title: Consortium analysis of 7 candidate SNPs for ovarian cancer.
abstract: 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.
authors.affiliation: Translational Research Laboratory, University College London EGA Institute for Women's Health, London, United Kingdom.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.affiliation: College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.affiliation: The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Johnatty
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, CA.
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, CA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Van Den Berg
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, CA.
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, CA.
authors.forename: Celeste Leigh
authors.initials: CL
authors.lastname: Pearce
authors.affiliation: Gynaecological Cancer Research Centre, University College London, EGA Institute for Women's Health, London, United Kingdom.
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.affiliation: Gynaecological Cancer Research Centre, University College London, EGA Institute for Women's Health, London, United Kingdom.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.affiliation: Translational Research Laboratory, University College London EGA Institute for Women's Health, London, United Kingdom.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Richard A
authors.initials: RA
authors.lastname: DiCioccio
authors.affiliation: Stanford University School of Medicine, Stanford, CA.
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.affiliation: Stanford University School of Medicine, Stanford, CA.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.affiliation: Cancer Research United Kingdom Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.affiliation: Cancer Research United Kingdom Genetic Epidemiology Unit, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.affiliation: Cancer Research United Kingdom Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
authors.forename: Paul D P
authors.initials: PDP
authors.lastname: Pharoah
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.affiliation: Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
authors.forename: Louise
authors.initials: L
authors.lastname: Brinton
authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC.
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.affiliation: Department of Community and Family Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Moorman
authors.affiliation: Department of Community and Family Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.affiliation: College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.affiliation: College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Mark
authors.initials: M
authors.lastname: Liebow
authors.affiliation: Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Susanne Krüger
authors.initials: SK
authors.lastname: Kjaer
authors.affiliation: Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Hogdall
authors.affiliation: Rigshospitalet, The Juliane Marie Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Hogdall
authors.affiliation: Aarhus University Hospital, Skejby, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Blaakaer
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Moysich
authors.affiliation: Magee-Womens Hospital, Pittsburgh, PA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Edwards
authors.affiliation: Cancer Research Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Carney
authors.affiliation: Cancer Research Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Galina
authors.initials: G
authors.lastname: Lurie
authors.affiliation: Cancer Research Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.affiliation: University of Ulm, Ulm, Germany.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang-Gohrke
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Kropp
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.affiliation: The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beesley
authors.affiliation: The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.affiliation: College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
mesh_terms: 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
chemical_list: 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