Back to Search
Start Over
Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk
- Source :
- Plos Genetics, 9, 3, pp. e1003173, Plos Genetics, 9, e1003173, Gaudet, M M, Kuchenbaecker, K B, Vijai, J, Klein, R J, Kirchhoff, T, McGuffog, L, Barrowdale, D, Dunning, A M, Lee, A R, Dennis, J, Healey, S, Dicks, E, Soucy, P, Sinilnikova, O M, Pankratz, V S, Wang, X, Eldridge, R C, Tessier, D C, Vincent, D, Bacot, F, Hogervorst, F B L, Peock, S, Stoppa-Lyonnet, D, Peterlongo, P, Schmutzler, R K, Nathanson, K L, Piedmonte, M, Singer, C F, Thomassen, M, Hansen, T V O, Neuhausen, S L, Blanco, I, Greene, M H, Garber, J, Weitzel, J N, Andrulis, I L, Goldgar, D E, D'Andrea, E, Caldes, T, Nevanlinna, H, Osorio, A, van Rensburg, E J, Arason, A, Rennert, G, van den Ouweland, A M W, van der Hout, A H, Kets, C M, Aalfs, C M, Wijnen, J T, Ausems, M G E M & kConFab Investigators 2013, ' Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk ', P L o S Genetics, vol. 9, no. 3, e1003173 . https://doi.org/10.1371/journal.pgen.1003173, Dipòsit Digital de la UB, Universidad de Barcelona, Gaudet, M M, Kuchenbaecker, K B, Vijai, J, Klein, R J, Kirchhoff, T, McGuffog, L, Barrowdale, D, Dunning, A M, Lee, A R, Dennis, J, Healey, S, Dicks, E, Soucy, P, Sinilnikova, O M, Pankratz, V S, Wang, X, Eldridge, R C, Tessier, D C, Vincent, D, Bacot, F, Hogervorst, F B L, Peock, S, Stoppa-Lyonnet, D, Peterlongo, P, Schmutzler, R K, Nathanson, K L, Piedmonte, M, Singer, C F, Thomassen, M, Hansen, T V O, Neuhausen, S L, Blanco, I, Greene, M H, Garber, J, Weitzel, J N, Andrulis, I L, Goldgar, D E, D'Andrea, E, Caldes, T, Nevanlinna, H, Osorio, A, van Rensburg, E J, Arason, A, Rennert, G, van den Ouweland, A M W, van der Hout, A H, Kets, C M, Aalfs, C M, Wijnen, J T, Jensen, U B & KConFab Investigators 2013, ' Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk ', PLoS genetics, vol. 9, no. 3, pp. e1003173 . https://doi.org/10.1371/journal.pgen.1003173, Gaudet, M M, Kuchenbaecker, K B, Vijai, J, Klein, R J, Kirchhoff, T, McGuffog, L, Barrowdale, D, Dunning, A M, Lee, A, Dennis, J, Healey, S, Dicks, E, Soucy, P, Sinilnikova, O M, Pankratz, V S, Wang, X, Eldridge, R C, Tessier, D C, Vincent, D, Bacot, F, Hogervorst, F B L, Peock, S, Stoppa-Lyonnet, D, Coulet, F, Colas, C, Soubrier, F, Peterlongo, P, Schmutzler, R K, Nathanson, K L, Piedmonte, M, Singer, C F, Thomassen, M, Sokolowska, J, Bronner, M, Hansen, T V O, Neuhausen, S L, Blanco, I, Greene, M H, Garber, J, Weitzel, J N, Andrulis, I L, Goldgar, D E, D'Andrea, E, Caldes, T, Nevanlinna, H, Osorio, A, van Rensburg, E J, Arason, A, Rennert, G, van den Ouweland, A M W, van der Hout, A H, Kets, C M, Aalfs, C M, Wijnen, J T, Ausems, M G E M, Frost, D, Ellis, S, Fineberg, E, Platte, R, Evans, D G, Jacobs, C, Adlard, J, Tischkowitz, M, Porteous, M, Damiola, F, Golmard, L, Barjhoux, L, Longy, M, Belotti, M, Ferrer, S F, Mazoyer, S, Spurdle, A B, Manoukian, S, Barile, M, Genuardi, M, Arnold, N, Meindl, A, Sutter, C, Wappenschmidt, B, Domchek, S M, Pfeiler, G, Friedman, E, Jensen, U B, Robson, M, Shah, S, Lazaro, C, Mai, P L, Benitez, J, Southey, M C, Schmidt, M K, Fasching, P A, Peto, J, Humphreys, M K, Wang, Q, Michailidou, K, Sawyer, E J, Burwinkel, B, Guénel, P, Bojesen, S E, Milne, R