Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Karoline B. Kuchenbaecker, Susan J. Ramus, Jonathan Tyrer, Andrew Lee, Howard C. Shen, Jonathan Beesley, Kate Lawrenson, Lesley McGuffog, Sue Healey, Janet M. Lee, Tassja J. Spindler, Yvonne G. Lin, Tanja Pejovic, Yukie Bean, Qiyuan Li, Simon Coetzee, Dennis Hazelett, Alexander Miron, Melissa Southey, Mary Beth TerryDavid E. Goldgar, Saundra S. Buys, Ramunas Janavicius, Cecilia M. Dorfling, Elizabeth J. van Rensburg, Susan L. Neuhausen, Yuan Chun Ding, Thomas V. O. Hansen, Lars Jonson, Anne-Marie Gerdes, Bent Ejlertsen, Daniel Barrowdale, Joe Dennis, Javier Benitez, Ana Osorio, Maria Jose Garcia, Ian Komenaka, Jeffrey N. Weitzel, Pamela Ganschow, Paolo Peterlongo, Loris Bernard, Alessandra Viel, Bernardo Bonanni, Bernard Peissel, Siranoush Manoukian, Paolo Radice, Laura Papi, Laura Ottini, Florentia Fostira, Jan C. Oosterwijk, EMBRACE, GEMO Study Collaborators, Breast Cancer Family Registry, HEBON, kConFab Investigators, Australian Canc Study Ovarian Canc, Australian Ovarian Canc Study Grp, Consortium Invest Modifiers BRCA1

OnderzoeksoutputAcademicpeer review

159 Citaten (Scopus)

Samenvatting

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P <5 x 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

Originele taal-2English
Pagina's (van-tot)164-171
Aantal pagina's8
TijdschriftNature Genetics
Volume47
Nummer van het tijdschrift2
DOI's
StatusPublished - feb-2015

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