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Identification of six new susceptibility loci for invasive epithelial ovarian cancer

KB Kuchenbaecker, SJ Ramus, J Tyrer, A Lee, HC Shen, J Beesley, K Lawrenson, L McGuffog, S Healey, JM Lee, et al. (2015) NATURE GENETICS. 47(2). p.164-171
abstract
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.
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author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
BRCA2 MUTATION CARRIERS, GENOME-WIDE ASSOCIATION, ABO BLOOD-GROUP, BREAST-CANCER, GENETIC-VARIATION, COMMON VARIANTS, HUMAN ELG1, RISK, MYOPODIN, METAANALYSIS
journal title
NATURE GENETICS
Nature Genet.
volume
47
issue
2
pages
164 - 171
Web of Science type
Article
Web of Science id
000348694700012
JCR category
GENETICS & HEREDITY
JCR impact factor
31.616 (2015)
JCR rank
2/165 (2015)
JCR quartile
1 (2015)
ISSN
1061-4036
DOI
10.1038/ng.3185
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
5977261
handle
http://hdl.handle.net/1854/LU-5977261
date created
2015-06-05 12:26:57
date last changed
2016-12-19 15:43:29
@article{5977261,
  abstract     = {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 {\textlangle} 5 x 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.},
  author       = {Kuchenbaecker, KB and Ramus, SJ and Tyrer, J and Lee, A and Shen, HC and Beesley, J and Lawrenson, K and McGuffog, L and Healey, S and Lee, JM and Spindler, TJ and Lin, YG and Pejovic, T and Bean, Y and Li, Q and Coetzee, S and Hazelett, D and Miron, A and Southey, M and Terry, MB and Goldgar, DE and Buys, SS and Janavicius, R and Dorfling, CM and van Rensburg, EJ and Neuhausen, SL and Ding, YC and Hansen, TVO and Jonson, L and Gerdes, AM and Ejlertsen, B and Barrowdale, D and Dennis, J and Benitez, J and Osorio, A and Garcia, MJ and Komenaka, I and Weitzel, JN and Ganschow, P and Peterlongo, P and Bernard, L and Viel, A and Bonanni, B and Peissel, B and Manoukian, S and Radice, P and Papi, L and Ottini, L and Fostira, F and Konstantopoulou, I and Garber, J and Frost, D and Perkins, J and Platte, R and Ellis, S and Godwin, AK and Schmutzler, RK and Meindl, A and Engel, C and Sutter, C and Sinilnikova, OM and Damiola, F and Mazoyer, S and Stoppa-Lyonnet, D and Claes, Kathleen and De Leeneer, Kim and Kirk, J and Rodriguez, GC and Piedmonte, M and O'Malley, DM and de la Hoya, M and Caldes, T and Aittomaki, K and Nevanlinna, H and Collee, JM and Rookus, MA and Oosterwijk, JC and Tihomirova, L and Tung, N and Hamann, U and Isaccs, C and Tischkowitz, M and Imyanitov, EN and Caligo, MA and Campbe, IG and Hogervorst, FBL and Olah, E and Diez, O and Blanco, I and Brunet, J and Lazaroso, C and Pujana, MA and Jakubowska, A and Gronwald, J and Lubinski, J and Sukiennicki, G and Barkardottir, RB and Plante, M and Simard, J and Soucy, P and Montagna, M and Tognazzo, S and Teixeira, MR and Pankratz, VS and Wang, XS and Lindor, N and Szabo, CI and Kauff, N and Vijai, J and Aghajanian, CA and Pfeiler, G and Berger, A and Singer, CF and Tea, MK and Phelan, CM and Greene, MH and Mai, PL and Rennert, G and Mulligan, AM and Tchatchou, S and Andrulis, IL and Glendon, G and Toland, AE and Jensen, UB and Kruse, TA and Thomassen, M and Bojesen, A and Zidan, J and Friedman, E and Laitman, Y and Soller, M and Liljegren, A and Arver, B and Einbeigi, Z and Stenmark-Askmalm, M and Olopade, OI and Nussbaum, RL and Rebbeck, TR and Nathanson, KL and Domchek, SM and Lu, KH and Karlan, BY and Walsh, C and Lester, J and Hein, A and Ekici, AB and