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

Susan J. Ramus; Christiana Kartsonaki; Simon A. Gayther; Paul D.P. Pharoah; Olga M. Sinilnikova; Jonathan Beesley; Xiaoqing Chen; Lesley McGuffog; Sue Healey; Fergus J. Couch; Xianshu Wang; Zachary Fredericksen; Paolo Peterlongo; Siranoush Manoukian; Bernard Peissel; Daniela Zaffaroni; Gaia Roversi; Monica Barile; Alessandra Viel; Anna Allavena; Laura Ottini; Laura Papi; Viviana Gismondi; Fabio Capra; Paolo Radice; Mark H. Greene; Phuong L. Mai; Irene L. Andrulis; Gord Glendon; Hilmi Ozcelik; Mads Thomassen; Anne Marie Gerdes; Torben A. Kruse; Dorthe Cruger; Uffe Birk Jensen; Maria Adelaide Caligo; Hkan Olsson; Ulf Kristoffersson; Annika Lindblom; Brita Arver; Per Karlsson; Marie Stenmark Askmalm; Ake Borg; Susan L. Neuhausen; Yuan Chun Ding; Katherine L. Nathanson; Susan M. Domchek; Anna Jakubowska; Jan Lubiński; Tomasz Huzarski; Tomasz Byrski; Jacek Gronwald; Bohdan Górski; Cezary Cybulski; Tadeusz Dbniak; Ana Osorio; Mercedes Durán; Maria Isabel Tejada; Javier Benítez; Ute Hamann; Matti A. Rookus; Senno Verhoef; Madeleine A. Tilanus-Linthorst; Maaike P. Vreeswijk; Danielle Bodmer; Margreet G.E.M. Ausems; Theo A. Van Os; Christi J. Asperen; Marinus J. Blok; Hanne E.J. Meijers-Heijboer; Susan Peock; Margaret Cook; Clare Oliver; Debra Frost; Alison M. Dunning; D. Gareth Evans; Ros Eeles; Gabriella Pichert; Trevor Cole; Shirley Hodgson; Carole Brewer; Patrick J. Morrison; Mary Porteous; M. John Kennedy; Mark T. Rogers; Lucy E. Side; Alan Donaldson; Helen Gregory; Andrew Godwin; Dominique Stoppa-Lyonnet; Virginie Moncoutier; Laurent Castera; Sylvie Mazoyer; Laure Barjhoux; Valérie Bonadona; Dominique Leroux; Laurence Faivre; Rosette Lidereau; Catherine Nogues; Yves Jean Bignon; Fabienne Prieur; Marie Agns Collonge-Rame; Laurence Venat-Bouvet; Sandra Fert-Ferrer; Alex Miron; Saundra S. Buys; John L. Hopper; Mary B. Daly; Esther M. John; Mary Beth Terry; David Goldgar; Thomas V.O. Hansen; Lars Jønson; Bent Ejlertsen; Bjarni A. Agnarsson; Kenneth Offit; Tomas Kirchhoff; Joseph Vijai; Ana V.C. Dutra-Clarke; Jennifer A. Przybylo; Marco Montagna; Cinzia Casella; Evgeny N. Imyanitov; Ramunas Janavicius; Ignacio Blanco; Conxi Lázaro; Kirsten B. Moysich; Beth Y. Karlan; Jenny Gross; Mary S. Beattie; Rita Schmutzler; Barbara Wappenschmidt; Alfons Meindl; Ina Ruehl; Britta Fiebig; Christian Sutter; Norbert Arnold; Helmut Deissler; Raymonda Varon-Mateeva; Karin Kast; Dieter Niederacher; Dorothea Gadzicki; Trinidad Caldes; Miguel De La Hoya; Heli Nevanlinna; Kristiina Aittomäki; Jacques Simard; Penny Soucy; Amanda B. Spurdle; Helene Holland; Georgia Chenevix-Trench; Douglas F. Easton; Antonis C. Antoniou

