Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

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Details zur Publikation

Autor(en): Chornokur G, Lin HY, Tyrer JP, Lawrenson K, Dennis J, Amankwah EK, Qu X, Tsai YY, Jim HSL, Chen Z, Chen AY, Permuth-Wey J, Aben KKH, Anton-Culver H, Antonenkova N, Bruinsma F, Bandera EV, Bean YT, Beckmann M, Bisogna M, Bjorge L, Bogdanova N, Brinton LA, Brooks-Wilson A, Bunker CH, Butzow R, Campbell IG, Carty K, Chang-Claude J, Cook LS, Cramer DW, Cunningham JM, Cybulski C, Dansonka-Mieszkowska A, Du Bois A, Despierre E, Dicks E, Doherty JA, Dork T, Durst M, Easton DF, Eccles DM, Edwards RP, Ekici AB, Fasching PA, Fridley BL, Gao YT, Gentry-Maharaj A, Giles GG, Glasspool R, Goodman MT, Gronwald J, Harrington P, Harter P, Hein A, Heitz F, Hildebrandt MAT, Hillemanns P, Hogdall CK, Hogdall E, Hosono S, Jakubowska A, Jensen A, Ji BT, Karlan BY, Kelemen LE, Kellar M, Kiemeney LA, Krakstad C, Kjaer SK, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le ND, Lee AW, Lele S, Leminen A, Lester J, Levine DA, Liang D, Lim BK, Lissowska J, Lu K, Lubinski J, Lundvall L, Massuger LFAG, Matsuo K, Mcguire V, Mclaughlin JR, Mcneish I, Menon U, Milne RL, Modugno F, Moysich KB, Ness RB, Nevanlinna H, Eilber U, Odunsi K, Olson SH, Orlow I, Orsulic S, Weber RP, Paul J, Pearce CL, Pejovic T, Pelttari LM, Pike MC, Poole EM, Risch HA, Rosen B, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Rzepecka IK, Salvesen HB, Schernhammer E, Schwaab I, Shu XO, Shvetsov YB, Siddiqui N, Sieh W, Song H, Southey MC, Spiewankiewicz B, Sucheston L, Teo SH, Terry KL, Thompson PJ, Thomsen L, Tangen IL, Tworoger SS, Van Altena AM, Vierkant RA, Vergote I, Walsh CS, Wang-Gohrke S, Wentzensen N, Whittemore AS, Wicklund KG, Wilkens LR, Wu AH, Wu X, Woo YL, Yang H, Zheng W, Ziogas A, Hasmad HN, Berchuck A, Iversen ES, Schildkraut JM, Ramus SJ, Goode EL, Monteiro ANA, Gayther SA, Narod SA, Pharoah PP, Sellers TA, Phelan CM
Zeitschrift: PLoS ONE
Jahr der Veröffentlichung: 2015
Band: 10
Heftnummer: 6
Seitenbereich: e0128106
ISSN: 1932-6203


Abstract

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.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.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).These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.


FAU-Autoren / FAU-Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hein, Alexander PD Dr.
Frauenklinik


Autor(en) der externen Einrichtung(en)
Beatson West of Scotland Cancer Centre (BWSCC)
Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cancer Council Victoria
Cancer Research Initiatives Foundation (CARIF)
Cedars-Sinai Medical Center
Danish Cancer Society Research Center
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Friedrich-Schiller-Universität Jena
Glasgow Royal Infirmary (GRI)
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
H. Lee Moffitt Cancer Center & Research Institute
Institut für Humangenetik Wiesbaden
Kliniken Essen-Mitte
Kyushu University / 九州大学
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medical University of South Carolina (MUSC)
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
Public Health Ontario
Radboud university medical center / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC)
Radboud University Nijmegen
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Shanghai Cancer Institute / 上海市肿瘤研究所
Stanford University
Texas Southern University (TSU)
The University of Melbourne
University College London (UCL) (University of London)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of California Irvine
University of Cambridge
University of Copenhagen
University of Glasgow
University of Hawaii (U.H.)
University of Kansas (KU)
University of Malaya (UM) / Universiti Malaya
University of New Mexico
University of Pittsburgh
University of Southampton
University of Southern California (USC)
University of Texas MD Anderson Cancer Center
University of Toronto
University of Washington
Vanderbilt University


Zitierweisen

APA:
Chornokur, G., Lin, H.-Y., Tyrer, J.P., Lawrenson, K., Dennis, J., Amankwah, E.K.,... Phelan, C.M. (2015). Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk. PLoS ONE, 10(6), e0128106. https://dx.doi.org/10.1371/journal.pone.0128106

MLA:
Chornokur, Ganna, et al. "Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk." PLoS ONE 10.6 (2015): e0128106.

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Zuletzt aktualisiert 2018-09-10 um 07:26