Abstract
| Original language | English |
|---|---|
| Journal | Nature Genetics |
| Volume | 47 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2015 |
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In: Nature Genetics, Vol. 47, No. 2, 02.2015.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Identification of six new susceptibility loci for invasive epithelial ovarian cancer.
AU - Tyrer, Jonathan
AU - Shen, Howard C
AU - Lawrenson, Kate
AU - Lee, Janet M
AU - Spindler, Tassja J
AU - Lin, Yvonne G
AU - Pejovic, Tanja
AU - Bean, Yukie
AU - Li, Qiyuan
AU - Coetzee, Simon
AU - Hazelett, Dennis
AU - Isaccs, Claudine
AU - Hein, Alexander
AU - Ekici, Arif B
AU - Beckmann, Matthias W
AU - Fasching, Peter A
AU - Lambrechts, Diether
AU - Van Nieuwenhuysen, Els
AU - Vergote, Ignace
AU - Lambrechts, Sandrina
AU - Doherty, Jennifer A
AU - Wicklund, Kristine G
AU - Rossing, Mary Anne
AU - Rudolph, Anja
AU - Chang-Claude, Jenny
AU - Wang-Gohrke, Shan
AU - Eilber, Ursula
AU - Lele, Shashi
AU - Wilkens, Lynne R
AU - Goodman, Marc T
AU - Thompson, Pamela J
AU - Shvetsov, Yurii B
AU - Runnebaum, Ingo B
AU - Dürst, Matthias
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N1 - 076113, Wellcome Trust, United KingdomC12292/A11174, Cancer Research UK, United KingdomC1287/A10118, Cancer Research UK, United KingdomP50 CA159981, NCI NIH HHS, United StatesR01 CA126841, NCI NIH HHS, United StatesR01 CA140323, NCI NIH HHS, United StatesU19-CA148112, NCI NIH HHS, United States
PY - 2015/2
Y1 - 2015/2
N2 - 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 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
AB - 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 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
U2 - 10.1038/ng.3185
DO - 10.1038/ng.3185
M3 - Article
C2 - 25581431
SN - 1061-4036
VL - 47
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -