Ramus, SJ and Kartsonaki, C and Gayther, SA and Pharoah, PDP and Sinilnikova, OM and Beesley, J and Chen, XQ and McGuffog, L and Healey, S and Couch, FJ and Wang, XS and Fredericksen, Z and Peterlongo, P and Manoukian, S and Peissel, B and Zaffaroni, D and Roversi, G and Barile, M and Viel, A and Allavena, A and Ottini, L and Papi, L and Gismondi, V and Capra, F and Radice, P and Greene, MH and Mai, PL and Andrulis, IL and Glendon, G and Ozcelik, H and Thomassen, M and Gerdes, AM and Kruse, TA and Cruger, D and Jensen, UB and Caligo, MA and Olsson, H and Kristoffersson, U and Lindblom, A and Arver, B and Karlsson, P and Askmalm, MS and Borg, A and Neuhausen, SL and Ding, YC and Nathanson, KL and Domchek, SM and Jakubowska, A and Lubinski, J and Huzarski, T and Byrski, T and Gronwald, J and Gorski, B and Cybulski, C and Debniak, T and Osorio, A and Duran, M and Tejada, MI and Benitez, J and Hamann, U and Rookus, MA and Verhoef, S and Tilanus-Linthorst, MA and Vreeswijk, MP and Bodmer, D and Ausems, MGEM and van Os, TA and Asperen, CJ and Blok, MJ and Meijers-Heijboer, HEJ and Peock, S and Cook, M and Oliver, C and Frost, D and Dunning, AM and Evans, DG and Eeles, R and Pichert, G and Cole, T and Hodgson, S and Brewer, C and Morrison, PJ and Porteous, M and Kennedy, MJ and Rogers, MT and Side, LE and Donaldson, A and Gregory, H and Godwin, A and Stoppa-Lyonnet, D and Moncoutier, V and Castera, L and Mazoyer, S and Barjhoux, L and Bonadona, V and Leroux, D and Faivre, L and Lidereau, R and Nogues, C and Bignon, YJ and Prieur, F and Collonge-Rame, MA and Venat-Bouvet, L and Fert-Ferrer, S and Miron, A and Buys, SS and Hopper, JL and Daly, MB and John, EM and Terry, MB and Goldgar, D and Hansen, TVO and Jonson, L and Ejlertsen, B and Agnarsson, BA and Offit, K and Kirchhoff, T and Vijai, J and Dutra-Clarke, AVC and Przybylo, JA and Montagna, M and Casella, C and Imyanitov, EN and Janavicius, R and Blanco, I and Lazaro, C and Moysich, KB and Karlan, BY and Gross, J and Beattie, MS and Schmutzler, R and Wappenschmidt, B and Meindl, A and Ruehl, I and Fiebig, B and Sutter, C and Arnold, N and Deissler, H and Varon-Mateeva, R and Kast, K and Niederacher, D and Gadzicki, D and Caldes, T and de la Hoya, M and Nevanlinna, H and Aittomaki, K and Simard, J and Soucy, P and Spurdle, AB and Holland, H and Chenevix-Trench, G and Easton, DF and Antoniou, AC and OCGN, and HEBON, and EMBRACE, and GEMO Study Collaborators, and BCFR, and KConFab Investigators, and Consortium Investigators Modifiers, (2011) Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers. J NATL CANCER I , 103 (2) ? - ?. 10.1093/jnci/djq494.
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Abstract
Background Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2.Methods We genotyped rs3814113 in 10 029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided.Results The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 x 10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 x 10(-4)). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%.Conclusion Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation.
| Type: | Article |
|---|---|
| Title: | Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers |
| DOI: | 10.1093/jnci/djq494 |
| Keywords: | GENOME-WIDE ASSOCIATION, BREAST-CANCER, SUSCEPTIBILITY LOCI, GERMLINE MUTATIONS, ALLELES, IDENTIFICATION, BASONUCLIN-2, POPULATION, PROTEINS, FAMILIES |
| UCL classification: | UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Women's Health > Women's Cancer |
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