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

Identifieur interne : 006147 ( Main/Exploration ); précédent : 006146; suivant : 006148

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

Auteurs : 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 ; H Kan 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 Lubi Ski ; Tomasz Huzarski ; Tomasz Byrski ; Jacek Gronwald ; Bohdan G Rski ; Cezary Cybulski ; Tadeusz D Bniak ; 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-Agnès 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 J Nson ; 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 Aittom Ki ; Jacques Simard ; Penny Soucy ; Amanda B. Spurdle ; Helene Holland ; Georgia Chenevix-Trench ; Douglas F. Easton ; Antonis C. Antoniou

Source :

RBID : PMC:3107565

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.


Url:
DOI: 10.1093/jnci/djq494
PubMed: 21169536
PubMed Central: 3107565


Affiliations:


Links toward previous steps (curation, corpus...)


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<name sortKey="Nogues, Catherine" sort="Nogues, Catherine" uniqKey="Nogues C" first="Catherine" last="Nogues">Catherine Nogues</name>
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<name sortKey="Bignon, Yves Jean" sort="Bignon, Yves Jean" uniqKey="Bignon Y" first="Yves-Jean" last="Bignon">Yves-Jean Bignon</name>
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<name sortKey="Collonge Rame, Marie Agnes" sort="Collonge Rame, Marie Agnes" uniqKey="Collonge Rame M" first="Marie-Agnès" last="Collonge-Rame">Marie-Agnès Collonge-Rame</name>
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<name sortKey="Venat Bouvet, Laurence" sort="Venat Bouvet, Laurence" uniqKey="Venat Bouvet L" first="Laurence" last="Venat-Bouvet">Laurence Venat-Bouvet</name>
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<name sortKey="Agnarsson, Bjarni A" sort="Agnarsson, Bjarni A" uniqKey="Agnarsson B" first="Bjarni A." last="Agnarsson">Bjarni A. Agnarsson</name>
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</author>
<author>
<name sortKey="Cook, Margaret" sort="Cook, Margaret" uniqKey="Cook M" first="Margaret" last="Cook">Margaret Cook</name>
</author>
<author>
<name sortKey="Oliver, Clare" sort="Oliver, Clare" uniqKey="Oliver C" first="Clare" last="Oliver">Clare Oliver</name>
</author>
<author>
<name sortKey="Frost, Debra" sort="Frost, Debra" uniqKey="Frost D" first="Debra" last="Frost">Debra Frost</name>
</author>
<author>
<name sortKey="Dunning, Alison M" sort="Dunning, Alison M" uniqKey="Dunning A" first="Alison M." last="Dunning">Alison M. Dunning</name>
</author>
<author>
<name sortKey="Evans, D Gareth" sort="Evans, D Gareth" uniqKey="Evans D" first="D. Gareth" last="Evans">D. Gareth Evans</name>
</author>
<author>
<name sortKey="Eeles, Ros" sort="Eeles, Ros" uniqKey="Eeles R" first="Ros" last="Eeles">Ros Eeles</name>
</author>
<author>
<name sortKey="Pichert, Gabriella" sort="Pichert, Gabriella" uniqKey="Pichert G" first="Gabriella" last="Pichert">Gabriella Pichert</name>
</author>
<author>
