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Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
Author(s) -
Ramus Susan J.,
Antoniou Antonis C.,
Kuchenbaecker Karoline B.,
Soucy Penny,
Beesley Jonathan,
Chen Xiaoqing,
McGuffog Lesley,
Sinilnikova Olga M.,
Healey Sue,
Barrowdale Daniel,
Lee Andrew,
Thomassen Mads,
Gerdes AnneMarie,
Kruse Torben A.,
Jensen Uffe Birk,
Skytte AnneBine,
Caligo Maria A.,
Liljegren Annelie,
Lindblom Annika,
Olsson Håkan,
Kristoffersson Ulf,
StenmarkAskmalm Marie,
Melin Beatrice,
Domchek Susan M.,
Nathanson Katherine L.,
Rebbeck Timothy R.,
Jakubowska Anna,
Lubinski Jan,
Jaworska Katarzyna,
Durda Katarzyna,
Złowocka Elżbieta,
Gronwald Jacek,
Huzarski Tomasz,
Byrski Tomasz,
Cybulski Cezary,
ToloczkoGrabarek Aleksandra,
Osorio Ana,
Benitez Javier,
Duran Mercedes,
Tejada MariaIsabel,
Hamann Ute,
Rookus Matti,
van Leeuwen Flora E.,
Aalfs Cora M.,
MeijersHeijboer Hanne E.J.,
van Asperen Christi J.,
van Roozendaal K.E.P.,
Hoogerbrugge Nicoline,
Collée J. Margriet,
Kriege Mieke,
van der Luijt Rob B.,
Peock Susan,
Frost Debra,
Ellis Steve D.,
Platte Radka,
Fineberg Elena,
Evans D. Gareth,
Lalloo Fiona,
Jacobs Chris,
Eeles Ros,
Adlard Julian,
Davidson Rosemarie,
Eccles Diana,
Cole Trevor,
Cook Jackie,
Paterson Joan,
Douglas Fiona,
Brewer Carole,
Hodgson Shirley,
Morrison Patrick J.,
Walker Lisa,
Porteous Mary E.,
Kennedy M. John,
Pathak Harsh,
Godwin Andrew K.,
StoppaLyonnet Dominique,
CauxMoncoutier Virginie,
de Pauw Antoine,
GauthierVillars Marion,
Mazoyer Sylvie,
Léoné Mélanie,
Calender Alain,
Lasset Christine,
Bonadona Valérie,
Hardouin Agnès,
Berthet Pascaline,
Big YvesJean,
Uhrhammer Nancy,
Faivre Laurence,
Loustalot Catherine,
Buys Saundra,
Daly Mary,
Miron Alex,
Beth Terry Mary,
Chung Wendy K.,
John Esther M,
Southey Melissa,
Goldgar David,
Singer Christian F.,
Tea MuyKheng,
Pfeiler Georg,
FinkRetter Anneliese,
Hansen Thomas v. O.,
Ejlertsen Bent,
Johannsson Oskar Th.,
Offit Kenneth,
Kirchhoff Tomas,
Gaudet Mia M.,
Vijai Joseph,
Robson Mark,
Piedmonte Marion,
Phillips KellyAnne,
Van Le Linda,
Hoffman James S,
Toland Amanda Ewart,
Montagna Marco,
Tognazzo Silvia,
Imyanitov Evgeny,
Isaacs Claudine,
Janavicius Ramunas,
Lazaro Conxi,
Blanco Ignacio,
Tornero Eva,
Navarro Matilde,
Moysich Kirsten B.,
Karlan Beth Y.,
Gross Jenny,
Olah Edith,
Vaszko Tibor,
Teo SooHwang,
Ganz Patricia A.,
Beattie Mary S.,
Dorfling Cecelia M,
van Rensburg Elizabeth J.,
Diez Orland,
Kwong Ava,
Schmutzler Rita K.,
Wappenschmidt Barbara,
Engel Christoph,
Meindl Alfons,
Ditsch Nina,
Arnold Norbert,
Heidemann Simone,
Niederacher Dieter,
PreislerAdams Sabine,
Gadzicki Dorotehea,
VaronMateeva Raymonda,
Deissler Helmut,
Gehrig Andrea,
Sutter Christian,
Kast Karin,
Fiebig Britta,
Schäfer Dieter,
Caldes Trinidad,
de la Hoya Miguel,
Nevanlinna Heli,
Aittomäki Kristiina,
Plante Marie,
Spurdle Amanda B.,
Neuhausen Susan L.,
Ding Yuan Chun,
Wang Xianshu,
Lindor Noralane,
Fredericksen Zachary,
Pankratz V. Shane,
Peterlongo Paolo,
Manoukian Siranoush,
Peissel Bernard,
Zaffaroni Daniela,
Bonanni Bernardo,
Bernard Loris,
Dolcetti Riccardo,
Papi Laura,
Ottini Laura,
Radice Paolo,
Greene Mark H.,
Mai Phuong L.,
Andrulis Irene L.,
Glendon Gord,
Ozcelik Hilmi,
Pharoah Paul D.P.,
Gayther Simon A.,
Simard Jacques,
Easton Douglas F.,
Couch Fergus J.,
ChenevixTrench Georgia
Publication year - 2012
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22025
Subject(s) - ovarian cancer , biology , odds ratio , single nucleotide polymorphism , breast cancer , hazard ratio , oncology , allele , medicine , population , genome wide association study , cancer , genetics , gynecology , genotype , confidence interval , gene , environmental health
Abstract Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome‐wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single‐nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per‐allele hazard ratio (HR) = 0.81 (95% CI: 0.67–0.98) P‐trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21–1.83) P‐trend = 1.8 × 10 −4 , rs717852 HR = 1.25 (95% CI: 1.10–1.42) P‐trend = 6.6 × 10 −4 , rs9303542 HR = 1.16 (95% CI: 1.02–1.33) P‐trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per‐allele HR = 0.89 (95% CI: 0.81–0.99) P‐trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10–1.42) P‐trend = 6.1 × 10 −4 . The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. Hum Mutat 33:690–702, 2012. © 2012 Wiley Periodicals, Inc.