doi:10.1093/jnci/djq494

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

Susan J. Ramus, Christiana Kartsonaki, Simon A. Gayther, Paul D.P. Pharoah, Olga M. Sinilnikova, Jonathan Beesley, Xiaoqing Chen, Lesley McGuffog, Sue Healey, Fergus J. Couch, Xianshu Wang, Zachary Fredericksen, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Gaia Roversi, Monica Barile, Alessandra Viel, Anna AllavenaLaura Ottini, Laura Papi, Viviana Gismondi, Fabio Capra, Paolo Radice, Mark H. Greene, Phuong L. Mai, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Mads Thomassen, Anne Marie Gerdes, Torben A. Kruse, Dorthe Cruger, Uffe Birk Jensen, Maria Adelaide Caligo, Hkan Olsson, Ulf Kristoffersson, Annika Lindblom, Brita Arver, Per Karlsson, Marie Stenmark Askmalm, Ake Borg, Susan L. Neuhausen, Yuan Chun Ding, Katherine L. Nathanson, Susan M. Domchek, Anna Jakubowska, Jan Lubiński, Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Bohdan Górski, Cezary Cybulski, Tadeusz Dbniak, Ana Osorio, Mercedes Durán, Maria Isabel Tejada, Javier Benítez, Ute Hamann, Matti A. Rookus, Senno Verhoef, Madeleine A. Tilanus-Linthorst, Maaike P. Vreeswijk, Danielle Bodmer, Margreet G.E.M. Ausems, Theo A. Van Os, Christi J. Asperen, Marinus J. Blok, Hanne E.J. Meijers-Heijboer, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Alison M. Dunning, D. Gareth Evans, Ros Eeles, Gabriella Pichert, Trevor Cole, Shirley Hodgson, Carole Brewer, Patrick J. Morrison, Mary Porteous, M. John Kennedy, Mark T. Rogers, Lucy E. Side, Alan Donaldson, Helen Gregory, Andrew Godwin, Dominique Stoppa-Lyonnet, Virginie Moncoutier, Laurent Castera, Sylvie Mazoyer, Laure Barjhoux, Valérie Bonadona, Dominique Leroux, Laurence Faivre, Rosette Lidereau, Catherine Nogues, Yves Jean Bignon, Fabienne Prieur, Marie Agns Collonge-Rame, Laurence Venat-Bouvet, Sandra Fert-Ferrer, Alex Miron, Saundra S. Buys, John L. Hopper, Mary B. Daly, Esther M. John, Mary Beth Terry, David Goldgar, Thomas V.O. Hansen, Lars Jønson, Bent Ejlertsen, Bjarni A. Agnarsson, Kenneth Offit, Tomas Kirchhoff, Joseph Vijai, Ana V.C. Dutra-Clarke, Jennifer A. Przybylo, Marco Montagna, Cinzia Casella, Evgeny N. Imyanitov, Ramunas Janavicius, Ignacio Blanco, Conxi Lázaro, Kirsten B. Moysich, Beth Y. Karlan, Jenny Gross, Mary S. Beattie, Rita Schmutzler, Barbara Wappenschmidt, Alfons Meindl, Ina Ruehl, Britta Fiebig, Christian Sutter, Norbert Arnold, Helmut Deissler, Raymonda Varon-Mateeva, Karin Kast, Dieter Niederacher, Dorothea Gadzicki, Trinidad Caldes, Miguel De La Hoya, Heli Nevanlinna, Kristiina Aittomäki, Jacques Simard, Penny Soucy, Amanda B. Spurdle, Helene Holland, Georgia Chenevix-Trench, Douglas F. Easton, Antonis C. Antoniou

Research output: Contribution to journal › Article › peer-review

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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. Method sWe genotyped rs3814113 in 10029 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.