<name sortKey="Cole, Trevor" sort="Cole, Trevor" uniqKey="Cole T" first="Trevor" last="Cole">Trevor Cole</name>
</author>
<author>
<name sortKey="Hodgson, Shirley" sort="Hodgson, Shirley" uniqKey="Hodgson S" first="Shirley" last="Hodgson">Shirley Hodgson</name>
</author>
<author>
<name sortKey="Brewer, Carole" sort="Brewer, Carole" uniqKey="Brewer C" first="Carole" last="Brewer">Carole Brewer</name>
</author>
<author>
<name sortKey="Morrison, Patrick J" sort="Morrison, Patrick J" uniqKey="Morrison P" first="Patrick J." last="Morrison">Patrick J. Morrison</name>
</author>
<author>
<name sortKey="Porteous, Mary" sort="Porteous, Mary" uniqKey="Porteous M" first="Mary" last="Porteous">Mary Porteous</name>
</author>
<author>
<name sortKey="Kennedy, M John" sort="Kennedy, M John" uniqKey="Kennedy M" first="M. John" last="Kennedy">M. John Kennedy</name>
</author>
<author>
<name sortKey="Rogers, Mark T" sort="Rogers, Mark T" uniqKey="Rogers M" first="Mark T." last="Rogers">Mark T. Rogers</name>
</author>
<author>
<name sortKey="Side, Lucy E" sort="Side, Lucy E" uniqKey="Side L" first="Lucy E." last="Side">Lucy E. Side</name>
</author>
<author>
<name sortKey="Donaldson, Alan" sort="Donaldson, Alan" uniqKey="Donaldson A" first="Alan" last="Donaldson">Alan Donaldson</name>
</author>
<author>
<name sortKey="Gregory, Helen" sort="Gregory, Helen" uniqKey="Gregory H" first="Helen" last="Gregory">Helen Gregory</name>
</author>
<author>
<name sortKey="Godwin, Andrew" sort="Godwin, Andrew" uniqKey="Godwin A" first="Andrew" last="Godwin">Andrew Godwin</name>
</author>
<author>
<name sortKey="Stoppa Lyonnet, Dominique" sort="Stoppa Lyonnet, Dominique" uniqKey="Stoppa Lyonnet D" first="Dominique" last="Stoppa-Lyonnet">Dominique Stoppa-Lyonnet</name>
</author>
<author>
<name sortKey="Moncoutier, Virginie" sort="Moncoutier, Virginie" uniqKey="Moncoutier V" first="Virginie" last="Moncoutier">Virginie Moncoutier</name>
</author>
<author>
<name sortKey="Castera, Laurent" sort="Castera, Laurent" uniqKey="Castera L" first="Laurent" last="Castera">Laurent Castera</name>
</author>
<author>
<name sortKey="Mazoyer, Sylvie" sort="Mazoyer, Sylvie" uniqKey="Mazoyer S" first="Sylvie" last="Mazoyer">Sylvie Mazoyer</name>
</author>
<author>
<name sortKey="Barjhoux, Laure" sort="Barjhoux, Laure" uniqKey="Barjhoux L" first="Laure" last="Barjhoux">Laure Barjhoux</name>
</author>
<author>
<name sortKey="Bonadona, Valerie" sort="Bonadona, Valerie" uniqKey="Bonadona V" first="Valérie" last="Bonadona">Valérie Bonadona</name>
</author>
<author>
<name sortKey="Leroux, Dominique" sort="Leroux, Dominique" uniqKey="Leroux D" first="Dominique" last="Leroux">Dominique Leroux</name>
</author>
<author>
<name sortKey="Faivre, Laurence" sort="Faivre, Laurence" uniqKey="Faivre L" first="Laurence" last="Faivre">Laurence Faivre</name>
</author>
<author>
<name sortKey="Lidereau, Rosette" sort="Lidereau, Rosette" uniqKey="Lidereau R" first="Rosette" last="Lidereau">Rosette Lidereau</name>
</author>
<author>
<name sortKey="Nogues, Catherine" sort="Nogues, Catherine" uniqKey="Nogues C" first="Catherine" last="Nogues">Catherine Nogues</name>
