title: Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk.
abstract: BACKGROUND
  Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.
  
  
  METHODS
  In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
  
  
  RESULTS
  The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
  
  
  CONCLUSIONS
  These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
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authors.lastname: Schernhammer
authors.affiliation: Institut für Humangenetik, Wiesbaden, Germany.
authors.forename: Ira
authors.initials: I
authors.lastname: Schwaab
authors.affiliation: Epidemiology Center and Vanderbilt, Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, United States of America.
authors.forename: Yurii B
authors.initials: YB
authors.lastname: Shvetsov
authors.affiliation: Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Siddiqui
authors.affiliation: Department of Health Research and Policy- Epidemiology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Weiva
authors.initials: W
authors.lastname: Sieh
authors.affiliation: Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Pathology, the University of Melbourne, Parkville, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Department of Gynecologic Oncology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Spiewankiewicz
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Lara
authors.initials: L
authors.lastname: Sucheston
authors.affiliation: Cancer Research Initiatives Foundation, Sime Darby Medical Center, Subang Jaya, Malaysia; University Malaya Cancer Research Institute, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Maylaysia.
authors.forename: Soo-Hwang
authors.initials: SH
authors.lastname: Teo
authors.affiliation: Obstetrics and Gynecology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.affiliation: Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Thompson
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Thomsen
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Ingvild L
authors.initials: IL
authors.lastname: Tangen
authors.affiliation: Obstetrics and Gynecology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.affiliation: Department of Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Anne M
authors.initials: AM
authors.lastname: van Altena
authors.affiliation: Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Walsh
authors.affiliation: German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang-Gohrke
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Department of Health Research and Policy- Epidemiology, Stanford University School of Medicine, Stanford, California, United States of America.
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authors.initials: AS
authors.lastname: Whittemore
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, United States of America.
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authors.initials: KG
authors.lastname: Wicklund
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, United States of America.
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yin-Ling
authors.initials: YL
authors.lastname: Woo
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
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authors.lastname: Yang
authors.affiliation: Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Wei
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authors.affiliation: Genetic Epidemiology Research Institute, Center for Cancer Genetics Research and Prevention, University of California Irvine, Irvine, California, United States of America.
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authors.affiliation: Cancer Research Initiatives Foundation, Sime Darby Medical Center, Subang Jaya, Malaysia.
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authors.initials: HN
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authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, United States of America.
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authors.initials: A
authors.lastname: Berchuck
authors.affiliation: Department of Statistics, Duke University, Durham, North Carolina, United States of America.
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authors.initials: ES
authors.lastname: Iversen
authors.affiliation: Cancer Prevention, Detection & Control Research Program, Duke Cancer Institute, Durham, North Carolina, United States of America.
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authors.initials: JM
authors.lastname: Schildkraut
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
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authors.initials: SJ
authors.lastname: Ramus
authors.affiliation: Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America.
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authors.initials: EL
authors.lastname: Goode
authors.affiliation: Division of Population Sciences, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.
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authors.initials: AN
authors.lastname: Monteiro
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.affiliation: Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.affiliation: Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.affiliation: Division of Population Sciences, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.affiliation: Division of Population Sciences, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phelan
mesh_terms: D001741:Black or African American; D000483:Alleles; D001213:Asian; D001692:Biological Transport; D000077216:Carcinoma, Ovarian Epithelial; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D002352:Carrier Proteins