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

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


Title: Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits
Author: Rafnar, Thorunn
Bjarni Gunnarsson
Ólafur A. Stefánsson
Sulem, Patrick   orcid.org/0000-0001-7123-6123
Ingason, Andrés
Frigge, Michael L.
Lilja Stefánsdóttir
Jón K. Sigurðsson
Tragante, Vinicius
Steinthorsdottir, Valgerdur   orcid.org/0000-0003-1846-6274
... 27 more authors Show all authors
Date: 2018-09-07
Language: English
Scope: 3636
University/Institute: Háskólinn í Reykjavík
Reykjavik University
Háskóli Íslands
University of Iceland
School: 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)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Nature Communications;9(1)
ISSN: 2041-1723 (eISSN)
DOI: 10.1038/s41467-018-05428-6
Subject: Genome association; Chronic lymphocytic leukemia; Epithelial ovarian cancer; Bone mineral density; Susceptibility loci; Breast cancer; Risk loci; Sequence variants; Telomere length; Identifies 2; Genamengi; Hvítblæði; Eitlar; Krabbamein; Eggjastokkar; Beinþéttni; Steinefni; Brjóstakrabbamein; Krabbameinsrannsóknir
URI: https://hdl.handle.net/20.500.11815/1328

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Citation:

Rafnar, T., Gunnarsson, B., Stefansson, O.A. et al. Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits. Nat Commun 9, 3636 (2018) doi:10.1038/s41467-018-05428-6

Abstract:

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.

Description:

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.

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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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