</author>
<author>
<name sortKey="Bignon, Yves Jean" sort="Bignon, Yves Jean" uniqKey="Bignon Y" first="Yves-Jean" last="Bignon">Yves-Jean Bignon</name>
</author>
<author>
<name sortKey="Prieur, Fabienne" sort="Prieur, Fabienne" uniqKey="Prieur F" first="Fabienne" last="Prieur">Fabienne Prieur</name>
</author>
<author>
<name sortKey="Collonge Rame, Marie Agnes" sort="Collonge Rame, Marie Agnes" uniqKey="Collonge Rame M" first="Marie-Agnès" last="Collonge-Rame">Marie-Agnès Collonge-Rame</name>
</author>
<author>
<name sortKey="Venat Bouvet, Laurence" sort="Venat Bouvet, Laurence" uniqKey="Venat Bouvet L" first="Laurence" last="Venat-Bouvet">Laurence Venat-Bouvet</name>
</author>
<author>
<name sortKey="Fert Ferrer, Sandra" sort="Fert Ferrer, Sandra" uniqKey="Fert Ferrer S" first="Sandra" last="Fert-Ferrer">Sandra Fert-Ferrer</name>
</author>
<author>
<name sortKey="Miron, Alex" sort="Miron, Alex" uniqKey="Miron A" first="Alex" last="Miron">Alex Miron</name>
</author>
<author>
<name sortKey="Buys, Saundra S" sort="Buys, Saundra S" uniqKey="Buys S" first="Saundra S." last="Buys">Saundra S. Buys</name>
</author>
<author>
<name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name>
</author>
<author>
<name sortKey="Daly, Mary B" sort="Daly, Mary B" uniqKey="Daly M" first="Mary B." last="Daly">Mary B. Daly</name>
</author>
<author>
<name sortKey="John, Esther M" sort="John, Esther M" uniqKey="John E" first="Esther M." last="John">Esther M. John</name>
</author>
<author>
<name sortKey="Terry, Mary Beth" sort="Terry, Mary Beth" uniqKey="Terry M" first="Mary Beth" last="Terry">Mary Beth Terry</name>
</author>
<author>
<name sortKey="Goldgar, David" sort="Goldgar, David" uniqKey="Goldgar D" first="David" last="Goldgar">David Goldgar</name>
</author>
<author>
<name sortKey="Hansen, Thomas V O" sort="Hansen, Thomas V O" uniqKey="Hansen T" first="Thomas V. O." last="Hansen">Thomas V. O. Hansen</name>
</author>
<author>
<name sortKey="J Nson, Lars" sort="J Nson, Lars" uniqKey="J Nson L" first="Lars" last="J Nson">Lars J Nson</name>
</author>
<author>
<name sortKey="Ejlertsen, Bent" sort="Ejlertsen, Bent" uniqKey="Ejlertsen B" first="Bent" last="Ejlertsen">Bent Ejlertsen</name>
</author>
<author>
<name sortKey="Agnarsson, Bjarni A" sort="Agnarsson, Bjarni A" uniqKey="Agnarsson B" first="Bjarni A." last="Agnarsson">Bjarni A. Agnarsson</name>
</author>
<author>
<name sortKey="Offit, Kenneth" sort="Offit, Kenneth" uniqKey="Offit K" first="Kenneth" last="Offit">Kenneth Offit</name>
</author>
<author>
<name sortKey="Kirchhoff, Tomas" sort="Kirchhoff, Tomas" uniqKey="Kirchhoff T" first="Tomas" last="Kirchhoff">Tomas Kirchhoff</name>
</author>
<author>
<name sortKey="Vijai, Joseph" sort="Vijai, Joseph" uniqKey="Vijai J" first="Joseph" last="Vijai">Joseph Vijai</name>
</author>
<author>
<name sortKey="Dutra Clarke, Ana V C" sort="Dutra Clarke, Ana V C" uniqKey="Dutra Clarke A" first="Ana V. C." last="Dutra-Clarke">Ana V. C. Dutra-Clarke</name>
</author>
<author>