Original language	English (US)
Pages (from-to)	105-116
Number of pages	12
Journal	Journal of the National Cancer Institute
Volume	103
Issue number	2
DOIs	https://doi.org/10.1093/jnci/djq494
State	Published - Jan 19 2011

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1093/jnci/djq494

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Ramus, S. J., Kartsonaki, C., Gayther, S. A., Pharoah, P. D. P., Sinilnikova, O. M., Beesley, J., Chen, X., McGuffog, L., Healey, S., Couch, F. J., Wang, X., Fredericksen, Z., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Roversi, G., Barile, M., Viel, A., ... Antoniou, A. C. (2011). Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Journal of the National Cancer Institute, 103(2), 105-116. https://doi.org/10.1093/jnci/djq494

Ramus, SJ, Kartsonaki, C, Gayther, SA, Pharoah, PDP, 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, 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, Dbniak, T, Osorio, A, Durán, M, Tejada, MI, Benítez, J, Hamann, U, Rookus, MA, Verhoef, S, Tilanus-Linthorst, MA, Vreeswijk, MP, Bodmer, D, Ausems, MGEM, Van Os, TA, Asperen, CJ, Blok, MJ, Meijers-Heijboer, HEJ, 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, Miron, A, Buys, SS, Hopper, JL, Daly, MB, John, EM, Terry, MB, Goldgar, D, Hansen, TVO, Jønson, L, Ejlertsen, B, Agnarsson, BA, Offit, K, Kirchhoff, T, Vijai, J, Dutra-Clarke, AVC, 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, Spurdle, AB, Holland, H, Chenevix-Trench, G, Easton, DF & Antoniou, AC 2011, 'Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers', Journal of the National Cancer Institute, vol. 103, no. 2, pp. 105-116. https://doi.org/10.1093/jnci/djq494

@article{7edf28832bab43809cc9ecd8ac3c9e55,

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

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. Method sWe genotyped rs3814113 in 10029 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 Christiana Kartsonaki and Gayther, {Simon A.} and Pharoah, {Paul D.P.} and Sinilnikova, {Olga M.} and Jonathan Beesley and Xiaoqing Chen and Lesley McGuffog and Sue Healey and Couch, {Fergus J.} and Xianshu Wang and Zachary Fredericksen and Paolo Peterlongo and Siranoush Manoukian and Bernard Peissel and Daniela Zaffaroni and Gaia Roversi and Monica Barile and Alessandra Viel and Anna Allavena and Laura Ottini and Laura Papi and Viviana Gismondi and Fabio Capra and Paolo Radice and Greene, {Mark H.} and Mai, {Phuong L.} and Andrulis, {Irene L.} and Gord Glendon and Hilmi Ozcelik and Mads Thomassen and Gerdes, {Anne Marie} and Kruse, {Torben A.} and Dorthe Cruger and Jensen, {Uffe Birk} and Caligo, {Maria Adelaide} and Hkan Olsson and Ulf Kristoffersson and Annika Lindblom and Brita Arver and Per Karlsson and {Stenmark Askmalm}, Marie and Ake Borg and Neuhausen, {Susan L.} and Ding, {Yuan Chun} and Nathanson, {Katherine L.} and Domchek, {Susan M.} and Anna Jakubowska and Jan Lubi{\'n}ski and Tomasz Huzarski and Tomasz Byrski and Jacek Gronwald and Bohdan G{\'o}rski and Cezary Cybulski and Tadeusz Dbniak and Ana Osorio and Mercedes Dur{\'a}n and Tejada, {Maria Isabel} and Javier Ben{\'i}tez and Ute Hamann and Rookus, {Matti A.} and Senno Verhoef and Tilanus-Linthorst, {Madeleine A.} and Vreeswijk, {Maaike P.} and Danielle Bodmer 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 Susan Peock and Margaret Cook and Clare Oliver and Debra Frost and Dunning, {Alison M.} and Evans, {D. Gareth} and Ros Eeles and Gabriella Pichert and Trevor Cole and Shirley Hodgson and Carole Brewer and Morrison, {Patrick J.} and Mary Porteous and Kennedy, {M. John} and Rogers, {Mark T.} and Side, {Lucy E.} and Alan Donaldson and Helen Gregory and Andrew Godwin and Dominique Stoppa-Lyonnet and Virginie Moncoutier and Laurent Castera and Sylvie Mazoyer and Laure Barjhoux and Val{\'e}rie Bonadona and Dominique Leroux and Laurence Faivre and Rosette Lidereau and Catherine Nogues and Bignon, {Yves Jean} and Fabienne Prieur and Collonge-Rame, {Marie Agns} and Laurence Venat-Bouvet and Sandra Fert-Ferrer and Alex Miron and Buys, {Saundra S.} and Hopper, {John L.} and Daly, {Mary B.} and John, {Esther M.} and Terry, {Mary Beth} and David Goldgar and Hansen, {Thomas V.O.} and Lars J{\o}nson and Bent Ejlertsen and Agnarsson, {Bjarni A.} and Kenneth Offit and Tomas Kirchhoff and Joseph Vijai and Dutra-Clarke, {Ana V.C.} and Przybylo, {Jennifer A.} and Marco Montagna and Cinzia Casella and Imyanitov, {Evgeny N.} and Ramunas Janavicius and Ignacio Blanco and Conxi L{\'a}zaro and Moysich, {Kirsten B.} and Karlan, {Beth Y.} and Jenny Gross and Beattie, {Mary S.} and Rita Schmutzler and Barbara Wappenschmidt and Alfons Meindl and Ina Ruehl and Britta Fiebig and Christian Sutter and Norbert Arnold and Helmut Deissler and Raymonda Varon-Mateeva and Karin Kast and Dieter Niederacher and Dorothea Gadzicki and Trinidad Caldes and {De La Hoya}, Miguel and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Jacques Simard and Penny Soucy and Spurdle, {Amanda B.} and Helene Holland and Georgia Chenevix-Trench and Easton, {Douglas F.} and Antoniou, {Antonis C.}",

