Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study

Journal article


Publication Details

Author(s): Lee AW, Tyrer JP, Doherty JA, Stram DA, Kupryjanczyk J, Dansonka-Mieszkowska A, Plisiecka-Halasa J, Spiewankiewicz B, Myers EJ, Chenevix-Trench G, Fasching PA, Beckmann M, Ekici AB, Hein A, Vergote I, Van Nieuwenhuysen E, Lambrechts D, Wicklund KG, Eilber U, Wang-Gohrke S, Chang-Claude J, Rudolph A, Sucheston-Campbell L, Odunsi K, Moysich KB, Shvetsov YB, Thompson PJ, Goodman MT, Wilkens LR, Doerk T, Hillemanns P, Duerst M, Runnebaum IB, Bogdanova N, Pelttari LM, Nevanlinna H, Leminen A, Edwards RP, Kelley JL, Harter P, Schwaab I, Heitz F, Du Bois A, Orsulic S, Lester J, Walsh C, Karlan BY, Hogdall E, Kjaer SK, Jensen A, Vierkant RA, Cunningham JM, Goode EL, Fridley BL, Southey MC, Giles GG, Bruinsma F, Wu X, Hildebrandt MAT, Lu K, Liang D, Bisogna M, Levine DA, Weber RP, Schildkraut JM, Iversen ES, Berchuck A, Terry KL, Cramer DW, Tworoger SS, Poole EM, Olson SH, Orlow I, Bandera EV, Bjorge L, Tangen IL, Salvesen HB, Krakstad C, Massuger LFAG, Kiemeney LA, Aben KKH, Van Altena AM, Bean Y, Pejovic T, Kellar M, Le ND, Cook LS, Kelemen LE, Brooks-Wilson A, Lubinski J, Gronwald J, Cybulski C, Jakubowska A, Wentzensen N, Brinton LA, Lissowska J, Yang H, Nedergaard L, Lundvall L, Hogdall C, Song H, Campbell IG, Eccles D, Glasspool R, Siddiqui N, Carty K, Paul J, Mcneish LA, Sieh W, Mcguire V, Rothstein JH, Whittemore AS, Mclaughlin JR, Risch HA, Phelan CM, Anton-Culver H, Ziogas A, Menon U, Ramus SJ, Gentry-Maharaj A, Harrington P, Pike MC, Modugno F, Rossing MA, Ness RB, Pharoah PDP, Stram DO, Wu AH, Pearce CL
Journal: Gynecologic Oncology
Publication year: 2015
Volume: 136
Journal issue: 3
Pages range: 542-8
ISSN: 0090-8258


Abstract

Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted.Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations.We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p=0.045, mucinous), LHCGR (p=0.046, high-grade serous), GNRH (p=0.041, high-grade serous), and FSHB (p=0.036, overall invasive). There was also suggestive evidence for INHA (p=0.060, overall invasive).Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available.


FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Hein, Alexander PD Dr.
Frauenklinik


External institutions with authors

Alberta Health Services (AHS)
Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cancer Council Victoria
Cedars-Sinai Medical Center
Danish Cancer Society
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fred Hutchinson Cancer Research Center
Friedrich-Schiller-Universität Jena
Glasgow Royal Infirmary (GRI)
Harvard University
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
H. Lee Moffitt Cancer Center & Research Institute
Institute for Oncology Ljubljana (OIL)
Institut für Humangenetik Wiesbaden
Kliniken Essen-Mitte
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Memorial Sloan Kettering Cancer Center
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
Oregon Health and Science University (OSHU)
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
Princess Anne Hospital
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Stanford University
Texas Southern University (TSU)
The University of Melbourne
Universität Ulm
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of California Irvine
University of California Los Angeles (UCLA)
University of Cambridge
University of Copenhagen
University of Glasgow
University of Hawaii (U.H.)
University of Kansas (KU)
University of New Mexico
University of Pittsburgh
University of Southern California (USC)
University of Texas MD Anderson Cancer Center


How to cite

APA:
Lee, A.W., Tyrer, J.P., Doherty, J.A., Stram, D.A., Kupryjanczyk, J., Dansonka-Mieszkowska, A.,... Pearce, C.L. (2015). Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study. Gynecologic Oncology, 136(3), 542-8. https://dx.doi.org/10.1016/j.ygyno.2014.12.017

MLA:
Lee, Alice W., et al. "Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study." Gynecologic Oncology 136.3 (2015): 542-8.

BibTeX: 

Last updated on 2018-06-10 at 02:26