L, Brenner, H, Lochmann, M, Brauch, H, Ko, Y D, Baisch, C, Fischer, H P, Bruening, T, Pesch, B, Rabstein, S, Spickenheuer, A, Aittomäki, K, Dörk, T, Margolin, S, Mannermaa, A, Lambrechts, D, Chang-Claude, J, Radice, P, Giles, G G, Haiman, C A, Winqvist, R, Devillee, P, García-Closas, M, Schoof, N, Hooning, M J, Cox, A, Pharoah, P D P, Jakubowska, A, Orr, N, González-Neira, A, Pita, G, Alonso, M R, Hall, P, Couch, F J, Simard, J, Altshuler, D, Easton, D F, Chenevix-Trench, G, Antoniou, A C, Offit, K, Rookus, M A, van Leeuwen, F E, Verhoef, S, de Lange, J L, Collée, J M, Seynaeve, C, van Deurzen, C H M, van Asperen, C J, Tollenaar, R A, Devilee, P, van Cronenburg, T C T E F, Mensenkamp, A R, van der Luijt, R B, van Os, T A M, Gille, J J P, Waisfisz, Q, Meijers-Heijboer, H E J, Gómez-Garcia, E B, Blok, M J, Oosterwijk, J C, Mourits, M J, de Bock, G H, Vasen, H F, Miedzybrodzka, Z, Gregory, H, Morrison, P, Jeffers, L, Cole, T, Ong, K R, Hoffman, J, Donaldson, A, James, M, Paterson, J, 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, Davidson, R, Murday, V, Bradshaw, N, Snadden, L, Longmuir, M, Watt, C, Gibson, S, Haque, E, Tobias, E, Duncan, A, Izatt, L, Langman, C, Brady, A, Dorkins, H, Melville, A, Randhawa, K, Barwell, J, Serra-Feliu, G, Ellis, I, Houghton, C, Lalloo, F, Taylor, J, Side, L, Male, A, Berlin, C, Eason, J, Douglas, F, Claber, O, Collier, R, Jobson, I, Walker, L, McLeod, D, Durell, S, Stayner, B, Eeles, R A, Shanley, S, Rahman, N, Houlston, R, Bancroft, E, Page, E, Ardern-Jones, A, Kohut, K, Wiggins, J, Castro, E, Killick, E, Martin, S, Rea, G, Kulkarni, A, Cook, J, Quarrell, O, Bardsley, C, Hodgson, S, 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, Verny-Pierre, C, Giraud, S, Léone, M, Gauthier-Villars, M, Buecher, B, Houdayer, C, Moncoutier, V, Tirapo, C, de Pauw, A, Bressac-de-Paillerets, B, Caron, O, Bignon, Y J, Uhrhammer, N, Lasset, C, Bonadona, V, Handallou, S, Hardouin, A, Berthet, P, Sobol, H, Bourdon, V, Noguchi, T, Remenieras, A, Coupier, I, Pujol, P, Peyrat, J P, Fournier, J, Révillion, F, Vennin, P, Adenis, C, Rouleau, E, Lidereau, R, Demange, L, Nogues, C, Muller, D, Fricker, J P, Barouk-Simonet, E, Bonnet, F, Bubien, V, Sevenet, N, Toulas, C, Guimbaud, R, Gladieff, L, Feillel, V, Dreyfus, H, Rebischung, C, Peysselon, M, Coron, F, Faivre, L, Prieur, F, Lebrun, M, Kientz, C, Frénay, M, Vénat-Bouvet, L, Delnatte, C, Mortemousque, I, Lynch, H T, Snyder, C L, EMBRACE, HEBON, GENICA Network, GEMO Study, KConFab Investigators & Ontario Cancer Genetics Network 2013, ' Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk ', PLoS Genetics, vol. 9, no. 3, e1003173 . https://doi.org/10.1371/journal.pgen.1003173, PLoS Genetics; Vol 9, PLoS Genetics, 9(3), Recercat. Dipósit de la Recerca de Catalunya, instname, PLoS Genetics (print), 9(3). Public Library of Science, PLoS Genetics, PLoS genetics, 9(3). Public Library of Science, PLoS Genetics, 9(3):e1003173. Public Library of Science, PLoS genetics, 9(3). PUBLIC LIBRARY SCIENCE, PLoS Genetics, Vol 9, Iss 3, p e1003173 (2013)
- Publication Year :
- 2013
-
Abstract
- Contains fulltext : 118578.pdf (Publisher’s version ) (Open Access) Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9x10(-8)). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer.
