ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study.
We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope 1 (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95% CI, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer.
Doherty
Jennifer A
JA
Program in Epidemiology (M4-C308), Fred Hutchinson Cancer Research Center, PO Box 19024, Seattle, WA 98109-1024, USA. jdoherty@fhcrc.org
Rossing
Mary Anne
MA
Cushing-Haugen
Kara L
KL
Chen
Chu
C
Van Den Berg
David J
DJ
Wu
Anna H
AH
Pike
Malcolm C
MC
Ness
Roberta B
RB
Moysich
Kirsten
K
Chenevix-Trench
Georgia
G
Beesley
Jonathan
J
Webb
Penelope M
PM
Chang-Claude
Jenny
J
Wang-Gohrke
Shan
S
Goodman
Marc T
MT
Lurie
Galina
G
Thompson
Pamela J
PJ
Carney
Michael E
ME
Hogdall
Estrid
E
Kjaer
Susanne Kruger
SK
Hogdall
Claus
C
Goode
Ellen L
EL
Cunningham
Julie M
JM
Fridley
Brooke L
BL
Vierkant
Robert A
RA
Berchuck
Andrew
A
Moorman
Patricia G
PG
Schildkraut
Joellen M
JM
Palmieri
Rachel T
RT
Cramer
Daniel W
DW
Terry
Kathryn L
KL
Yang
Hannah P
HP
Garcia-Closas
Montserrat
M
Chanock
Stephen
S
Lissowska
Jolanta
J
Song
Honglin
H
Pharoah
Paul D P
PD
Shah
Mitul
M
Perkins
Barbara
B
McGuire
Valerie
V
Whittemore
Alice S
AS
Di Cioccio
Richard A
RA
Gentry-Maharaj
Aleksandra
A
Menon
Usha
U
Gayther
Simon A
SA
Ramus
Susan J
SJ
Ziogas
Argyrios
A
Brewster
Wendy
W
Anton-Culver
Hoda
H
Pearce
Celeste Leigh
CL
D014408:Biomarkers, Tumor / Q000235:genetics; D003598:Cytoskeletal Proteins; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human