different Italian centres, were enrolled in a retrospective cohort study. Relative and cumulative cancer risks and genotype-phenotype correlations were evaluated. RESULTS: 36 malignant tumours were found in 31/119 (29 STK11/LKB1 mutation carriers) patients. The mean age at first cancer diagnosis was 41 years. The relative overall cancer risk was 15.1 with a significantly higher risk (p<0.001) in females (22.0) than in males (8.6). Highly increased relative risks were present for gastrointestinal (126.2) and gynaecological cancers (27.7), in particular for pancreatic (139.7) and cervical cancer (55.6). The Kaplan-Meier estimates for overall cumulative cancer risks were 20%, 43%, 71%, and 89%, at age 40, 50, 60 and 65 years, respectively. CONCLUSION: Peutz-Jeghers syndrome entails markedly elevated cancer risks, mainly for pancreatic and cervical cancers. This study provides a helpful reference for improving current surveillance protocols.
Published: 2013

77. Molecular characterization of RNASE6PL, a putative human tumor suppressor gene on chromosome 6q27

Author: Acquati, Francesco, Bianchi, M., Cinquetti, R., Campomenosi, Paola, Russo, A., Varesco, L., Possati, L., Tibiletti, M. G., Daidone, M. G., BARBANTI BRODANO, G., and Taramelli, R.
Published: 2002

78. 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

Author: Couch, F.J. (Fergus), Gaudet, M.M. (Mia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Wang, X. (Xing), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Healey, S. (Sue), Sinilnikova, O. (Olga), Andrulis, I.L. (Irene), Ozcelik, H. (Hilmi), Mulligan, A.M. (Anna Marie), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Kruse, T.A. (Torben), Caligo, M.A. (Maria), Wachenfeldt, A. (Anna) von, Barbany-Bustinza, G. (Gisela), Loman, N. (Niklas), Soller, M. (Maria), Ehrencrona, H. (Hans), Karlsson, P. (Per), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Zołwocka, E. (Elzbieta), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.I., Benítez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Os, T.A.M. (Theo) van, Leeuwen, F. (Fred) van, Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Blok, M.J. (Marinus), Kets, C.M. (Marleen), Hooning, M.J. (Maartje), Oldenburg, R.A. (Rogier), Ausems, M.G.E.M. (Margreet), Peock, S. (Susan), Frost, D. (Debra), Ellis, S.D. (Steve), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Jacobs, C. (Chris), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T.J. (Trevor), Cook, J. (Jackie), Paterson, J. (Joan), Brewer, C. (Carole), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Side, L. (Lucy), Bove, B. (B.), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Fassy-Colcombet, M. (Marion), Castera, L. (Laurent), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Pujol, P. (Pascal), Coupier, I. (Isabelle), Delnatte, C.D. (Capucine), Akloul, L. (Linda), Lynch, H. (Henry), Snyder, C.L. (Carrie), Buys, S.S. (Saundra), Daly, M.B. (Mary), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Hopper, J.L. (John), Goldgar, D. (David), Singer, C.F. (Christian), Rappaport, C. (Christine), Tea, M.-K., Fink-Retter, A. (Anneliese), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Arason, A. (Adalgeir), Vijai, J. (Joseph), Shah, S. (Sonia), Sarrel, K. (Kara), Robson, M. (Mark), Piedmonte, M. (Marion), Phillips, K. (Kelly), Basil, J. (Jack), Rubinstein, W.S. (Wendy), Boggess, J.F. (John), Wakeley, K. (Katie), Ewart-Toland, A. (Amanda), Montagna, M. (Marco), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Feliubadaló, L. (L.), Brunet, J. (Joan), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Odunsi, K. (Kunle), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E., Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Dorfling, C.M. (Cecelia), Diez, O. (Orland), Kwong, A. (Ava), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Heidemann, S. (Simone), Niederacher, D. (Dieter), Preisler-Adams, S. (Sabine), Gadzicki, D. (Dorothea), Varon-Mateeva, R. (Raymonda), Deissler, H. (Helmut), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Kast, K. (Karin), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Muranen, T.A. (Taru), Nevanlinna, H. (Heli), Tischkowitz, M. (Marc), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Lindor, N.M. (Noralane), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Bernard, L. (Loris), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Varesco, L. (Liliana), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Simard, J. (Jacques), Couch, F.J. (Fergus), Gaudet, M.M. (Mia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Wang, X. (Xing), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Healey, S. (Sue), Sinilnikova, O. (Olga), Andrulis, I.L. (Irene), Ozcelik, H. (Hilmi), Mulligan, A.M. (Anna Marie), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Kruse, T.A. (Torben), Caligo, M.A. (Maria), Wachenfeldt, A. (Anna) von, Barbany-Bustinza, G. (Gisela), Loman, N. (Niklas), Soller, M. (Maria), Ehrencrona, H. (Hans), Karlsson, P. (Per), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Zołwocka, E. (Elzbieta), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.I., Benítez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Os, T.A.M. (Theo) van, Leeuwen, F. (Fred) van, Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Blok, M.J. (Marinus), Kets, C.M. (Marleen), Hooning, M.J. (Maartje), Oldenburg, R.A. (Rogier), Ausems, M.G.E.M. (Margreet), Peock, S. (Susan), Frost, D. (Debra), Ellis, S.D. (Steve), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Jacobs, C. (Chris), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T.J. (Trevor), Cook, J. (Jackie), Paterson, J. (Joan), Brewer, C. (Carole), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Side, L. (Lucy), Bove, B. (B.), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Fassy-Colcombet, M. (Marion), Castera, L. (Laurent), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Pujol, P. (Pascal), Coupier, I. (Isabelle), Delnatte, C.D. (Capucine), Akloul, L. (Linda), Lynch, H. (Henry), Snyder, C.L. (Carrie), Buys, S.S. (Saundra), Daly, M.B. (Mary), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Hopper, J.L. (John), Goldgar, D. (David), Singer, C.F. (Christian), Rappaport, C. (Christine), Tea, M.-K., Fink-Retter, A. (Anneliese), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Arason, A. (Adalgeir), Vijai, J. (Joseph), Shah, S. (Sonia), Sarrel, K. (Kara), Robson, M. (Mark), Piedmonte, M. (Marion), Phillips, K. (Kelly), Basil, J. (Jack), Rubinstein, W.S. (Wendy), Boggess, J.F. (John), Wakeley, K. (Katie), Ewart-Toland, A. (Amanda), Montagna, M. (Marco), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Feliubadaló, L. (L.), Brunet, J. (Joan), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Odunsi, K. (Kunle), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E., Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Dorfling, C.M. (Cecelia), Diez, O. (Orland), Kwong, A. (Ava), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Heidemann, S. (Simone), Niederacher, D. (Dieter), Preisler-Adams, S. (Sabine), Gadzicki, D. (Dorothea), Varon-Mateeva, R. (Raymonda), Deissler, H. (Helmut), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Kast, K. (Karin), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Muranen, T.A. (Taru), Nevanlinna, H. (Heli), Tischkowitz, M. (Marc), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Lindor, N.M. (Noralane), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Bernard, L. (Loris), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Varesco, L. (Liliana), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), and Simard, J. (Jacques)
Abstract: 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.Wealso 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.
Published: 2012
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79. Clinical features and genotype-phenotype correlations in 41 Italian families with adenomatosis coli