- Subjects :
- Cancer Research
SUSCEPTIBILITY ALLELES
Genome-wide association study
Aetiology, screening and detection [ONCOL 5]
QH426-470
Settore MED/03 - GENETICA MEDICA
Genoma humà
SUBTYPES
Breast cancer
0302 clinical medicine
Risk Factors
CDKN2A
Genotype
BRCA2 MUTATION CARRIERS
Malalties hereditàries
GWAS
skin and connective tissue diseases
Genetics (clinical)
POPULATION
2. Zero hunger
Genetics
0303 health sciences
education.field_of_study
BRCA1 Protein
COMMON VARIANTS
genetic modifiers
BRCA2
cancer risk
Middle Aged
3. Good health
030220 oncology & carcinogenesis
Chromosomes, Human, Pair 6
Female
Genetic diseases
Adult
Heterozygote
Medizinische Fakultät -ohne weitere Spezifikation
education
Population
Breast Neoplasms
Single-nucleotide polymorphism
Locus (genetics)
Human chromosomes
Biology
Polymorphism, Single Nucleotide
OVARIAN-CANCER
BRCA2-specific modifier locus at 6p24
Càncer de mama
03 medical and health sciences
TRANSCRIPTION FACTOR AP-2
SDG 3 - Good Health and Well-being
medicine
Humans
Genetic Predisposition to Disease
ddc:610
Allele
GENOME-WIDE ASSOCIATION
Molecular Biology
Alleles
Ecology, Evolution, Behavior and Systematics
Aged
030304 developmental biology
BRCA2 Protein
Cromosomes humans
Human genome
Hereditary cancer and cancer-related syndromes [ONCOL 1]
CONSORTIUM
medicine.disease
Mutation
3111 Biomedicine
ZNF365
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15537390 and 15537404
- Database :
- OpenAIRE
- Journal :
- Plos Genetics, 9, 3, pp. e1003173, Plos Genetics, 9, e1003173, Gaudet, M M, Kuchenbaecker, K B, Vijai, J, Klein, R J, Kirchhoff, T, McGuffog, L, Barrowdale, D, Dunning, A M, Lee, A R, Dennis, J, Healey, S, Dicks, E, Soucy, P, Sinilnikova, O M, Pankratz, V S, Wang, X, Eldridge, R C, Tessier, D C, Vincent, D, Bacot, F, Hogervorst, F B L, Peock, S, Stoppa-Lyonnet, D, Peterlongo, P, Schmutzler, R K, Nathanson, K L, Piedmonte, M, Singer, C F, Thomassen, M, Hansen, T V O, Neuhausen, S L, Blanco, I, Greene, M H, Garber, J, Weitzel, J N, Andrulis, I L, Goldgar, D E, D'Andrea, E, Caldes, T, Nevanlinna, H, Osorio, A, van Rensburg, E J, Arason, A, Rennert, G, van den Ouweland, A M W, van der Hout, A H, Kets, C M, Aalfs, C M, Wijnen, J T, Ausems, M G E M & kConFab Investigators 2013, ' Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk ', P L o S Genetics, vol. 9, no. 3, e1003173 . https://doi.org/10.1371/journal.pgen.1003173, Dipòsit Digital de la UB, Universidad de Barcelona, Gaudet, M M, Kuchenbaecker, K B, Vijai, J, Klein, R J, Kirchhoff, T, McGuffog, L, Barrowdale, D, Dunning, A M, Lee, A