Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits

Autor: Simon N. Stacey, Reynir Tómas Geirsson, Asgeir Thoroddsen, Gardar Sveinbjornsson, Gudny A. Arnadottir, Gisli Masson, Unnur Styrkarsdottir, Bjarni V. Halldorsson, Andres Ingason, Gudmar Thorleifsson, Anna Salvarsdottir, Patrick Sulem, Ragnheidur Arnadottir, Daniel F. Gudbjartsson, Vinicius Tragante, Jon G. Jonasson, Elisabet A. Helgadottir, Unnur Thorsteinsdottir, Karl Olafsson, Olafur B. Davidsson, Katrin Kristjansdottir, Michael L. Frigge, Ragnar P. Kristjansson, Thorunn Rafnar, Folkert W. Asselbergs, Valgerdur Steinthorsdottir, Florian Zink, Bjarni Gunnarsson, Gisli H. Halldorsson, Valur Gudmundsson, Lilja Stefansdottir, Jon K. Sigurdsson, Julius Gudmundsson, Olafur A. Stefansson, Orri Ingthorsson, Asmundur Oddsson, Kari Stefansson
Přispěvatelé: Læknadeild (HÍ), Faculty of Medicine (UI), School of Science and Engineering (RU), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Tækni- og verkfræðideild (HR), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Háskólinn í Reykjavík, Reykjavik University, Háskóli Íslands, University of Iceland
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
General Physics and Astronomy
Genome-wide association study
Identifies 2
Bioinformatics
Breast cancer
Brjóstakrabbamein
Genamengi
Beinþéttni
European Continental Ancestry Group/genetics
lcsh:Science
Non-U.S. Gov't
education.field_of_study
Multidisciplinary
Uterine leiomyoma
Leiomyoma
Research Support
Non-U.S. Gov't
Eitlar
musculoskeletal system
Leiomyoma/genetics
female genital diseases and pregnancy complications
3. Good health
surgical procedures
operative
Uterine Neoplasms
Steinefni
Female
Science
Population
Endometriosis
Biology
Research Support
White People
Article
General Biochemistry
Genetics and Molecular Biology
Sequence variants
03 medical and health sciences
Krabbameinsrannsóknir
medicine
Bone mineral density
Journal Article
Humans
Uterine Neoplasms/genetics
Hvítblæði
education
neoplasms
Genetic association
Krabbamein
Genome association
Risk loci
Telomere length
Case-control study
Cancer
General Chemistry
Epithelial ovarian cancer
medicine.disease
body regions
030104 developmental biology
Eggjastokkar
Case-Control Studies
lcsh:Q
Chronic lymphocytic leukemia
Susceptibility loci
Endometriosis/genetics
Genome-Wide Association Study
Meta-Analysis
Zdroj: Nature Communications, Vol 9, Iss 1, Pp 1-9 (2018)
Nature Communications, 9(1). Nature Publishing Group
Nature Communications
ISSN: 2041-1723
7837-8222
Popis: We thank the individuals who participated in the study and whose contribution made this work possible. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the cancer patients. T.R., B.G., P.S., B.V.H., G.T, and K.S. designed the study and interpreted the results. A.S, A.T., E.A.H., K.K., O.I., V.G., R.T.G., R.A., J.G.J., and K.O. carried out the subject ascertainment, recruitment, and collection of clinical data. U.S., V.S., S.N.S., J.G., G.A.A., A.O., F.Z., G.H., R.P.K., O.B.D., G.M., V.T., F.W.A., and U.T. collected, processed, and analyzed the genotype and phenotype data. O.A.S. performed the functional annotations. A.I., M.L.F., L.S., J.K.S., G.S., D.F.G., B.G., and B.V.H., performed the statistical and bioinformatics analyses. T.R., B.G., O.A.S, G.T., and K.S., drafted the manuscript. All authors contributed to the final version of the paper.
Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth.
This research has been conducted using the UK Biobank Resource under Application Number ‘24711’.
Databáze: OpenAIRE
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