Author: Ponz Leon, M., Benatti, P., Percesepe, A., Cacciatore, A., Sassatelli, R., Bertoni, G., Sabadini, G., Varesco, L., Viviana Gismondi, Mareni, C., Montera, M., Di Gregorio, C., Landi, P., and Roncucci, L.
Subjects: Adult, Male, Phenotype, Adenomatous Polyposis Coli, Genotype, Italy, Mutation, Chromosome Mapping, Humans, Female, Pedigree
Abstract: Familial Adenomatous Polyposis in an autosomal dominant disease in which the large bowel is carpeted by polyps of various dimensions appearing during the second or third decade of life. Several extracolonic manifestations complete the clinical spectrum of Familial Adenomatous Polyposis. If untreated, the disease leads invariably to colorectal cancer. The gene responsible for the disease, adenomatous Polyposis Coli, has been localized at chromosome 5q21.To describe the clinical features of 156 Familial Adenomatous Polyposis patients (from 41 families) and to analyze possible correlations between genotype and phenotype.Familial Adenomatous Polyposis was defined as the presence of 100 or more polyps in the large bowel. In 17 families (41%), the proband was the only affected individual (single cases). Adenomatous Polyposis Coli gene mutations were studied on DNA extracted from peripheral white blood cells and evaluated by polymerase chain reaction single strand conformation polymorphism, followed by direct sequencing of samples showing abnormal banding at single strand conformation polymorphism.The large majority of Familial Adenomatous Polyposis patients underwent surgery; colectomy with ileorectal anastomosis was the most frequent approach, however, cancer of the rectal stump developed in 11.6% of patients submitted to colectomy and ileorectal anastomosis. Adenomas were rare in the stomach (8.8%), but their frequency increased in the duodenum (33.8%) and jejunum (55.0%, chi 2 for trend 23.7, p0.001). Desmoid tumours were diagnosed in 17 patients (10.9% of the total) and in 6 families. Mutations of the Adenomatous Polyposis Coli gene were studied in 20 out of 25 families (80%) and on a total of 75 individuals. The most frequent alterations were 1 to 5 bp deletions leading to stop codons and truncated proteins. Desmoid tumours, presence of duodenal or jejunal adenomas were associated with an ample range of mutations, from codon 215 to codon 1464. In contrast, particularly severe polyposis (mean age at appearance of polyps 11-16 years, and of cancer development 27-32 years) was associated with a "hotspot" mutation site at codons 1303-1309.In patients with Familial Adenomatous Polyposis, subtotal colectomy with ileorectal anastomosis is still the treatment of choice. Adenomatous lesions seem to show a "gradient" distribution from the stomach to the large bowel. Desmoid tumours are relatively common, though their incidence is limited to some of the families. Constitutional mutations can be detected in 80% of the investigated families. Genotype-phenotype correlations showed a hot-spot at codons 1303-1309, frequently associated with severe polyposis.
Published: 2000

80. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Antoniou, A.C., Kartsonaki, C., Sinilnikova, O.M., Soucy, P., McGuffog, L., Healey, S., Lee, A., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Barile, M., Pensotti, V., Pasini, B., Dolcetti, R., Giannini, G., Putignano, A.L., Varesco, L., Radice, P., Mai, P.L., Greene, M.H., Andrulis, I.L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A.M., Kruse, T.A., Birk Jensen, U., Cruger, D.G., Caligo, M.A., Laitman, Y., Milgrom, R., Kaufman, B., Paluch-Shimon, S., Friedman, E., Loman, N., Harbst, K., Lindblom, A., Arver, B., Ehrencrona, H., Melin, B., Nathanson, K.L., Domchek, S.M., Rebbeck, T., Jakubowska, A., Lubinski, J., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Gorski, B., Osorio, A., Ramon Y Cajal, T., Fostira, F., Andres, R., Benitez, J., Hamann, U., Hogervorst, F.B.L., Rookus, M.A., Hooning, M.J., Nelen, M.R., Luijt, R.B. van der, Os, T.A. van, Asperen, C.J. van, Devilee, P., Meijers-Heijboer, H.E., Garcia, E.B., Peock, S., Cook, M., Frost, D., Platte, R., Leyland, J., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Eccles, D., Ong, K.R., Cook, J., Douglas, F., Paterson, J., Kennedy, M.J., Miedzybrodzka, Z., Godwin, A., Stoppa-Lyonnet, D., Buecher, B., Belotti, M., Tirapo, C., Mazoyer, S., Barjhoux, L., Lasset, C., Leroux, D., Faivre, L., Bronner, M., Prieur, F., Nogues, C., Rouleau, E., et al., Antoniou, A.C., Kartsonaki, C., Sinilnikova, O.M., Soucy, P., McGuffog, L., Healey, S., Lee, A., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Barile, M., Pensotti, V., Pasini, B., Dolcetti, R., Giannini, G., Putignano, A.L., Varesco, L., Radice, P., Mai, P.L., Greene, M.H., Andrulis, I.L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A.M., Kruse, T.A., Birk Jensen, U., Cruger, D.G., Caligo, M.A., Laitman, Y., Milgrom, R., Kaufman, B., Paluch-Shimon, S., Friedman, E., Loman, N., Harbst, K., Lindblom, A., Arver, B., Ehrencrona, H., Melin, B., Nathanson, K.L., Domchek, S.M., Rebbeck, T., Jakubowska, A., Lubinski, J., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Gorski, B., Osorio, A., Ramon Y Cajal, T., Fostira, F., Andres, R., Benitez, J., Hamann, U., Hogervorst, F.B.L., Rookus, M.A., Hooning, M.J., Nelen, M.R., Luijt, R.B. van der, Os, T.A. van, Asperen, C.J. van, Devilee, P., Meijers-Heijboer, H.E., Garcia, E.B., Peock, S., Cook, M., Frost, D., Platte, R., Leyland, J., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Eccles, D., Ong, K.R., Cook, J., Douglas, F., Paterson, J., Kennedy, M.J., Miedzybrodzka, Z., Godwin, A., Stoppa-Lyonnet, D., Buecher, B., Belotti, M., Tirapo, C., Mazoyer, S., Barjhoux, L., Lasset, C., Leroux, D., Faivre, L., Bronner, M., Prieur, F., Nogues, C., Rouleau, E., and et al.
Abstract: Item does not contain fulltext, Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
Published: 2011

81. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Antoniou, A.C. (Antonis), Kartsonaki, C. (Christiana), Sinilnikova, O. (Olga), Soucy, P. (Penny), McGuffog, L. (Lesley), Healey, S. (Sue), Lee, A. (Andrew), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Cattaneo, E. (Elisa), Barile, M. (Monica), Pensotti, V. (Valeria), Pasini, B. (Barbara), Dolcetti, R. (Riccardo), Giannini, G. (Giuseppe), Putignano, A.L., Varesco, L. (Liliana), Radice, P. (Paolo), Mai, P.L. (Phuong), Greene, M.H. (Mark), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Jensen, U.B., Cruger, D. (Dorthe), Caligo, M.A. (Maria), Laitman, Y. (Yael), Milgrom, R. (Roni), Kaufman, B. (Bella), Paluch-Shimon, S. (Shani), Friedman, E. (Eitan), Loman, N. (Niklas), Harbst, K. (Katja), Lindblom, A. (Annika), Melin, B. (Beatrice), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Cajal, T.R., Fostira, F. (Florentia), Andres, R. (Raquel), Benitez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Rookus, M.A. (Matti), Hooning, M.J. (Maartje), Nelen, M.R. (Marcel), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Asperen, C.J. (Christi) van, Devilee, P. (Peter), Meijers-Heijboer, H. (Hanne), Garcia, E.B.G., Peock, S. (Susan), Cook, M. (Margaret), Frost, D., Platte, R. (Radka), Leyland, J. (Jean), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R., Douglas, F. (Fiona), Paterson, J. (Joan), Kennedy, M.J. (John), Miedzybrodzka, Z. (Zosia), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Buecher, B. (Bruno), Belotti, M. (Muriel), Tirapo, C. (Carole), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Lasset, C. (Christine), Leroux, D. (Dominique), Faivre, L. (Laurence), Bronner, M. (Myriam), Prieur, F. (Fabienne), Nogues, C. (Catherine), Rouleau, E. (Etienne), Pujol, P. (Pascal), Coupier, I. (Isabelle), Frenay, M. (Marc), Hopper, J. (John), Daly, M.J. (Mark), Terry, M-B. (Mary-beth), John, E.M. (Esther), Buys, S.S. (Saundra), Yassin, Y. (Yosuf), Miron, A. (Alexander), Goldgar, D. (David), Singer, C.F. (Christian), Tea, M.-K., Pfeiler, G. (Georg), Dressler, C. (Catherina), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Ejlertsen, B. (Bent), Barkardottir, R.B. (Rosa), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Piedmonte, M. (Marion), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Toland, A.E. (Amanda), Montagna, M. (Marco), Tognazzo, S. (Silvia), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Pharoah, P.D.P. (Paul), Sucheston, L. (Lara), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E. (Edith), Bozsik, A. (Aniko), Teo, S.-H. (Soo-Hwang), Seldon, J.L. (Joyce), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Sluiter, M.D. (Michelle), Diez, O. (Orland), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ruehl, I. (Ina), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Deissler, H. (Helmut), Niederacher, D. (Dieter), Arnold, N. (Norbert), Gadzicki, D. (Dorothea), Schönbuchner, I. (Ines), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Dumont, M. (Martine), Chiquette, J. (Jocelyne), Tischkowitz, M. (Marc), Chenevix-Trench, G. (Georgia), Beesley, J. (Jonathan), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Fredericksen, Z. (Zachary), Wang, X. (Xing), Pankratz, V.S. (Shane), Couch, F.J. (Fergus), Simard, J. (Jacques), Easton, D.F. (Douglas), Karlsson, P. (Per), Nordling, M. (Margareta), Bergman, A. (Annika), Einbeigi, Z. (Zakaria), Stenmark-Askmalm, M. (M.), Liedgren, S. (Sigrun), Borg, Å. (Åke), Olsson, H. (Hans), Kristoffersson, U. (Ulf), Jernström, H. (H.), Henriksson, K. (Karin), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Barbany-Bustinza, G. (Gisela), Rantala, J. (Johanna), Grönberg, H. (Henrik), Stattin, E.-L., Emanuelsson, M. (Monica), Brandell, R.R., Dahl, N. (Niklas), Verhoef, S., Verheus, M. (Martijn), Veer, L.J. (Laura) van 't, Leeuwen, F.E. (Flora) van, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Jager, A. (Agnes), Tilanus-Linthorst, M.M.A. (Madeleine), Seynaeve, C.M. (Caroline), Wijnen, J.T. (Juul), Vreeswijk, M.P. (Maaike), Tollenaar, R.A.E.M. (Rob), Ligtenberg, M.J. (Marjolijn), Hoogerbrugge, N. (Nicoline), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, J.J.P. (Jan), Waisfisz, Q. (Quinten), Gómez García, E.B. (Encarna), Roozendaal, C.E. (Cees) van, Blok, M.J. (Marinus), Caanen, B., Oosterwijk, J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J., Vasen, H.F. (Hans), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), McKeown, C. (Carole), Hoffman, J. (Jonathan), Donaldson, A. (Alan), Downing, S. (Sarah), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Hill, K. (Kathryn), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Whaite, A. (Anna), Dorkins, H. (Huw), Barwell, J. (Julian), Chu, C. (Chengbin), Miller, J. (Julie), Ellis, I.O. (Ian), Houghton, C. (Catherine), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), D'Mello, L. (Lucia), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Mitra, A. (Anita), Robertson, L. (Lisa), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Ehrencrona, H. (Hans), Hodgson, S.V. (Shirley), Barton, D.E. (David), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lucassen, A. (Anneke), Crawford, G. (Gillian), McBride, D. (Donna), Smalley, S. (Sarah), Adlard, J.W. (Julian), Arver, B. (Brita Wasteson), Antoniou, A.C. (Antonis), Kartsonaki, C. (Christiana), Sinilnikova, O. (Olga), Soucy, P. (Penny), McGuffog, L. (Lesley), Healey, S. (Sue), Lee, A. (Andrew), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Cattaneo, E. (Elisa), Barile, M. (Monica), Pensotti, V. (Valeria), Pasini, B. (Barbara), Dolcetti, R. (Riccardo), Giannini, G. (Giuseppe), Putignano, A.L., Varesco, L. (Liliana), Radice, P. (Paolo), Mai, P.L. (Phuong), Greene, M.H. (Mark), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Jensen, U.B., Cruger, D. (Dorthe), Caligo, M.A. (Maria), Laitman, Y. (Yael), Milgrom, R. (Roni), Kaufman, B. (Bella), Paluch-Shimon, S. (Shani), Friedman, E. (Eitan), Loman, N. (Niklas), Harbst, K. (Katja), Lindblom, A. (Annika), Melin, B. (Beatrice), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Cajal, T.R., Fostira, F. (Florentia), Andres, R. (Raquel), Benitez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Rookus, M.A. (Matti), Hooning, M.J. (Maartje), Nelen, M.R. (Marcel), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Asperen, C.J. (Christi) van, Devilee, P. (Peter), Meijers-Heijboer, H. (Hanne), Garcia, E.B.G., Peock, S. (Susan), Cook, M. (Margaret), Frost, D., Platte, R. (Radka), Leyland, J. (Jean), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R., Douglas, F. (Fiona), Paterson, J. (Joan), Kennedy, M.J. (John), Miedzybrodzka, Z. (Zosia), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Buecher, B. (Bruno), Belotti, M. (Muriel), Tirapo, C. (Carole), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Lasset, C. (Christine), Leroux, D. (Dominique), Faivre, L. (Laurence), Bronner, M. (Myriam), Prieur, F. (Fabienne), Nogues, C. (Catherine), Rouleau, E. (Etienne), Pujol, P. (Pascal), Coupier, I. (Isabelle), Frenay, M. (Marc), Hopper, J. (John), Daly, M.J. (Mark), Terry, M-B. (Mary-beth), John, E.M. (Esther), Buys, S.S. (Saundra), Yassin, Y. (Yosuf), Miron, A. (Alexander), Goldgar, D. (David), Singer, C.F. (Christian), Tea, M.-K., Pfeiler, G. (Georg), Dressler, C. (Catherina), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Ejlertsen, B. (Bent), Barkardottir, R.B. (Rosa), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Piedmonte, M. (Marion), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Toland, A.E. (Amanda), Montagna, M. (Marco), Tognazzo, S. (Silvia), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Pharoah, P.D.P. (Paul), Sucheston, L. (Lara), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E. (Edith), Bozsik, A. (Aniko), Teo, S.-H. (Soo-Hwang), Seldon, J.L. (Joyce), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Sluiter, M.D. (Michelle), Diez, O. (Orland), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ruehl, I. (Ina), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Deissler, H. (Helmut), Niederacher, D. (Dieter), Arnold, N. (Norbert), Gadzicki, D. (Dorothea), Schönbuchner, I. (Ines), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Dumont, M. (Martine), Chiquette, J. (Jocelyne), Tischkowitz, M. (Marc), Chenevix-Trench, G. (Georgia), Beesley, J. (Jonathan), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Fredericksen, Z. (Zachary), Wang, X. (Xing), Pankratz, V.S. (Shane), Couch, F.J. (Fergus), Simard, J. (Jacques), Easton, D.F. (Douglas), Karlsson, P. (Per), Nordling, M. (Margareta), Bergman, A. (Annika), Einbeigi, Z. (Zakaria), Stenmark-Askmalm, M. (M.), Liedgren, S. (Sigrun), Borg, Å. (Åke), Olsson, H. (Hans), Kristoffersson, U. (Ulf), Jernström, H. (H.), Henriksson, K. (Karin), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Barbany-Bustinza, G. (Gisela), Rantala, J. (Johanna), Grönberg, H. (Henrik), Stattin, E.-L., Emanuelsson, M. (Monica), Brandell, R.R., Dahl, N. (Niklas), Verhoef, S., Verheus, M. (Martijn), Veer, L.J. (Laura) van 't, Leeuwen, F.E. (Flora) van, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Jager, A. (Agnes), Tilanus-Linthorst, M.M.A. (Madeleine), Seynaeve, C.M. (Caroline), Wijnen, J.T. (Juul), Vreeswijk, M.P. (Maaike), Tollenaar, R.A.E.M. (Rob), Ligtenberg, M.J. (Marjolijn), Hoogerbrugge, N. (Nicoline), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, J.J.P. (Jan), Waisfisz, Q. (Quinten), Gómez García, E.B. (Encarna), Roozendaal, C.E. (Cees) van, Blok, M.J. (Marinus), Caanen, B., Oosterwijk, J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J., Vasen, H.F. (Hans), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), McKeown, C. (Carole), Hoffman, J. (Jonathan), Donaldson, A. (Alan), Downing, S. (Sarah), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Hill, K. (Kathryn), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Whaite, A. (Anna), Dorkins, H. (Huw), Barwell, J. (Julian), Chu, C. (Chengbin), Miller, J. (Julie), Ellis, I.O. (Ian), Houghton, C. (Catherine), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), D'Mello, L. (Lucia), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Mitra, A. (Anita), Robertson, L. (Lisa), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Ehrencrona, H. (Hans), Hodgson, S.V. (Shirley), Barton, D.E. (David), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lucassen, A. (Anneke), Crawford, G. (Gillian), McBride, D. (Donna), Smalley, S. (Sarah), Adlard, J.W. (Julian), and Arver, B. (Brita Wasteson)
Abstract: Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r2= 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10-9for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10-8for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
Published: 2011
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82. The CASP8 rs3834129 polymorphism and breast cancer risk in BRCA1 mutation carriers

Author: Catucci, I, Verderio, P, Pizzamiglio, S, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Ripamonti, C, Pasini, B, Barile, M, Viel, A, Giannini, G, Papi, L, Varesco, L, Martayan, A, Riboni, M, Volorio, S, Radice, P, Peterlongo, P, Ripamonti, CB, Peterlongo, P., ROVERSI, GAIA, Catucci, I, Verderio, P, Pizzamiglio, S, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Ripamonti, C, Pasini, B, Barile, M, Viel, A, Giannini, G, Papi, L, Varesco, L, Martayan, A, Riboni, M, Volorio, S, Radice, P, Peterlongo, P, Ripamonti, CB, Peterlongo, P., and ROVERSI, GAIA
Abstract: The rs3834129 polymorphism, in the promoter of CASP8 gene, has been recently reported as associated with breast cancer risk in the general population, with the minor allele del having a protective effect. Some of the genetic variants found associated with breast cancer risk were reported as risk modifiers in individuals with mutations in BRCA1 and BRCA2 genes. Here, we tested the effect of the rs3834129 del allele on breast cancer risk in BRCA mutation carriers. The rs3834129 was genotyped in a total of 1,207 Italian female BRCA mutation carriers. Of these, 740 carried a BRCA1 mutation and 467 a BRCA2 mutation. Overall, 699 were affected with breast cancer and 508 were unaffected. When considering class 1 (loss-of-function) BRCA mutations, hazard ratios estimated by weighted multivariable Cox regression model, for individuals with at least one copy of the del allele, were 1.46 (95% confidence interval (CI): 1.08-1.99) for BRCA1 and BRCA2 mutation carriers combined, 1.74 (95% CI: 1.24-2.46) for BRCA1 mutation carriers, and 1.09 (95% CI: 0.66-1.80) for BRCA2 mutation carriers. These results suggest that the minor allele del of rs3834129 is associated under a dominant model with increased breast cancer risk in carriers of BRCA1 mutations but not in carriers of BRCA2 mutations.
Published: 2011

83. F40 - TP53 germline mutation testing in early onset breast cancer

Author: Conte, B., Varesco, L., Iacono, G., Poggio, F., Blondeaux, E., Levaggi, A., D'Alonzo, A., Bighin, C., Giraudi, S., Vaglica, M., Pronzato, P., and Del Mastro, L.
Published: 2016
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84. Endometrial cancer and somatic G > T KRAS transversion in patients with constitutional MUTYH biallelic mutations

Author: Tricarico, R, Bettiol Furlan, Pierluigi, Ciambotti, B, Di Gregorio, Cristina, Gatteschi, B, Gismondi, V, Toschi, B, Tonelli, F, Varesco, L, Genuardi, Maurizio, Bet, P, Di Gregorio, C, Genuardi, M (ORCID:0000-0002-7410-8351), Tricarico, R, Bettiol Furlan, Pierluigi, Ciambotti, B, Di Gregorio, Cristina, Gatteschi, B, Gismondi, V, Toschi, B, Tonelli, F, Varesco, L, Genuardi, Maurizio, Bet, P, Di Gregorio, C, and Genuardi, M (ORCID:0000-0002-7410-8351)
Abstract: MUTYH-associated polyposis (MAP) is an autosomal recessive condition predisposing to colorectal cancer, caused by constitutional biallelic mutations in the base excision repair (BER) gene MUTYH. Colorectal tumours from MAP patients display an excess of somatic G>T mutations in the APC and KRAS genes due to defective BER function. To date, few extracolonic manifestations have been observed in MAP patients, and the clinical spectrum of this condition is not yet fully established. Recently, one patient with a diagnosis of endometrial cancer and biallelic MUTYH mutations has been described. We here report on two additional unrelated MAP patients with biallelic MUTYH germline mutations who developed endometrioid endometrial carcinoma. The endometrial tumours were evaluated for MEN, PIK3CA, KRAS, BRAF and CTNNB1 mutations. A G>T transversion at codon 12 of the KRAS gene was observed in one tumour. A single 1 bp frameshift deletion of PTEN was observed in the same sample. Overall, these findings suggest that endometrial carcinoma is a phenotypic manifestations of MAP and that inefficient repair of oxidative damage can be involved in its pathogenesis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
Published: 2009

85. The Italian National External Quality Assessment Program in Molecular Genetic Testing: Results of the VII Round (2010-2011)

Author: Censi, F., primary, Tosto, F., additional, Floridia, G., additional, Marra, M., additional, Salvatore, M., additional, Baffico, A. M., additional, Grasso, M., additional, Melis, M. A., additional, Pelo, E., additional, Radice, P., additional, Ravani, A., additional, Rosatelli, C., additional, Resta, N., additional, Russo, S., additional, Seia, M., additional, Varesco, L., additional, Falbo, V., additional, and Taruscio, D., additional
Published: 2013
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86. Identification and classification of hereditary nonpolyposis colorectal cancer (Lynch syndrome): Adapting old concepts to recent advancements. Report from the Italian association for the study of hereditary colorectal tumors consensus group

Author: de Leon, M, Bertario, L, Genuardi, M, Lanza, G, Oliani, C, Ranzani, G, Rossi, G, Varesco, L, Venesio, T, Viel, A, Genuardi, M (ORCID:0000-0002-7410-8351), Lanza, G (ORCID:0000-0003-2187-6653), de Leon, M, Bertario, L, Genuardi, M, Lanza, G, Oliani, C, Ranzani, G, Rossi, G, Varesco, L, Venesio, T, Viel, A, Genuardi, M (ORCID:0000-0002-7410-8351), and Lanza, G (ORCID:0000-0003-2187-6653)
Abstract: Knowledge about hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome clearly evolved during the last 10 to 15 years much more rapidly than in the past century. Consequently, long-established concepts and attitudes that held for many years should now be changed or updated. With regard to classification, we suggest maintaining the eponym "Lynch syndrome" for families that have a well-documented deficiency of the DNA mismatch repair system, whereas "clinical hereditary nonpolyposis colorectal cancer" should be reserved for those families that meet the Amsterdam criteria but without evidence of mismatch repair impairment. Any family (or individual) meeting one or more of the Bethesda criteria can be considered as suspected HNPCC. For the identification of hereditary colorectal cancer molecular screening or the pedigree analysis show advantages and disadvantages; the ideal would be to combine the two approaches. Diffusion of the microsatellite instability test and of immunohistochemistry in the pathology laboratories might render in the immediate future molecular screening more realistic. Strict endoscopic surveillance of family members at risk (with first colonoscopy at age 20-25 years and then every 2-3 years) is needed only in families with documented alterations of the DNA mismatch repair. To a certain extent, our conclusions were similar to the recently proposed "European guidelines for the clinical management of HNPCC," although we prefer the term "clinical hereditary nonpolyposis colorectal cancer," instead of familial colorectal cancer, for families meeting the Amsterdam criteria but not having evidence of mismatch repair impairment.
Published: 2007

