A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2.
Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).
Song
Honglin
H
Cancer Research UK Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
Ramus
Susan J
SJ
Tyrer
Jonathan
J
Bolton
Kelly L
KL
Gentry-Maharaj
Aleksandra
A
Wozniak
Eva
E
Anton-Culver
Hoda
H
Chang-Claude
Jenny
J
Cramer
Daniel W
DW
DiCioccio
Richard
R
Dörk
Thilo
T
Goode
Ellen L
EL
Goodman
Marc T
MT
Schildkraut
Joellen M
JM
Sellers
Thomas
T
Baglietto
Laura
L
Beckmann
Matthias W
MW
Beesley
Jonathan
J
Blaakaer
Jan
J
Carney
Michael E
ME
Chanock
Stephen
S
Chen
Zhihua
Z
Cunningham
Julie M
JM
Dicks
Ed
E
Doherty
Jennifer A
JA
Dürst
Matthias
M
Ekici
Arif B
AB
Fenstermacher
David
D
Fridley
Brooke L
BL
Giles
Graham
G
Gore
Martin E
ME
De Vivo
Immaculata
I
Hillemanns
Peter
P
Hogdall
Claus
C
Hogdall
Estrid
E
Iversen
Edwin S
ES
Jacobs
Ian J
IJ
Jakubowska
Anna
A
Li
Dong
D
Lissowska
Jolanta
J
Lubiński
Jan
J
Lurie
Galina
G
McGuire
Valerie
V
McLaughlin
John
J
Medrek
Krzysztof
K
Moorman
Patricia G
PG
Moysich
Kirsten
K
Narod
Steven
S
Phelan
Catherine
C
Pye
Carole
C
Risch
Harvey
H
Runnebaum
Ingo B
IB
Severi
Gianluca
G
Southey
Melissa
M
Stram
Daniel O
DO
Thiel
Falk C
FC
Terry
Kathryn L
KL
Tsai
Ya-Yu
YY
Tworoger
Shelley S
SS
Van Den Berg
David J
DJ
Vierkant
Robert A
RA
Wang-Gohrke
Shan
S
Webb
Penelope M
PM
Wilkens
Lynne R
LR
Wu
Anna H
AH
Yang
Hannah
H
Brewster
Wendy
W
Ziogas
Argyrios
A
Houlston
Richard
R
Tomlinson
Ian
I
Whittemore
Alice S
AS
Rossing
Mary Anne
MA
Ponder
Bruce A J
BA
Pearce
Celeste Leigh
CL
Ness
Roberta B
RB
Menon
Usha
U
Kjaer
Susanne Krüger
SK
Gronwald
Jacek
J
Garcia-Closas
Montserrat
M
Fasching
Peter A
PA
Easton
Douglas F
DF
Chenevix-Trench
Georgia
G
Berchuck
Andrew
A
Pharoah
Paul D P
PD
Gayther
Simon A
SA
D000483:Alleles; D001315:Australia; D001483:Base Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D016001:Confidence Intervals; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014481:United States; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data