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

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 P, 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 (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 10

Pages Range: e0128106

Journal Issue: 6

DOI: 10.1371/journal.pone.0128106

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.

Authors with CRIS profile

Involved external institutions

University of Cambridge United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Cedars-Sinai Medical Center United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Cancer Council Victoria Australia (AU) University College London (UCL) United Kingdom (GB) Kliniken Essen-Mitte Germany (DE) Memorial Sloan Kettering Cancer Center United States (USA) (US) Duke University United States (USA) (US) Cancer Research Initiatives Foundation (CARIF) / Cancer Research Malaysia (CRM) Malaysia (MY) University of California Irvine United States (USA) (US) Vanderbilt University United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) University of Malaya (UM) / Universiti Malaya Malaysia (MY) University of Texas MD Anderson Cancer Center United States (USA) (US) University of Southern California (USC) United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) University of Toronto Canada (CA) Mayo Clinic United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) University of Pittsburgh United States (USA) (US) University of Glasgow United Kingdom (GB) Public Health Ontario Canada (CA) Stanford University United States (USA) (US) Kyushu University / 九州大学 Japan (JP) Radboud University Nijmegen Netherlands (NL) University of Copenhagen Denmark (DK) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Texas Southern University (TSU) United States (USA) (US) British Columbia Cancer Agency Canada (CA) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) Danish Cancer Society Research Center Denmark (DK) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) Oregon Health and Science University (OSHU) United States (USA) (US) Medical University of South Carolina (MUSC) United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Shanghai Cancer Institute / 上海市肿瘤研究所 China (CN) University of Kansas (KU) United States (USA) (US) University of Southampton United Kingdom (GB) Friedrich-Schiller-Universität Jena Germany (DE) Brigham and Women's Hospital (BWH) United States (USA) (US) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Glasgow Royal Infirmary (GRI) United Kingdom (GB) Peter MacCallum Cancer Centre Australia (AU) Rutgers Cancer Institute of New Jersey United States (USA) (US) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) University of Washington United States (USA) (US) The University of Melbourne Australia (AU) Institut für Humangenetik Wiesbaden Germany (DE) Yale University United States (USA) (US)

How to cite

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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