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Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Abstract

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.

Type Journal
ISBN 1546-1718 (Electronic) 1061-4036 (Linking)
Authors Phelan, C. M.; Kuchenbaecker, K. B.; Tyrer, J. P.; Kar, S. P.; Lawrenson, K.; Winham, S. J.; Dennis, J.; Pirie, A.; Riggan, M. J.; Chornokur, G.; Earp, M. A.; Lyra, P. C., Jr.; Lee, J. M.; Coetzee, S.; Beesley, J.; McGuffog, L.; Soucy, P.; Dicks, E.; Lee, A.; Barrowdale, D.; Lecarpentier, J.; Leslie, G.; Aalfs, C. M.; Aben, K. K.; Adams, M.; Adlard, J.; Andrulis, I. L.; Anton-Culver, H.; Antonenkova, N.; group, Aocs study; Aravantinos, G.; Arnold, N.; Arun, B. K.; Arver, B.; Azzollini, J.; Balmana, J.; Banerjee, S. N.; Barjhoux, L.; Barkardottir, R. B.; Bean, Y.; Beckmann, M. W.; Beeghly-Fadiel, A.; Benitez, J.; Bermisheva, M.; Bernardini, M. Q.; Birrer, M. J.; Bjorge, L.; Black, A.; Blankstein, K.; Blok, M. J.; Bodelon, C.; Bogdanova, N.; Bojesen, A.; Bonanni, B.; Borg, A.; Bradbury, A. R.; Brenton, J. D.; Brewer, C.; Brinton, L.; Broberg, P.; Brooks-Wilson, A.; Bruinsma, F.; Brunet, J.; Buecher, B.; Butzow, R.; Buys, S. S.; Caldes, T.; Caligo, M. A.; Campbell, I.; Cannioto, R.; Carney, M. E.; Cescon, T.; Chan, S. B.; Chang-Claude, J.; Chanock, S.; Chen, X. Q.; Chiew, Y. E.; Chiquette, J.; Chung, W. K.; Claes, K. B.; Conner, T.; Cook, L. S.; Cook, J.; Cramer, D. W.; Cunningham, J. M.; D'Aloisio, A. A.; Daly, M. B.; Damiola, F.; Damirovna, S. D.; Dansonka-Mieszkowska, A.; Dao, F.; Davidson, R.; DeFazio, A.; Delnatte, C.; Doheny, K. F.; Diez, O.; Ding, Y. C.; Doherty, J. A.; Domchek, S. M.; Dorfling, C. M., et al.
Publisher Name NATURE GENETICS
Published Date 2017-05-31 00:00:00
Published Volume 49
Published Issue 5
Published Pages 680-691
Status Published in-print
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28346442