year = "2011",

month = jan,

day = "19",

doi = "10.1093/jnci/djq494",

language = "English (US)",

volume = "103",

pages = "105--116",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

AU - Ramus, Susan J.

AU - Kartsonaki, Christiana

AU - Gayther, Simon A.

AU - Pharoah, Paul D.P.

AU - Sinilnikova, Olga M.

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Couch, Fergus J.

AU - Wang, Xianshu

AU - Fredericksen, Zachary

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Zaffaroni, Daniela

AU - Roversi, Gaia

AU - Barile, Monica

AU - Viel, Alessandra

AU - Allavena, Anna

AU - Ottini, Laura

AU - Papi, Laura

AU - Gismondi, Viviana

AU - Capra, Fabio

AU - Radice, Paolo

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Andrulis, Irene L.

AU - Glendon, Gord

AU - Ozcelik, Hilmi

AU - Thomassen, Mads

AU - Gerdes, Anne Marie

AU - Kruse, Torben A.

AU - Cruger, Dorthe

AU - Jensen, Uffe Birk

AU - Caligo, Maria Adelaide

AU - Olsson, Hkan

AU - Kristoffersson, Ulf

AU - Lindblom, Annika

AU - Arver, Brita

AU - Karlsson, Per

AU - Stenmark Askmalm, Marie

AU - Borg, Ake

AU - Neuhausen, Susan L.

AU - Ding, Yuan Chun

AU - Nathanson, Katherine L.

AU - Domchek, Susan M.

AU - Jakubowska, Anna

AU - Lubiński, Jan

AU - Huzarski, Tomasz

AU - Byrski, Tomasz

AU - Gronwald, Jacek

AU - Górski, Bohdan

AU - Cybulski, Cezary

AU - Dbniak, Tadeusz

AU - Osorio, Ana

AU - Durán, Mercedes

AU - Tejada, Maria Isabel

AU - Benítez, Javier

AU - Hamann, Ute

AU - Rookus, Matti A.