<name sortKey="Przybylo, Jennifer A" sort="Przybylo, Jennifer A" uniqKey="Przybylo J" first="Jennifer A." last="Przybylo">Jennifer A. Przybylo</name>
</author>
<author>
<name sortKey="Montagna, Marco" sort="Montagna, Marco" uniqKey="Montagna M" first="Marco" last="Montagna">Marco Montagna</name>
</author>
<author>
<name sortKey="Casella, Cinzia" sort="Casella, Cinzia" uniqKey="Casella C" first="Cinzia" last="Casella">Cinzia Casella</name>
</author>
<author>
<name sortKey="Imyanitov, Evgeny N" sort="Imyanitov, Evgeny N" uniqKey="Imyanitov E" first="Evgeny N." last="Imyanitov">Evgeny N. Imyanitov</name>
</author>
<author>
<name sortKey="Janavicius, Ramunas" sort="Janavicius, Ramunas" uniqKey="Janavicius R" first="Ramunas" last="Janavicius">Ramunas Janavicius</name>
</author>
<author>
<name sortKey="Blanco, Ignacio" sort="Blanco, Ignacio" uniqKey="Blanco I" first="Ignacio" last="Blanco">Ignacio Blanco</name>
</author>
<author>
<name sortKey="Lazaro, Conxi" sort="Lazaro, Conxi" uniqKey="Lazaro C" first="Conxi" last="Lázaro">Conxi Lázaro</name>
</author>
<author>
<name sortKey="Moysich, Kirsten B" sort="Moysich, Kirsten B" uniqKey="Moysich K" first="Kirsten B." last="Moysich">Kirsten B. Moysich</name>
</author>
<author>
<name sortKey="Karlan, Beth Y" sort="Karlan, Beth Y" uniqKey="Karlan B" first="Beth Y." last="Karlan">Beth Y. Karlan</name>
</author>
<author>
<name sortKey="Gross, Jenny" sort="Gross, Jenny" uniqKey="Gross J" first="Jenny" last="Gross">Jenny Gross</name>
</author>
<author>
<name sortKey="Beattie, Mary S" sort="Beattie, Mary S" uniqKey="Beattie M" first="Mary S." last="Beattie">Mary S. Beattie</name>
</author>
<author>
<name sortKey="Schmutzler, Rita" sort="Schmutzler, Rita" uniqKey="Schmutzler R" first="Rita" last="Schmutzler">Rita Schmutzler</name>
</author>
<author>
<name sortKey="Wappenschmidt, Barbara" sort="Wappenschmidt, Barbara" uniqKey="Wappenschmidt B" first="Barbara" last="Wappenschmidt">Barbara Wappenschmidt</name>
</author>
<author>
<name sortKey="Meindl, Alfons" sort="Meindl, Alfons" uniqKey="Meindl A" first="Alfons" last="Meindl">Alfons Meindl</name>
</author>
<author>
<name sortKey="Ruehl, Ina" sort="Ruehl, Ina" uniqKey="Ruehl I" first="Ina" last="Ruehl">Ina Ruehl</name>
</author>
<author>
<name sortKey="Fiebig, Britta" sort="Fiebig, Britta" uniqKey="Fiebig B" first="Britta" last="Fiebig">Britta Fiebig</name>
</author>
<author>
<name sortKey="Sutter, Christian" sort="Sutter, Christian" uniqKey="Sutter C" first="Christian" last="Sutter">Christian Sutter</name>
</author>
<author>
<name sortKey="Arnold, Norbert" sort="Arnold, Norbert" uniqKey="Arnold N" first="Norbert" last="Arnold">Norbert Arnold</name>
</author>
<author>
<name sortKey="Deissler, Helmut" sort="Deissler, Helmut" uniqKey="Deissler H" first="Helmut" last="Deissler">Helmut Deissler</name>
</author>
<author>
<name sortKey="Varon Mateeva, Raymonda" sort="Varon Mateeva, Raymonda" uniqKey="Varon Mateeva R" first="Raymonda" last="Varon-Mateeva">Raymonda Varon-Mateeva</name>
</author>
<author>
<name sortKey="Kast, Karin" sort="Kast, Karin" uniqKey="Kast K" first="Karin" last="Kast">Karin Kast</name>
