作者
Catherine M. Phelan,Karoline Kuchenbaecker,Jonathan Tyrer,Siddhartha Kar,Kate Lawrenson,Stacey J. Winham,Joe Dennis,Ailith Pirie,Marjorie J. Riggan,Ganna Chornokur,Madalene A. Earp,Paulo C. Lyra,Janet M. Lee,Simon G. Coetzee,Jonathan Beesley,Lesley McGuffog,Penny Soucy,Ed Dicks,Andrew Lee,Daniel Barrowdale,Julie Lecarpentier,Goska Leslie,Cora M. Aalfs,Katja K.H. Aben,M. W. Adams,Julian Adlard,Irene L. Andrulis,Hoda Anton‐Culver,Natalia Antonenkova,Gerasimos Aravantinos,Norbert Arnold,Banu K. Arun,Brita Arver,Jacopo Azzollini,Judith Balmañà,Susana Banerjee,Laure Barjhoux,Rósa B. Barkardóttir,Yukie T. Bean,Matthias W. Beckmann,Alicia Beeghly–Fadiel,Javier Benı́tez,Marina Bermisheva,Marcus Q. Bernardini,Michael J. Birrer,Line Bjørge,Amanda Black,Kenneth Bruce Blankstein,Marinus J. Blok,Clara Bodelón,Natalia Bogdanova,Anders Bojesen,Bernardo Bonanni,Åke Borg,Angela R. Bradbury,James D. Brenton,Carole Brewer,Louise A. Brinton,Per Broberg,Angela Brooks‐Wilson,Fiona Bruinsma,Joan Brunet,Benedetto Bruno,Ralf Bützow,Saundra S. Buys,Trinidad Caldés,Maria Adelaide Caligo,Ian G. Campbell,Rikki A. Cannioto,Michael E. Carney,Terence Cescon,Salina Chan,Jenny Chang‐Claude,Stephen J. Chanock,Xiao Qing Chen,Yoke-Eng Chiew,Jocelyne Chiquette,Wendy K. Chung,Kathleen Claes,Thomas Conner,Linda S. Cook,Jackie Cook,Daniel W. Cramer,Julie M. Cunningham,Aimee A. D’Aloisio,Mary B. Daly,Francesca Damiola,Sakaeva Dina Damirovna,Agnieszka Dansonka-Mieszkowska,Fanny Dao,Rosemarie Davidson,Anna deFazio,Capucine Delnatte,Kimberly F. Doheny,Orland Díez,Yuan Chun Ding,Jennifer A. Doherty,Susan M. Domchek,Cecilia M. Dorfling,Thilo Dörk
摘要
Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1. To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.