R, Dennis, J, Healey, S, Dicks, E, Soucy, P, Sinilnikova, O M, Pankratz, V S, Wang, X, Eldridge, R C, Tessier, D C, Vincent, D, Bacot, F, Hogervorst, F B L, Peock, S, Stoppa-Lyonnet, D, Peterlongo, P, Schmutzler, R K, Nathanson, K L, Piedmonte, M, Singer, C F, Thomassen, M, Hansen, T V O, Neuhausen, S L, Blanco, I, Greene, M H, Garber, J, Weitzel, J N, Andrulis, I L, Goldgar, D E, D'Andrea, E, Caldes, T, Nevanlinna, H, Osorio, A, van Rensburg, E J, Arason, A, Rennert, G, van den Ouweland, A M W, van der Hout, A H, Kets, C M, Aalfs, C M, Wijnen, J T, Jensen, U B & KConFab Investigators 2013, ' Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk ', PLoS genetics, vol. 9, no. 3, pp. e1003173 . https://doi.org/10.1371/journal.pgen.1003173, Gaudet, M M, Kuchenbaecker, K B, Vijai, J, Klein, R J, Kirchhoff, T, McGuffog, L, Barrowdale, D, Dunning, A M, Lee, A, Dennis, J, Healey, S, Dicks, E, Soucy, P, Sinilnikova, O M, Pankratz, V S, Wang, X, Eldridge, R C, Tessier, D C, Vincent, D, Bacot, F, Hogervorst, F B L, Peock, S, Stoppa-Lyonnet, D, Coulet, F, Colas, C, Soubrier, F, Peterlongo, P, Schmutzler, R K, Nathanson, K L, Piedmonte, M, Singer, C F, Thomassen, M, Sokolowska, J, Bronner, M, Hansen, T V O, Neuhausen, S L, Blanco, I, Greene, M H, Garber, J, Weitzel, J N, Andrulis, I L, Goldgar, D E, D'Andrea, E, Caldes, T, Nevanlinna, H, Osorio, A, van Rensburg, E J, Arason, A, Rennert, G, van den Ouweland, A M W, van der Hout, A H, Kets, C M, Aalfs, C M, Wijnen, J T, Ausems, M G E M, Frost, D, Ellis, S, Fineberg, E, Platte, R, Evans, D G, Jacobs, C, Adlard, J, Tischkowitz, M, Porteous, M, Damiola, F, Golmard, L, Barjhoux, L, Longy, M, Belotti, M, Ferrer, S F, Mazoyer, S, Spurdle, A B, Manoukian, S, Barile, M, Genuardi, M, Arnold, N, Meindl, A, Sutter, C, Wappenschmidt, B, Domchek, S M, Pfeiler, G, Friedman, E, Jensen, U B, Robson, M, Shah, S, Lazaro, C, Mai, P L, Benitez, J, Southey, M C, Schmidt, M K, Fasching, P A, Peto, J, Humphreys, M K, Wang, Q, Michailidou, K, Sawyer, E J, Burwinkel, B, Guénel, P, Bojesen, S E, Milne, R L, Brenner, H, Lochmann, M, Brauch, H, Ko, Y D, Baisch, C, Fischer, H P, Bruening, T, Pesch, B, Rabstein, S, Spickenheuer, A, Aittomäki, K, Dörk, T, Margolin, S, Mannermaa, A, Lambrechts, D, Chang-Claude, J, Radice, P, Giles, G G, Haiman, C A, Winqvist, R, Devillee, P, García-Closas, M, Schoof, N, Hooning, M J, Cox, A, Pharoah, P D P, Jakubowska, A, Orr, N, González-Neira, A, Pita, G, Alonso, M R, Hall, P, Couch, F J, Simard, J, Altshuler, D, Easton, D F, Chenevix-Trench, G, Antoniou, A C, Offit, K, Rookus, M A, van Leeuwen, F E, Verhoef, S, de Lange, J L, Collée, J M, Seynaeve, C, van Deurzen, C H M, van Asperen, C J, Tollenaar, R A, Devilee, P, van Cronenburg, T C T E F, Mensenkamp, A R, van der Luijt, R B, van Os, T A M, Gille, J J P, Waisfisz, Q, Meijers-Heijboer, H E J, Gómez-Garcia, E B, Blok, M J, Oosterwijk, J C, Mourits, M J, de Bock, G H, Vasen, H F, Miedzybrodzka, Z, Gregory, H, Morrison, P, Jeffers, L, Cole, T, Ong, K R, Hoffman, J, Donaldson, A, James, M, Paterson, J, 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, Davidson, R, Murday, V, Bradshaw, N, Snadden, L, Longmuir, M, Watt, C, Gibson, S, Haque, E, Tobias, E, Duncan, A, Izatt, L, Langman, C, Brady, A, Dorkins, H, Melville, A, Randhawa, K, Barwell, J, Serra-Feliu, G, Ellis, I, Houghton, C, Lalloo, F, Taylor, J, Side, L, Male, A, Berlin, C, Eason, J, Douglas, F, Claber, O, Collier, R, Jobson, I, Walker, L, McLeod, D, Durell, S, Stayner, B, Eeles, R A, Shanley, S, Rahman, N, Houlston, R, Bancroft, E, Page, E, Ardern-Jones, A, Kohut, K, Wiggins, J, Castro, E, Killick, E, Martin, S, Rea, G, Kulkarni, A, Cook, J, Quarrell, O, Bardsley, C, Hodgson, S, 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, Verny-Pierre, C, Giraud, S, Léone, M, Gauthier-Villars, M, Buecher, B, Houdayer, C, Moncoutier, V, Tirapo, C, de Pauw, A, Bressac-de-Paillerets, B, Caron, O, Bignon, Y J, Uhrhammer, N, Lasset, C, Bonadona, V, Handallou, S, Hardouin, A, Berthet, P, Sobol, H, Bourdon, V, Noguchi, T, Remenieras, A, Coupier, I, Pujol, P, Peyrat, J P, Fournier, J, Révillion, F, Vennin, P, Adenis, C, Rouleau, E, Lidereau, R, Demange, L, Nogues, C, Muller, D, Fricker, J P, Barouk-Simonet, E, Bonnet, F, Bubien, V, Sevenet, N, Toulas, C, Guimbaud, R, Gladieff, L, Feillel, V, Dreyfus, H, Rebischung, C, Peysselon, M, Coron, F, Faivre, L, Prieur, F, Lebrun, M, Kientz, C, Frénay, M, Vénat-Bouvet, L, Delnatte, C, Mortemousque, I, Lynch, H T, Snyder, C L, EMBRACE, HEBON, GENICA Network, GEMO Study, KConFab Investigators & Ontario Cancer Genetics Network 2013, ' Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk ', PLoS Genetics, vol. 9, no. 3, e1003173 . https://doi.org/10.1371/journal.pgen.1003173, PLoS Genetics; Vol 9, PLoS Genetics, 9(3), Recercat. Dipósit de la Recerca de Catalunya, instname, PLoS Genetics (print), 9(3). Public Library of Science, PLoS Genetics, PLoS genetics, 9(3). Public Library of Science, PLoS Genetics, 9(3):e1003173. Public Library of Science, PLoS genetics, 9(3). PUBLIC LIBRARY SCIENCE, PLoS Genetics, Vol 9, Iss 3, p e1003173 (2013)
- Accession number :
- edsair.doi.dedup.....be8bbb324fd27ffcb52b62a1a013638c