Ontology highlight
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.
SUBMITTER: Ramus SJ
PROVIDER: S-EPMC3107565 | biostudies-literature | 2011 Jan
REPOSITORIES: biostudies-literature
Ramus Susan J SJ Kartsonaki Christiana C Gayther Simon A SA Pharoah Paul D P PD Sinilnikova Olga M OM Beesley Jonathan J Chen Xiaoqing X McGuffog Lesley L Healey Sue S Couch Fergus J FJ Wang Xianshu X Fredericksen Zachary Z Peterlongo Paolo P Manoukian Siranoush S Peissel Bernard B Zaffaroni Daniela D Roversi Gaia G Barile Monica M Viel Alessandra A Allavena Anna A Ottini Laura L Papi Laura L Gismondi Viviana V Capra Fabio F Radice Paolo P Greene Mark H MH Mai Phuong L PL Andrulis Irene L IL Glendon Gord G Ozcelik Hilmi H Thomassen Mads M Gerdes Anne-Marie AM Kruse Torben A TA Cruger Dorthe D Jensen Uffe Birk UB Caligo Maria Adelaide MA Olsson Håkan H Kristoffersson Ulf U Lindblom Annika A Arver Brita B Karlsson Per P Stenmark Askmalm Marie M Borg Ake A Neuhausen Susan L SL Ding Yuan Chun YC Nathanson Katherine L KL Domchek Susan M SM Jakubowska Anna A Lubiński Jan J Huzarski Tomasz T Byrski Tomasz T Gronwald Jacek J Górski Bohdan B Cybulski Cezary C Dębniak Tadeusz T Osorio Ana A Durán Mercedes M Tejada Maria-Isabel MI Benítez Javier J Hamann Ute U Rookus Matti A MA Verhoef Senno S Tilanus-Linthorst Madeleine A MA Vreeswijk Maaike P MP Bodmer Danielle D Ausems Margreet G E M MG van Os Theo A TA Asperen Christi J CJ Blok Marinus J MJ Meijers-Heijboer Hanne E J HE Peock Susan S Cook Margaret M Oliver Clare C Frost Debra D Dunning Alison M AM Evans D Gareth DG Eeles Ros R Pichert Gabriella G Cole Trevor T Hodgson Shirley S Brewer Carole C Morrison Patrick J PJ Porteous Mary M Kennedy M John MJ Rogers Mark T MT Side Lucy E LE Donaldson Alan A Gregory Helen H Godwin Andrew A Stoppa-Lyonnet Dominique D Moncoutier Virginie V Castera Laurent L Mazoyer Sylvie S Barjhoux Laure L Bonadona Valérie V Leroux Dominique D Faivre Laurence L Lidereau Rosette R Nogues Catherine C Bignon Yves-Jean YJ Prieur Fabienne F Collonge-Rame Marie-Agnès MA Venat-Bouvet Laurence L Fert-Ferrer Sandra S Miron Alex A Buys Saundra S SS Hopper John L JL Daly Mary B MB John Esther M EM Terry Mary Beth MB Goldgar David D Hansen Thomas v O Tv Jønson Lars L Ejlertsen Bent B Agnarsson Bjarni A BA Offit Kenneth K Kirchhoff Tomas T Vijai Joseph J Dutra-Clarke Ana V C AV Przybylo Jennifer A JA Montagna Marco M Casella Cinzia C Imyanitov Evgeny N EN Janavicius Ramunas R Blanco Ignacio I Lázaro Conxi C Moysich Kirsten B KB Karlan Beth Y BY Gross Jenny J Beattie Mary S MS Schmutzler Rita R Wappenschmidt Barbara B Meindl Alfons A Ruehl Ina I Fiebig Britta B Sutter Christian C Arnold Norbert N Deissler Helmut H Varon-Mateeva Raymonda R Kast Karin K Niederacher Dieter D Gadzicki Dorothea D Caldes Trinidad T de la Hoya Miguel M Nevanlinna Heli H Aittomäki Kristiina K Simard Jacques J Soucy Penny P Spurdle Amanda B AB Holland Helene H Chenevix-Trench Georgia G Easton Douglas F DF Antoniou Antonis C AC
Journal of the National Cancer Institute 20101217 2
<h4>Background</h4>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 o ...[more]