title: A targeted genetic association study of epithelial ovarian cancer susceptibility.
abstract: BACKGROUND
  Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci.
  
  
  RESULTS
  At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5x10(-8)), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10-6).
  
  
  METHODS
  A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure.
  
  
  CONCLUSIONS
  Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance.
authors: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
authors: Madalene
authors: M
authors: Earp
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Stacey J
authors: SJ
authors: Winham
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Nicholas
authors: N
authors: Larson
authors: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors: Jennifer B
authors: JB
authors: Permuth
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Hugues
authors: H
authors: Sicotte
authors: Department of Cancer Biology, University of Kansas Cancer Center, Kansas City, KS, USA.
authors: Jeremy
authors: J
authors: Chien
authors: Department of Epidemiology, University of California Irvine, Irvine, CA, USA.
authors: Hoda
authors: H
authors: Anton-Culver
authors: Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors: Elisa V
authors: EV
authors: Bandera
authors: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors: Andrew
authors: A
authors: Berchuck
authors: Division of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM, USA.
authors: Linda S
authors: LS
authors: Cook
authors: Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors: Daniel
authors: D
authors: Cramer
authors: Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Jennifer A
authors: JA
authors: Doherty
authors: Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors: Marc T
authors: MT
authors: Goodman
authors: Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Douglas A
authors: DA
authors: Levine
authors: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors: Alvaro N A
authors: AN
authors: Monteiro
authors: The University of Texas School of Public Health, Houston, TX, USA.
authors: Roberta B
authors: RB
authors: Ness
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Celeste L
authors: CL
authors: Pearce
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Mary Anne
authors: MA
authors: Rossing
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.|Channing Division of Network Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
authors: Shelley S
authors: SS
authors: Tworoger
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Nicolas
authors: N
authors: Wentzensen
authors: Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Maria
authors: M
authors: Bisogna
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Louise
authors: L
authors: Brinton
authors: Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.|Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
authors: Angela
authors: A
authors: Brooks-Wilson
authors: Clinical and Translational Research Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors: Michael E
authors: ME
authors: Carney
authors: Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Julie M
authors: JM
authors: Cunningham
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Robert P
authors: RP
authors: Edwards
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Zachary C
authors: ZC
authors: Fogarty
authors: Department of Statistical Science, Duke University, Durham, NC, USA.
authors: Edwin S
authors: ES
authors: Iversen
authors: Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, MA, USA.
authors: Peter
authors: P
authors: Kraft
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Melissa C
authors: MC
authors: Larson
authors: Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
authors: Nhu D
authors: ND
authors: Le
authors: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors: Hui-Yi
authors: HY
authors: Lin
authors: Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland.
authors: Jolanta
authors: J
authors: Lissowska
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.|Cancer Research Program, Magee-Women's Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors: Francesmary
authors: F
authors: Modugno
authors: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, US.
authors: Kirsten B
authors: KB
authors: Moysich
authors: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Sara H
authors: SH
authors: Olson
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, US.
authors: Malcolm C
authors: MC
authors: Pike
authors: Channing Division of Network Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
authors: Elizabeth M
authors: EM
authors: Poole
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: David N
authors: DN
authors: Rider
authors: Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors: Kathryn L
authors: KL
authors: Terry
authors: Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors: Pamela J
authors: PJ
authors: Thompson
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: David
authors: D
authors: van den Berg
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Robert A
authors: RA
authors: Vierkant
authors: Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Allison F
authors: AF
authors: Vitonis
authors: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors: Lynne R
authors: LR
authors: Wilkens
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Anna H
authors: AH
authors: Wu
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Hannah P
authors: HP
authors: Yang
authors: Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, CA, USA.
authors: Argyrios
authors: A
authors: Ziogas
authors: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors: Catherine M
authors: CM
authors: Phelan
authors: Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA.|Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute, Durham, NC, USA.
authors: Joellen M
authors: JM
authors: Schildkraut
authors: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors: Yian Ann
authors: YA
authors: Chen
authors: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors: Thomas A
authors: TA
authors: Sellers
authors: Kansas IDeA Network of Biomedical Research Excellence Bioinformatics Core, University of Kansas Cancer Center, Kansas City, KS, USA.
authors: Brooke L
authors: BL
authors: Fridley
authors: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
authors: Ellen L
authors: EL
authors: Goode
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: NF-κB; genetic association; high-grade serous carcinoma; ovarian cancer; susceptibility loci