</author>
<author>
<name sortKey="Niederacher, Dieter" sort="Niederacher, Dieter" uniqKey="Niederacher D" first="Dieter" last="Niederacher">Dieter Niederacher</name>
</author>
<author>
<name sortKey="Gadzicki, Dorothea" sort="Gadzicki, Dorothea" uniqKey="Gadzicki D" first="Dorothea" last="Gadzicki">Dorothea Gadzicki</name>
</author>
<author>
<name sortKey="Caldes, Trinidad" sort="Caldes, Trinidad" uniqKey="Caldes T" first="Trinidad" last="Caldes">Trinidad Caldes</name>
</author>
<author>
<name sortKey="De La Hoya, Miguel" sort="De La Hoya, Miguel" uniqKey="De La Hoya M" first="Miguel" last="De La Hoya">Miguel De La Hoya</name>
</author>
<author>
<name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name>
</author>
<author>
<name sortKey="Aittom Ki, Kristiina" sort="Aittom Ki, Kristiina" uniqKey="Aittom Ki K" first="Kristiina" last="Aittom Ki">Kristiina Aittom Ki</name>
</author>
<author>
<name sortKey="Simard, Jacques" sort="Simard, Jacques" uniqKey="Simard J" first="Jacques" last="Simard">Jacques Simard</name>
</author>
<author>
<name sortKey="Soucy, Penny" sort="Soucy, Penny" uniqKey="Soucy P" first="Penny" last="Soucy">Penny Soucy</name>
</author>
<author>
<name sortKey="Spurdle, Amanda B" sort="Spurdle, Amanda B" uniqKey="Spurdle A" first="Amanda B." last="Spurdle">Amanda B. Spurdle</name>
</author>
<author>
<name sortKey="Holland, Helene" sort="Holland, Helene" uniqKey="Holland H" first="Helene" last="Holland">Helene Holland</name>
</author>
<author>
<name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name>
</author>
<author>
<name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F." last="Easton">Douglas F. Easton</name>
</author>
<author>
<name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C." last="Antoniou">Antonis C. Antoniou</name>
</author>
</analytic>
<series>
<title level="j">JNCI Journal of the National Cancer Institute</title>
<idno type="ISSN">0027-8874</idno>
<idno type="eISSN">1460-2105</idno>
<imprint>
<date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>Germline mutations in the
<italic>BRCA1</italic>
and
<italic>BRCA2</italic>
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
<italic>BRCA1</italic>
or
<italic>BRCA2</italic>
mutation carriers by use of data from the Consortium of Investigators of Modifiers of
<italic>BRCA1/2</italic>
.</p>
</sec>
<sec>
<title>Methods</title>
<p>We genotyped rs3814113 in 10 029
<italic>BRCA1</italic>
mutation carriers and 5837
<italic>BRCA2</italic>
mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided.</p>
</sec>
<sec>
<title>Results</title>
<p>The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among
<italic>BRCA1</italic>
mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85;
<italic>P</italic>
= 4.8 × 10
<sup>-9</sup>
) and
<italic>BRCA2</italic>
mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90;
<italic>P</italic>
= 5.5 × 10
<sup>-4</sup>
). This SNP was not associated with breast cancer risk among either
<italic>BRCA1</italic>
or
<italic>BRCA2</italic>
mutation carriers.