87. Genotype-phenotype correlation in familial adenomatous polyposis (FAP): variation within and among families in 91 pedigrees of the Italian Registry

Author: Presciuttini, Silvano, Varesco, L, Sala, P, Gismondi, V, Radice, P, Giarola, M, Mareni, C, Aste, H, Marchese, C, de Leon MP, and Bertario, L.
Published: 1997

88. Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16

Author: Wijnen, J., Meera Khan, P., Vasen, H., Menko, F., Klift, H. D., Broek, M. D., Leeuwen-Cornelisse, I., Nagengast, F., Meijers-Heijboer, E. J., Dick Lindhout, Griffioen, G., Cats, A., Kleibeuker, J., Varesco, L., Bertario, L., Bisgaard, M. -L, Mohr, J., Kolodner, R., Fodde, R., Other departments, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Male, congenital, hereditary, and neonatal diseases and abnormalities, DNA Repair, Molecular Sequence Data, Polymerase Chain Reaction, GRADIENT GEL-ELECTROPHORESIS, Proto-Oncogene Proteins, Humans, GENETIC INSTABILITY, neoplasms, Germ-Line Mutation, Adaptor Proteins, Signal Transducing, DNA Primers, Genes, Dominant, SPECTRUM, Base Sequence, COLON-CANCER, Nuclear Proteins, nutritional and metabolic diseases, Exons, SINGLE-BASE CHANGES, Colorectal Neoplasms, Hereditary Nonpolyposis, digestive system diseases, Neoplasm Proteins, Pedigree, DNA-Binding Proteins, Europe, POLYPOSIS, HOMOLOG, MutS Homolog 2 Protein, Mutation, Electrophoresis, Polyacrylamide Gel, Female, Carrier Proteins, MutL Protein Homolog 1, Research Article
Abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer susceptibility condition. Inherited mutations in at least four DNA mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC. In this study we used denaturing gradient gel electrophoresis (DGGE) to screen for hMLH1 mutations in 34 unrelated HNPCC families (30 Dutch, 3 Italian, and 1 Danish). Ten novel pathogenic germ-line mutations (seven affecting splice sites, two frameshifts, and one in-frame deletion of a single amino acid) have been identified in 12 (35%) of these families. In a previous study, hMSH2 mutations were found in 21% of the same families. While the spectrum of mutations at the hMSH2 gene among HNPCC patients appears heterogeneous, a cluster of hMLH1 mutations has been found in the region encompassing exons 15 and 16, which accounts for 50% of all the independent hMLH1 mutations described to date and for > 20% of the unrelated HNPCC kindreds here analyzed. This unexpected finding has a great practical value in the clinical scenario of genetic services.
Published: 1996

89. Absence of ocular patches (CHRPE) in a family with familial adenomatous polyposis and mutation at codon 843 of the APC gene

Author: Scarcello, E, Deluca, M, Gismondi, V, Varesco, L, Carotighelli, C, Mosca, F, Cetta, F, Civitelli, S, Petracci, M, and Presciuttini, Silvano
Published: 1996

90. Absence of ocular patches (CHRPE) in a family with Familial Adenomatous Polyposis and mutation at codon 843 of the APC

Author: Scarcello, E., De Luca, M., Gismondi, V., Varesco, L., Caroti Ghelli, C., Mosca, F., Cetta, F., Civitelli, Serenella, Petracci, M., and Presciuttini, S.
Published: 1996

91. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis (vol 110, pg 1020, 1996)

Author: Vasen, H. F. A., Wijnen, J. T., Menko, F. H., Kleibeuker, J. H., Taal, B. G., Griffioen, G., Nagengast, F. M., Meijers-Heijboer, E. H., Bertario, L., Varesco, L., Bisgaard, M. L., Mohr, J., Fodde, R., Khan, P. M., and Other departments
Published: 1996

92. 7 NEW MUTATIONS IN HMSH2, AN HNPCC GENE, IDENTIFIED BY DENATURING GRADIENT-GEL ELECTROPHORESIS

Author: WIJNEN, J, VASEN, H, KHAN, PM, MENKO, FH, VANDERKLIFT, H, VANLEEUWEN, C, VANDENBROEK, M, VANLEEUWENCORNELISSE, [No Value], NAGENGAST, F, MEIJERSHEIJBOER, A, LINDHOUT, D, GRIFFIOEN, G, CATS, A, KLEIBEUKER, J, VARESCO, L, BERTARIO, L, BISGAARD, ML, MOHR, J, FODDE, R, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, POLYPOSIS, HOMOLOG, COLON-CANCER, INSTABILITY, nutritional and metabolic diseases, NONPOLYPOSIS COLORECTAL-CANCER, POLYMERASE CHAIN-REACTION, HEREDITARY, SINGLE-BASE CHANGES, digestive system diseases
Abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition. The recent isolation of the DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC has allowed the search for germ-line mutations in affected individuals. In this study we used denaturing gradient-gel electrophoresis to screen for mutations in the hMSH2 gene. Analysis of all the 16 exons of hMSH2, in 34 unrelated HNPCC kindreds, has revealed seven novel pathogenic germ-line mutations resulting in stop codons either directly or through frameshifts. Additionally, nucleotide substitutions giving rise to one missense, two silent, and one useful polymorphism have been identified. The proportion of families in which hMSH2 mutations were found is 21%. Although the spectrum of mutations spread at the hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able to establish any correlation between the site of the individual mutations and the corresponding tumor spectrum. Our results indicate that, given the genomic size and organization of the hMSH2 gene and the heterogeneity of its mutation spectrum, a rapid and efficient mutation detection procedure is necessary for routine molecular diagnosis and presymptomatic detection of the disease in a clinical setup.
Published: 1995