AU - Verhoef, Senno

AU - Tilanus-Linthorst, Madeleine A.

AU - Vreeswijk, Maaike P.

AU - Bodmer, Danielle

AU - Ausems, Margreet G.E.M.

AU - Van Os, Theo A.

AU - Asperen, Christi J.

AU - Blok, Marinus J.

AU - Meijers-Heijboer, Hanne E.J.

AU - Peock, Susan

AU - Cook, Margaret

AU - Oliver, Clare

AU - Frost, Debra

AU - Dunning, Alison M.

AU - Evans, D. Gareth

AU - Eeles, Ros

AU - Pichert, Gabriella

AU - Cole, Trevor

AU - Hodgson, Shirley

AU - Brewer, Carole

AU - Morrison, Patrick J.

AU - Porteous, Mary

AU - Kennedy, M. John

AU - Rogers, Mark T.

AU - Side, Lucy E.

AU - Donaldson, Alan

AU - Gregory, Helen

AU - Godwin, Andrew

AU - Stoppa-Lyonnet, Dominique

AU - Moncoutier, Virginie

AU - Castera, Laurent

AU - Mazoyer, Sylvie

AU - Barjhoux, Laure

AU - Bonadona, Valérie

AU - Leroux, Dominique

AU - Faivre, Laurence

AU - Lidereau, Rosette

AU - Nogues, Catherine

AU - Bignon, Yves Jean

AU - Prieur, Fabienne

AU - Collonge-Rame, Marie Agns

AU - Venat-Bouvet, Laurence

AU - Fert-Ferrer, Sandra

AU - Miron, Alex

AU - Buys, Saundra S.

AU - Hopper, John L.

AU - Daly, Mary B.

AU - John, Esther M.

AU - Terry, Mary Beth

AU - Goldgar, David

AU - Hansen, Thomas V.O.

AU - Jønson, Lars

AU - Ejlertsen, Bent

AU - Agnarsson, Bjarni A.

AU - Offit, Kenneth

AU - Kirchhoff, Tomas

AU - Vijai, Joseph

AU - Dutra-Clarke, Ana V.C.

AU - Przybylo, Jennifer A.

AU - Montagna, Marco

AU - Casella, Cinzia

AU - Imyanitov, Evgeny N.

AU - Janavicius, Ramunas

AU - Blanco, Ignacio

AU - Lázaro, Conxi

AU - Moysich, Kirsten B.

AU - Karlan, Beth Y.

AU - Gross, Jenny

AU - Beattie, Mary S.

AU - Schmutzler, Rita

AU - Wappenschmidt, Barbara

AU - Meindl, Alfons

AU - Ruehl, Ina

AU - Fiebig, Britta

AU - Sutter, Christian

AU - Arnold, Norbert

AU - Deissler, Helmut

AU - Varon-Mateeva, Raymonda

AU - Kast, Karin

AU - Niederacher, Dieter

AU - Gadzicki, Dorothea

AU - Caldes, Trinidad

AU - De La Hoya, Miguel

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Simard, Jacques

AU - Soucy, Penny

AU - Spurdle, Amanda B.

AU - Holland, Helene

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F.

AU - Antoniou, Antonis C.

PY - 2011/1/19

Y1 - 2011/1/19

N2 - 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. Method sWe genotyped rs3814113 in 10029 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.

AB - 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. Method sWe genotyped rs3814113 in 10029 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.

UR - http://www.scopus.com/inward/record.url?scp=79251507591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251507591&partnerID=8YFLogxK

U2 - 10.1093/jnci/djq494

DO - 10.1093/jnci/djq494

M3 - Article

C2 - 21169536

AN - SCOPUS:79251507591

SN - 0027-8874

VL - 103

SP - 105

EP - 116

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 2

ER -

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

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