Beckmann, MW and Fasching, PA and Lambrechts, D and Van Nieuwenhuysen, E and Vergote, I and Lambrechts, S and Dicks, E and Doherty, JA and Wicklund, KG and Rossing, MA and Rudolph, A and Chang-Claude, J and Wang-Gohrke, S and Eilber, U and Moysich, KB and Odunsi, K and Sucheston, L and Lele, S and Wilkens, LR and Goodman, MT and Thompson, PJ and Shvetsov, YB and Runnebaum, IB and Durst, M and Hillemanns, P and Dork, T and Antonenkova, N and Bogdanova, N and Leminen, A and Pelttari, LM and Butzow, R and Modugno, F and Kelley, JL and Edwards, RP and Ness, RB and du Bois, A and Heitz, F and Schwaab, I and Harter, P and Matsuo, K and Hosono, S and Orsulic, S and Jensen, A and Kjaer, SK and Hogdall, E and Hasmad, HN and Azmi, MAN and Teo, SH and Woo, YL and Fridley, BL and Goode, EL and Cunningham, JM and Vierkant, RA and Bruinsma, F and Giles, GG and Liang, D and Hildebrandt, MAT and Wu, XF and Levine, DA and Bisogna, M and Berchuck, A and Iversen, ES and Schildkraut, JM and Concannon, P and Weber, RP and Cramer, DW and Terry, KL and Poole, EM and Tworoger, SS and Bandera, EV and Orlow, I and Olson, SH and Krakstad, C and Salvesen, HB and Tangen, IL and Bjorge, L and van Altena, AM and Aben, KKH and Kiemeney, LA and Massuger, LFAG and Kellar, M and Brooks-Wilson, A and Kelemen, LE and Cook, LS and Le, ND and Cybulski, C and Yang, H and Lissowska, J and Brinton, LA and Wentzensen, N and Hogdall, C and Lundvall, L and Nedergaard, L and Baker, H and Song, HL and Eccles, D and McNeish, I and Paul, J and Carty, K and Siddiqui, N and Glasspool, R and Whittemore, AS and Rothstein, JH and McGuire, V and Sieh, W and Ji, BT and Zheng, W and Shu, XO and Gao, YT and Rosen, B and Risch, HA and McLaughlin, JR and Narod, SA and Monteiro, AN and Chen, A and Lin, HY and Permuth-Wey, J and Sellers, TA and Tsai, YY and Chen, Z and Ziogas, A and Anton-Culver, H and Gentry-Maharaj, A and Menon, U and Harrington, P and Lee, AW and Wu, AH and Pearce, CL and Coetzee, G and Pike, MC and Dansonka-Mieszkowska, A and Timorek, A and Rzepecka, IK and Kupryjanczyk, J and Freedman, M and Noushmehr, H and Easton, DF and Offit, K and Couch, FJ and Gayther, S and Pharoah, PP and Antoniou, AC and Chenevix-Trench, G},
  issn         = {1061-4036},
  journal      = {NATURE GENETICS},
  keyword      = {BRCA2 MUTATION CARRIERS,GENOME-WIDE ASSOCIATION,ABO BLOOD-GROUP,BREAST-CANCER,GENETIC-VARIATION,COMMON VARIANTS,HUMAN ELG1,RISK,MYOPODIN,METAANALYSIS},
  language     = {eng},
  number       = {2},
  pages        = {164--171},
  title        = {Identification of six new susceptibility loci for invasive epithelial ovarian cancer},
  url          = {http://dx.doi.org/10.1038/ng.3185},
  volume       = {47},
  year         = {2015},
}

Chicago
Kuchenbaecker, KB, SJ Ramus, J Tyrer, A Lee, HC Shen, J Beesley, K Lawrenson, et al. 2015. “Identification of Six New Susceptibility Loci for Invasive Epithelial Ovarian Cancer.” Nature Genetics 47 (2): 164–171.
APA
Kuchenbaecker, K., Ramus, S., Tyrer, J., Lee, A., Shen, H., Beesley, J., Lawrenson, K., et al. (2015). Identification of six new susceptibility loci for invasive epithelial ovarian cancer. NATURE GENETICS, 47(2), 164–171.
Vancouver
1.
Kuchenbaecker K, Ramus S, Tyrer J, Lee A, Shen H, Beesley J, et al. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. NATURE GENETICS. 2015;47(2):164–71.
MLA
Kuchenbaecker, KB, SJ Ramus, J Tyrer, et al. “Identification of Six New Susceptibility Loci for Invasive Epithelial Ovarian Cancer.” NATURE GENETICS 47.2 (2015): 164–171. Print.