93. A low NM23.H1 gene expression identifyjng high malignancy human melanomas

Author: Caligo, Ma, Grammatico, P, Cipollini, G, Varesco, L, Del Porto, G, and Bevilacqua, Generoso
Published: 1994

94. A low NM23.H1 gene expression identifies human melanomas of higher malignancy

Author: Caligo, Ma, Grammatico, Paola, Cipollini, G, Varesco, L, DEL PORTO, Giuseppe, and Bevilacqua, G.
Subjects: NM23.H1 human melanomas
Published: 1994

95. Identification of APC gene mutations in Italian adenomatous polyposis coli patients by PCR-SSCP analysis

Author: Varesco, L, Gismondi, V, James, R, Robertson, M, Grammatico, Paola, Groden, J, Casarino, L, DE BENEDETTI, L, Bafico, A, Bertario, L, Sala, P, and Sassatelli, R.
Subjects: Adult, Genes, APC, Polymorphism, Genetic, Adolescent, Base Sequence, DNA Mutational Analysis, Molecular Sequence Data, DNA, Single-Stranded, Exons, Original Articles, Middle Aged, Polymerase Chain Reaction, APC, Adenomatous Polyposis Coli, Italy, Mutation, Humans, Nucleic Acid Conformation, Electrophoresis, Polyacrylamide Gel, Child, Frameshift Mutation, Sequence Deletion
Abstract: The APC gene is a putative human tumor-suppressor gene responsible for adenomatous polyposis coli (APC), an inherited, autosomal dominant predisposition to colon cancer. It is also implicated in the development of sporadic colorectal tumors. The characterization of APC gene mutations in APC patients is clinically important because DNA-based tests can be applied for presymptomatic diagnosis once a specific mutation has been identified in a family. Moreover, the identification of the spectrum of APC gene mutations in patients is of great interest in the study of the biological properties of the APC gene product. We analyzed the entire coding region of the APC gene by the PCR–single-strand conformation polymorphism method in 42 unrelated Italian APC patients. Mutations were found in 12 cases. These consist of small (5–14 bp) base-pair deletions leading to frameshifts; all are localized within exon 15. Two of these deletions, a 5-bp deletion at position 3183–3187 and a 5-bp deletion at position 3926–3930, are present in 3/42 and 7/42 cases of our series, respectively, indicating the presence of mutational hot spots at these two sites.
Published: 1993

96. Identification of APC gene mutations in Italian APC patients by PCR-SSCP analysis

Author: Varesco, L., Gismondi, V., James, R., Robertson, M., Grammatico, P., Groden, J., Casarino, L., De Benedetti, L., Bafico, A., Bertario, L., Sala, P., PONZ DE LEON, Maurizio, Sassatelli, R., Biasco, G., Allegretti, A., Aste, H., De Sanctis, S., Rossetti, C., Illeni, Mt, Sciarra, A., Del Porto, G., White, R., and Ferrara, Gb
Published: 1993

97. PP9 GERMLINE NONSYNONYMOUS VARIANT OF APC GENE IN A PATIENT WITH MULTIPLE COLORECTAL ADENOMAS

Author: Talenti, A., primary, Varesco, L., additional, Famiani, A., additional, Rossi, P., additional, Comito, D., additional, Ferraù, V., additional, Raffa, V., additional, and Romano, C., additional
Published: 2009
Full Text: View/download PDF

98. Prognostic significance of BRCA1, PARP1, and PARP2 in sporadic breast cancer

Author: Gennari, A., primary, Sormani, M., additional, Varesco, L., additional, Pronzato, P., additional, Viassolo, V., additional, Mirisola, V., additional, Pfeffer, U., additional, and Bruzzi, P., additional
Published: 2009
Full Text: View/download PDF

99. The NM23 gene maps to human chromosome band 17q22 and shows a restriction fragment length polymorphism with BglII

Author: Varesco, L, Caligo, Ma, Simi, P, Black, Dm, Nardini, V, Casarino, L, Rocchi, M, Ferrara, G, Solomon, E, and Bevilacqua, Generoso
Published: 1992

100. Recommendations for genetic counseling of familial adenomatous polyposis

Author: Guanti, G, Varesco, L, Crotti, N, Heouaine, A, De Stefano, F, Genuardi, Maurizio, Genuardi, M (ORCID:0000-0002-7410-8351), Guanti, G, Varesco, L, Crotti, N, Heouaine, A, De Stefano, F, Genuardi, Maurizio, and Genuardi, M (ORCID:0000-0002-7410-8351)
Abstract: NO ABSTRACT
Published: 1997

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