<italic>BRCA1</italic>
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%.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a
<italic>BRCA1</italic>
or
<italic>BRCA2</italic>
mutation.</p>
</sec>
</div>
</front>
</TEI>
<affiliations>
<list></list>
<tree>
<noCountry>
<name sortKey="Agnarsson, Bjarni A" sort="Agnarsson, Bjarni A" uniqKey="Agnarsson B" first="Bjarni A." last="Agnarsson">Bjarni A. Agnarsson</name>
<name sortKey="Aittom Ki, Kristiina" sort="Aittom Ki, Kristiina" uniqKey="Aittom Ki K" first="Kristiina" last="Aittom Ki">Kristiina Aittom Ki</name>
<name sortKey="Allavena, Anna" sort="Allavena, Anna" uniqKey="Allavena A" first="Anna" last="Allavena">Anna Allavena</name>
<name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L." last="Andrulis">Irene L. Andrulis</name>
<name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C." last="Antoniou">Antonis C. Antoniou</name>
<name sortKey="Arnold, Norbert" sort="Arnold, Norbert" uniqKey="Arnold N" first="Norbert" last="Arnold">Norbert Arnold</name>
<name sortKey="Arver, Brita" sort="Arver, Brita" uniqKey="Arver B" first="Brita" last="Arver">Brita Arver</name>
<name sortKey="Asperen, Christi J" sort="Asperen, Christi J" uniqKey="Asperen C" first="Christi J." last="Asperen">Christi J. Asperen</name>
<name sortKey="Ausems, Margreet G E M" sort="Ausems, Margreet G E M" uniqKey="Ausems M" first="Margreet G. E. M." last="Ausems">Margreet G. E. M. Ausems</name>
<name sortKey="Barile, Monica" sort="Barile, Monica" uniqKey="Barile M" first="Monica" last="Barile">Monica Barile</name>
<name sortKey="Barjhoux, Laure" sort="Barjhoux, Laure" uniqKey="Barjhoux L" first="Laure" last="Barjhoux">Laure Barjhoux</name>
<name sortKey="Beattie, Mary S" sort="Beattie, Mary S" uniqKey="Beattie M" first="Mary S." last="Beattie">Mary S. Beattie</name>
<name sortKey="Beesley, Jonathan" sort="Beesley, Jonathan" uniqKey="Beesley J" first="Jonathan" last="Beesley">Jonathan Beesley</name>
<name sortKey="Benitez, Javier" sort="Benitez, Javier" uniqKey="Benitez J" first="Javier" last="Benítez">Javier Benítez</name>
<name sortKey="Bignon, Yves Jean" sort="Bignon, Yves Jean" uniqKey="Bignon Y" first="Yves-Jean" last="Bignon">Yves-Jean Bignon</name>
<name sortKey="Blanco, Ignacio" sort="Blanco, Ignacio" uniqKey="Blanco I" first="Ignacio" last="Blanco">Ignacio Blanco</name>
<name sortKey="Blok, Marinus J" sort="Blok, Marinus J" uniqKey="Blok M" first="Marinus J." last="Blok">Marinus J. Blok</name>
<name sortKey="Bodmer, Danielle" sort="Bodmer, Danielle" uniqKey="Bodmer D" first="Danielle" last="Bodmer">Danielle Bodmer</name>
<name sortKey="Bonadona, Valerie" sort="Bonadona, Valerie" uniqKey="Bonadona V" first="Valérie" last="Bonadona">Valérie Bonadona</name>
<name sortKey="Borg, Ake" sort="Borg, Ake" uniqKey="Borg A" first="Ake" last="Borg">Ake Borg</name>
<name sortKey="Brewer, Carole" sort="Brewer, Carole" uniqKey="Brewer C" first="Carole" last="Brewer">Carole Brewer</name>
<name sortKey="Buys, Saundra S" sort="Buys, Saundra S" uniqKey="Buys S" first="Saundra S." last="Buys">Saundra S. Buys</name>
<name sortKey="Byrski, Tomasz" sort="Byrski, Tomasz" uniqKey="Byrski T" first="Tomasz" last="Byrski">Tomasz Byrski</name>
