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J Natl Cancer Inst. 2011 Jan 19;103(2):105-16. doi: 10.1093/jnci/djq494. Epub 2010 Dec 17.

Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers.

Ramus SJ1, Kartsonaki C, Gayther SA, Pharoah PD, Sinilnikova OM, Beesley J, Chen X, McGuffog L, Healey S, Couch FJ, Wang X, Fredericksen Z, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Roversi G, Barile M, Viel A, Allavena A, Ottini L, Papi L, Gismondi V, Capra F, Radice P, Greene MH, Mai PL, Andrulis IL, Glendon G, Ozcelik H; OCGN, Thomassen M, Gerdes AM, Kruse TA, Cruger D, Jensen UB, Caligo MA, Olsson H, Kristoffersson U, Lindblom A, Arver B, Karlsson P, Stenmark Askmalm M, Borg A, Neuhausen SL, Ding YC, Nathanson KL, Domchek SM, Jakubowska A, Lubiński J, Huzarski T, Byrski T, Gronwald J, Górski B, Cybulski C, Dębniak T, Osorio A, Durán M, Tejada MI, Benítez J, Hamann U, Rookus MA, Verhoef S, Tilanus-Linthorst MA, Vreeswijk MP, Bodmer D, Ausems MG, van Os TA, Asperen CJ, Blok MJ, Meijers-Heijboer HE; HEBON; EMBRACE, Peock S, Cook M, Oliver C, Frost D, Dunning AM, Evans DG, Eeles R, Pichert G, Cole T, Hodgson S, Brewer C, Morrison PJ, Porteous M, Kennedy MJ, Rogers MT, Side LE, Donaldson A, Gregory H, Godwin A, Stoppa-Lyonnet D, Moncoutier V, Castera L, Mazoyer S, Barjhoux L, Bonadona V, Leroux D, Faivre L, Lidereau R, Nogues C, Bignon YJ, Prieur F, Collonge-Rame MA, Venat-Bouvet L, Fert-Ferrer S; GEMO Study Collaborators, Miron A, Buys SS, Hopper JL, Daly MB, John EM, Terry MB, Goldgar D; BCFR, Hansen Tv, Jønson L, Ejlertsen B, Agnarsson BA, Offit K, Kirchhoff T, Vijai J, Dutra-Clarke AV, Przybylo JA, Montagna M, Casella C, Imyanitov EN, Janavicius R, Blanco I, Lázaro C, Moysich KB, Karlan BY, Gross J, Beattie MS, Schmutzler R, Wappenschmidt B, Meindl A, Ruehl I, Fiebig B, Sutter C, Arnold N, Deissler H, Varon-Mateeva R, Kast K, Niederacher D, Gadzicki D, Caldes T, de la Hoya M, Nevanlinna H, Aittomäki K, Simard J, Soucy P; kConFab Investigators, Spurdle AB, Holland H, Chenevix-Trench G, Easton DF, Antoniou AC; Consortium of Investigators of Modifiers of BRCA1/2.

Collaborators (173)

Hogervorst FB, Verhoef S, Verheus M, van 't Veer LJ, van Leeuwen FE, Rookus MA, Collée M, van den Ouweland AM, Jager A, Hooning MJ, Tilanus-Linthorst MM, Seynaeve C, van Asperen CJ, Wijnen JT, Vreeswijk MP, Tollenaar RA, Devilee P, Ligtenberg MJ, Hoogerbrugge N, Ausems MG, van der Luijt RB, Aalfs CM, van Os TA, Gille JJ, Waisfisz Q, Meijers-Heijboer HE, Gomez-Garcia EB, van Roozendaal CE, Blok MJ, Oosterwijk JC, van der Hout AH, Mourits MJ, Vasen HF, Easton DF, Peock S, Cook M, Oliver C, Frost D, Gregory H, Miedzybrodzka Z, Morrison PJ, Jeffers L, Cole T, McKeown C, Ong KR, Boyes L, Donaldson A, Paterson J, Murray A, Rogers MT, McCann E, Kennedy MJ, Barton D, Porteous M, Brewer C, Kivuva E, Searle A, Goodman S, Davidson R, Murday V, Bradshaw N, Snadden L, Longmuir M, Watt C, Gibson S, Izatt L, Pichert G, Jacobs C, Langman C, Dorkins H, Barwell J, Chu C, Bishop T, Miller J, Ellis I, Houghton C, Evans DG, Lalloo F, Holt F, Side LE, Male A, Berlin C, Gardiner C, Douglas F, Claber O, Walker L, McLeod D, Halliday D, Durrell S, Stayner B, Eeles R, 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, Cook J, Quarrell O, Bardsley C, Robinson A, Hodgson S, Goff S, Brice G, Winchester L, Eccles D, Lucassen A, Crawford G, Tyler E, McBride D, Sinilnikova OM, Barjhoux L, Giraud S, Léone M, Mazoyer S, Stoppa-Lyonnet D, Gauthier-Villars M, Houdayer C, Moncoutier V, Belotti M, de Pauw A, Bressac-de-Paillerets B, Remenieras A, Byrde V, Caron O, Lenoir G, Bignon YJ, Uhrhammer N, Lasset C, Bonadona V, Hardouin A, Berthet P, Sobol H, Bourdon V, Noguchi T, Eisinger F, Coulet F, Colas C, Soubrier F, Coupier I, Peyrat JP, Fournier J, Révillion F, Vennin P, Adenis C, Rouleau E, Lidereau R, Demange L, Nogues C, Muller D, Fricker JP, Longy M, Sevenet N, Toulas C, Guimbaud R, Gladieff L, Feillel V, Leroux D, Dreyfus H, Rebischung C, Cassini C, Faivre L, Prieur F, Fert Ferrer S, Frénay M, Vénat-Bouvet L, Lynch HT.

Author information

1
Department of Gynaecological Oncology, UCL EGA Institute for Women's Health, University College London, London, UK. sramus@usc.edu

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.

PMID:
21169536
PMCID:
PMC3107565
DOI:
10.1093/jnci/djq494
[Indexed for MEDLINE]
Free PMC Article

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