Journal article

Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility

M Earp, JP Tyrer, SJ Winham, HY Lin, G Chornokur, J Dennis, KKH Aben, H Anton-Culver, N Antonenkova, EV Bandera, YT Bean, MW Beckmann, L Bjorge, N Bogdanova, LA Brinton, A Brooks-Wilson, F Bruinsma, CH Bunker, R Butzow, IG Campbell Show all

Plos One | PUBLIC LIBRARY SCIENCE | Published : 2018

Abstract

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to..

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Grants

Awarded by European Commission


Funding Acknowledgements

The scientific development and funding for this project were funded by the following: NIH R01 CA-1491429 (Phelan PI); the US National Cancer Institute (R01-CA076016); the COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 HEALTH F2 2009-223175); the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112); the Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). Investigator-specific funding: G.C.-T. is supported by the National Health and Medical Research Council; B.K. is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; L.E.K. is supported by a Canadian Institute of Health Research New Investigator Award (MSH-87734). Funding of included studies: Funding of the constituent studies was provided by the California Cancer Research Program (00-01389V-20170, N01-CN25403, 2110200); the Canadian Institutes of Health Research (MOP-86727); Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124); the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy For Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L & S Milken Foundation; the Polish Ministry of Science and Higher Education (4 P05C 02814, 2 P05A 068 27); the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA095666, K07 CM 43047, K22-CA138563, N01-CN55424, N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P01-CA087969, CA072720, P50-CA105009, P50-CA136393, P30-R01CA014089, R01-CA016056, R01-CA017054, R01CA049449, R01-CA050385, R01-CA054419, R01CA058598, R01-CA058860, R01-CA061107, R01CA061132, R01-CA067262, R01-CA071766, R01CA074850, R01-CA080742, R01-CA080978, R01CA083918, R01-CA087538, R01-CA092044, 801095023, R01-CM 22443, R01-CA112523, R01CA114343, R01-CA126841, R01-CA136924, R03 CM 13148, R03-CM 15195, U01-CA069417, U01CA071966, UM1-CM 82910, UM 1-CM 86107 and Intramural research funds); the US Army Medical Research and Material Command (DAMD17-01-10729, DAMD17-02-1-0666, DAM D17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802); the US Public Health Service (PSA-042205); The National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01GB 9401); the State of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital "Womens Health Theme" and the Royal Marsden Hospital; WorkSafeBC.