Consortium analysis of 7 candidate SNPs for ovarian cancer.
The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.
Ramus
Susan J
SJ
Translational Research Laboratory, University College London EGA Institute for Women's Health, London, United Kingdom.
Vierkant
Robert A
RA
College of Medicine, Mayo Clinic, Rochester, MN.
Johnatty
Sharon E
SE
The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
Pike
Malcolm C
MC
University of Southern California, Keck School of Medicine, Los Angeles, CA.
Van Den Berg
David J
DJ
University of Southern California, Keck School of Medicine, Los Angeles, CA.
Wu
Anna H
AH
University of Southern California, Keck School of Medicine, Los Angeles, CA.
Pearce
Celeste Leigh
CL
University of Southern California, Keck School of Medicine, Los Angeles, CA.
Menon
Usha
U
Gynaecological Cancer Research Centre, University College London, EGA Institute for Women's Health, London, United Kingdom.
Gentry-Maharaj
Aleksandra
A
Gynaecological Cancer Research Centre, University College London, EGA Institute for Women's Health, London, United Kingdom.
Gayther
Simon A
SA
Translational Research Laboratory, University College London EGA Institute for Women's Health, London, United Kingdom.
DiCioccio
Richard A
RA
Roswell Park Cancer Institute, Buffalo, NY.
McGuire
Valerie
V
Stanford University School of Medicine, Stanford, CA.
Whittemore
Alice S
AS
Stanford University School of Medicine, Stanford, CA.
Song
Honglin
H
Cancer Research United Kingdom Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
Easton
Douglas F
DF
Cancer Research United Kingdom Genetic Epidemiology Unit, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
Pharoah
Paul D P
PDP
Cancer Research United Kingdom Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
Garcia-Closas
Montserrat
M
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Chanock
Stephen
S
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Lissowska
Jolanta
J
Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
Brinton
Louise
L
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Terry
Kathryn L
KL
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA.
Cramer
Daniel W
DW
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA.
Tworoger
Shelley S
SS
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Hankinson
Susan E
SE
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Berchuck
Andrew
A
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC.
Moorman
Patricia G
PG
Department of Community and Family Medicine, Duke University Medical Center, Durham, NC.
Schildkraut
Joellen M
JM
Department of Community and Family Medicine, Duke University Medical Center, Durham, NC.
Cunningham
Julie M
JM
College of Medicine, Mayo Clinic, Rochester, MN.
Liebow
Mark
M
College of Medicine, Mayo Clinic, Rochester, MN.
Kjaer
Susanne Krüger
SK
Danish Cancer Society, Copenhagen, Denmark.
Hogdall
Estrid
E
Danish Cancer Society, Copenhagen, Denmark.
Hogdall
Claus
C
Rigshospitalet, The Juliane Marie Centre, University of Copenhagen, Copenhagen, Denmark.
Blaakaer
Jan
J
Aarhus University Hospital, Skejby, Denmark.
Ness
Roberta B
RB
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Moysich
Kirsten B
KB
Roswell Park Cancer Institute, Buffalo, NY.
Edwards
Robert P
RP
Magee-Womens Hospital, Pittsburgh, PA.
Carney
Michael E
ME
Cancer Research Center, University of Hawaii, Honolulu, Hawaii.
Lurie
Galina
G
Cancer Research Center, University of Hawaii, Honolulu, Hawaii.
Goodman
Marc T
MT
Cancer Research Center, University of Hawaii, Honolulu, Hawaii.
Wang-Gohrke
Shan
S
University of Ulm, Ulm, Germany.
Kropp
Silke
S
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chang-Claude
Jenny
J
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Webb
Penelope M
PM
The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
Chen
Xiaoqing
X
The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
Beesley
Jonathan
J
The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
Chenevix-Trench
Georgia
G
The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
Goode
Ellen L
EL
College of Medicine, Mayo Clinic, Rochester, MN.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D064096:Aurora Kinase A; D064127:Aurora Kinases; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D002277:Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D044465:White People / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D053773:Transforming Growth Factor beta1; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C505530:CASP8 protein, human; D053181:Caspase 8