<name sortKey="Caldes, Trinidad" sort="Caldes, Trinidad" uniqKey="Caldes T" first="Trinidad" last="Caldes">Trinidad Caldes</name>
<name sortKey="Caligo, Maria Adelaide" sort="Caligo, Maria Adelaide" uniqKey="Caligo M" first="Maria Adelaide" last="Caligo">Maria Adelaide Caligo</name>
<name sortKey="Capra, Fabio" sort="Capra, Fabio" uniqKey="Capra F" first="Fabio" last="Capra">Fabio Capra</name>
<name sortKey="Casella, Cinzia" sort="Casella, Cinzia" uniqKey="Casella C" first="Cinzia" last="Casella">Cinzia Casella</name>
<name sortKey="Castera, Laurent" sort="Castera, Laurent" uniqKey="Castera L" first="Laurent" last="Castera">Laurent Castera</name>
<name sortKey="Chen, Xiaoqing" sort="Chen, Xiaoqing" uniqKey="Chen X" first="Xiaoqing" last="Chen">Xiaoqing Chen</name>
<name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name>
<name sortKey="Cole, Trevor" sort="Cole, Trevor" uniqKey="Cole T" first="Trevor" last="Cole">Trevor Cole</name>
<name sortKey="Collonge Rame, Marie Agnes" sort="Collonge Rame, Marie Agnes" uniqKey="Collonge Rame M" first="Marie-Agnès" last="Collonge-Rame">Marie-Agnès Collonge-Rame</name>
<name sortKey="Cook, Margaret" sort="Cook, Margaret" uniqKey="Cook M" first="Margaret" last="Cook">Margaret Cook</name>
<name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J." last="Couch">Fergus J. Couch</name>
<name sortKey="Cruger, Dorthe" sort="Cruger, Dorthe" uniqKey="Cruger D" first="Dorthe" last="Cruger">Dorthe Cruger</name>
<name sortKey="Cybulski, Cezary" sort="Cybulski, Cezary" uniqKey="Cybulski C" first="Cezary" last="Cybulski">Cezary Cybulski</name>
<name sortKey="D Bniak, Tadeusz" sort="D Bniak, Tadeusz" uniqKey="D Bniak T" first="Tadeusz" last="D Bniak">Tadeusz D Bniak</name>
<name sortKey="Daly, Mary B" sort="Daly, Mary B" uniqKey="Daly M" first="Mary B." last="Daly">Mary B. Daly</name>
<name sortKey="De La Hoya, Miguel" sort="De La Hoya, Miguel" uniqKey="De La Hoya M" first="Miguel" last="De La Hoya">Miguel De La Hoya</name>
<name sortKey="Deissler, Helmut" sort="Deissler, Helmut" uniqKey="Deissler H" first="Helmut" last="Deissler">Helmut Deissler</name>
<name sortKey="Ding, Yuan Chun" sort="Ding, Yuan Chun" uniqKey="Ding Y" first="Yuan Chun" last="Ding">Yuan Chun Ding</name>
<name sortKey="Domchek, Susan M" sort="Domchek, Susan M" uniqKey="Domchek S" first="Susan M." last="Domchek">Susan M. Domchek</name>
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<name sortKey="Dutra Clarke, Ana V C" sort="Dutra Clarke, Ana V C" uniqKey="Dutra Clarke A" first="Ana V. C." last="Dutra-Clarke">Ana V. C. Dutra-Clarke</name>
<name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F." last="Easton">Douglas F. Easton</name>
<name sortKey="Eeles, Ros" sort="Eeles, Ros" uniqKey="Eeles R" first="Ros" last="Eeles">Ros Eeles</name>
<name sortKey="Ejlertsen, Bent" sort="Ejlertsen, Bent" uniqKey="Ejlertsen B" first="Bent" last="Ejlertsen">Bent Ejlertsen</name>
<name sortKey="Evans, D Gareth" sort="Evans, D Gareth" uniqKey="Evans D" first="D. Gareth" last="Evans">D. Gareth Evans</name>
<name sortKey="Faivre, Laurence" sort="Faivre, Laurence" uniqKey="Faivre L" first="Laurence" last="Faivre">Laurence Faivre</name>
