Common variants at 19p13 are associated with susceptibility to ovarian cancer.
Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10⁻⁴ and P = 6 × 10⁻⁴, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10⁻⁹ and P = 4 × 10⁻¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.
Bolton
Kelly L
KL
Department of Oncology, University of Cambridge, Cambridge, UK.
Tyrer
Jonathan
J
Song
Honglin
H
Ramus
Susan J
SJ
Notaridou
Maria
M
Jones
Chris
C
Sher
Tanya
T
Gentry-Maharaj
Aleksandra
A
Wozniak
Eva
E
Tsai
Ya-Yu
YY
Weidhaas
Joanne
J
Paik
Daniel
D
Van Den Berg
David J
DJ
Stram
Daniel O
DO
Pearce
Celeste Leigh
CL
Wu
Anna H
AH
Brewster
Wendy
W
Anton-Culver
Hoda
H
Ziogas
Argyrios
A
Narod
Steven A
SA
Levine
Douglas A
DA
Kaye
Stanley B
SB
Brown
Robert
R
Paul
Jim
J
Flanagan
James
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Sieh
Weiva
W
McGuire
Valerie
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Whittemore
Alice S
AS
Campbell
Ian
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Gore
Martin E
ME
Lissowska
Jolanta
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Hanna P
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Medrek
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Gronwald
Jacek
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Jakubowska
Anna
A
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Nhu D
ND
Cook
Linda S
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Kelemen
Linda E
LE
Brooks-Wilson
Angela
A
Brook-Wilson
Angela
A
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Leon F A G
LF
Kiemeney
Lambertus A
LA
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Katja K H
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van Altena
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AM
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Ian
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Rachel T
RT
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Patricia G
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Schildkraut
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Edwin S
ES
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C
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RA
Cunningham
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JM
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EL
Fridley
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BL
Kruger-Kjaer
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Claus
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J
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BY
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RP
Odunsi
Kunle
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Kirsten B
KB
Baker
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Modugno
Francesmary
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Tuomas
T
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Nevanlinna
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I
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MT
Lurie
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Wang-Gohrke
Shan
S
Hein
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R
Chang-Claude
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J
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MA
Cushing-Haugen
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Doherty
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J
Chen
Chu
C
Rafnar
Thorunn
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MJ
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Kathryn L
KL
Hernandez
Dena
D
Cramer
Daniel W
DW
Vergote
Ignace
I
Amant
Frederic
F
Lambrechts
Diether
D
Despierre
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E
Fasching
Peter A
PA
Beckmann
Matthias W
MW
Thiel
Falk C
FC
Ekici
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AB
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Johnatty
Sharon E
SE
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PM
Beesley
Jonathan
J
Chanock
Stephen
S
Garcia-Closas
Montserrat
M
Sellers
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T
Easton
Douglas F
DF
Berchuck
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A
Chenevix-Trench
Georgia
G
Pharoah
Paul D P
PD
Gayther
Simon A
SA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; C540398:BABAM1 protein, human; D014408:Biomarkers, Tumor