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Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers.

Ramus, Susan J; Kartsonaki, Christiana; Gayther, Simon A; Pharoah, Paul D P; Sinilnikova, Olga M; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Healey, Sue and Couch, Fergus J, et al. (2011) In Journal of the National Cancer Institute 103.
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... (More)
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 × 10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 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. (Less)
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Journal of the National Cancer Institute
volume
103
publisher
Oxford University Press
external identifiers
  • WOS:000286472800008
  • PMID:21169536
  • Scopus:79251507591
ISSN
1460-2105
DOI
10.1093/jnci/djq494
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English
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yes
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e2340d2d-597d-4afb-aaf4-4e2bd5cacbfa (old id 1755995)
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http://www.ncbi.nlm.nih.gov/pubmed/21169536?dopt=Abstract
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2011-01-03 17:53:47
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2016-11-20 04:21:23
@misc{e2340d2d-597d-4afb-aaf4-4e2bd5cacbfa,
  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 × 10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 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.},
  author       = {Ramus, Susan J and Kartsonaki, Christiana and Gayther, Simon A and Pharoah, Paul D P and Sinilnikova, Olga M and Beesley, Jonathan and Chen, Xiaoqing and McGuffog, Lesley and Healey, Sue and Couch, Fergus J and Wang, Xianshu and Fredericksen, Zachary and Peterlongo, Paolo and Manoukian, Siranoush and Peissel, Bernard and Zaffaroni, Daniela and Roversi, Gaia and Barile, Monica and Viel, Alessandra and Allavena, Anna and Ottini, Laura and Papi, Laura and Gismondi, Viviana and Capra, Fabio and Radice, Paolo and Greene, Mark H and Mai, Phuong L and Andrulis, Irene L and Glendon, Gord and Ozcelik, Hilmi and Thomassen, Mads and Gerdes, Anne-Marie and Kruse, Torben A and Cruger, Dorthe and Jensen, Uffe Birk and Caligo, Maria Adelaide and Olsson, Håkan and Kristoffersson, Ulf and Lindblom, Annika and Arver, Brita and Karlsson, Per and Stenmark Askmalm, Marie and Borg, Åke and Neuhausen, Susan L and Ding, Yuan Chun and Nathanson, Katherine L and Domchek, Susan M and Jakubowska, Anna and Lubinski, Jan and Huzarski, Tomasz and Byrski, Tomasz and Gronwald, Jacek and Górski, Bohdan and Cybulski, Cezary and Debniak, Tadeusz and Osorio, Ana and Durán, Mercedes and Tejada, Maria-Isabel and Benítez, Javier and Hamann, Ute and Rookus, Matti A and Verhoef, Senno and Tilanus-Linthorst, Madeleine A and Vreeswijk, Maaike P and Bodmer, Danielle and Ausems, Margreet G E M and van Os, Theo A and Asperen, Christi J and Blok, Marinus J and Meijers-Heijboer, Hanne E J and Peock, Susan and Cook, Margaret and Oliver, Clare and Frost, Debra and Dunning, Alison M and Evans, D Gareth and Eeles, Ros and Pichert, Gabriella and Cole, Trevor and Hodgson, Shirley and Brewer, Carole and Morrison, Patrick J and Porteous, Mary and Kennedy, M John and Rogers, Mark T and Side, Lucy E and Donaldson, Alan and Gregory, Helen and Godwin, Andrew and Stoppa-Lyonnet, Dominique and Moncoutier, Virginie and Castera, Laurent and Mazoyer, Sylvie and Barjhoux, Laure and Bonadona, Valérie and Leroux, Dominique and Faivre, Laurence and Lidereau, Rosette and Nogues, Catherine and Bignon, Yves-Jean and Prieur, Fabienne and Collonge-Rame, Marie-Agnès and Venat-Bouvet, Laurence and Fert-Ferrer, Sandra and Miron, Alex and Buys, Saundra S and Hopper, John L and Daly, Mary B and John, Esther M and Terry, Mary Beth and Goldgar, David and Hansen, Thomas V O and Jønson, Lars and Ejlertsen, Bent and Agnarsson, Bjarni A and Offit, Kenneth and Kirchhoff, Tomas and Vijai, Joseph and Dutra-Clarke, Ana V C and Przybylo, Jennifer A and Montagna, Marco and Casella, Cinzia and Imyanitov, Evgeny N and Janavicius, Ramunas and Blanco, Ignacio and Lázaro, Conxi and Moysich, Kirsten B and Karlan, Beth Y and Gross, Jenny and Beattie, Mary S and Schmutzler, Rita and Wappenschmidt, Barbara and Meindl, Alfons and Ruehl, Ina and Fiebig, Britta and Sutter, Christian and Arnold, Norbert and Deissler, Helmut and Varon-Mateeva, Raymonda and Kast, Karin and Niederacher, Dieter and Gadzicki, Dorothea and Caldes, Trinidad and de la Hoya, Miguel and Nevanlinna, Heli and Aittomäki, Kristiina and Simard, Jacques and Soucy, Penny and Spurdle, Amanda B and Holland, Helene and Chenevix-Trench, Georgia and Easton, Douglas F and Antoniou, Antonis C},
  issn         = {1460-2105},
  language     = {eng},
  publisher    = {ARRAY(0xacc7248)},
  series       = {Journal of the National Cancer Institute},
  title        = {Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers.},
  url          = {http://dx.doi.org/10.1093/jnci/djq494},
  volume       = {103},
  year         = {2011},
}