<name sortKey="Fert Ferrer, Sandra" sort="Fert Ferrer, Sandra" uniqKey="Fert Ferrer S" first="Sandra" last="Fert-Ferrer">Sandra Fert-Ferrer</name>
<name sortKey="Fiebig, Britta" sort="Fiebig, Britta" uniqKey="Fiebig B" first="Britta" last="Fiebig">Britta Fiebig</name>
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<name sortKey="Frost, Debra" sort="Frost, Debra" uniqKey="Frost D" first="Debra" last="Frost">Debra Frost</name>
<name sortKey="G Rski, Bohdan" sort="G Rski, Bohdan" uniqKey="G Rski B" first="Bohdan" last="G Rski">Bohdan G Rski</name>
<name sortKey="Gadzicki, Dorothea" sort="Gadzicki, Dorothea" uniqKey="Gadzicki D" first="Dorothea" last="Gadzicki">Dorothea Gadzicki</name>
<name sortKey="Gayther, Simon A" sort="Gayther, Simon A" uniqKey="Gayther S" first="Simon A." last="Gayther">Simon A. Gayther</name>
<name sortKey="Gerdes, Anne Marie" sort="Gerdes, Anne Marie" uniqKey="Gerdes A" first="Anne-Marie" last="Gerdes">Anne-Marie Gerdes</name>
<name sortKey="Gismondi, Viviana" sort="Gismondi, Viviana" uniqKey="Gismondi V" first="Viviana" last="Gismondi">Viviana Gismondi</name>
<name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name>
<name sortKey="Godwin, Andrew" sort="Godwin, Andrew" uniqKey="Godwin A" first="Andrew" last="Godwin">Andrew Godwin</name>
<name sortKey="Goldgar, David" sort="Goldgar, David" uniqKey="Goldgar D" first="David" last="Goldgar">David Goldgar</name>
<name sortKey="Greene, Mark H" sort="Greene, Mark H" uniqKey="Greene M" first="Mark H." last="Greene">Mark H. Greene</name>
<name sortKey="Gregory, Helen" sort="Gregory, Helen" uniqKey="Gregory H" first="Helen" last="Gregory">Helen Gregory</name>
<name sortKey="Gronwald, Jacek" sort="Gronwald, Jacek" uniqKey="Gronwald J" first="Jacek" last="Gronwald">Jacek Gronwald</name>
<name sortKey="Gross, Jenny" sort="Gross, Jenny" uniqKey="Gross J" first="Jenny" last="Gross">Jenny Gross</name>
<name sortKey="Hamann, Ute" sort="Hamann, Ute" uniqKey="Hamann U" first="Ute" last="Hamann">Ute Hamann</name>
<name sortKey="Hansen, Thomas V O" sort="Hansen, Thomas V O" uniqKey="Hansen T" first="Thomas V. O." last="Hansen">Thomas V. O. Hansen</name>
<name sortKey="Healey, Sue" sort="Healey, Sue" uniqKey="Healey S" first="Sue" last="Healey">Sue Healey</name>
<name sortKey="Hodgson, Shirley" sort="Hodgson, Shirley" uniqKey="Hodgson S" first="Shirley" last="Hodgson">Shirley Hodgson</name>
<name sortKey="Holland, Helene" sort="Holland, Helene" uniqKey="Holland H" first="Helene" last="Holland">Helene Holland</name>
<name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name>
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<name sortKey="Karlsson, Per" sort="Karlsson, Per" uniqKey="Karlsson P" first="Per" last="Karlsson">Per Karlsson</name>
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<name sortKey="Kristoffersson, Ulf" sort="Kristoffersson, Ulf" uniqKey="Kristoffersson U" first="Ulf" last="Kristoffersson">Ulf Kristoffersson</name>
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<name sortKey="Mai, Phuong L" sort="Mai, Phuong L" uniqKey="Mai P" first="Phuong L." last="Mai">Phuong L. Mai</name>
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</noCountry>
</tree>
</affiliations>
</record>

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