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

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Authors
Rafnar, Thorunn
Gunnarsson, Bjarni
Stefansson, Olafur A
Sulem, Patrick
Ingason, Andres
Frigge, Michael L
Stefansdottir, Lilja
Sigurdsson, Jon K
Tragante, Vinicius
Steinthorsdottir, Valgerdur
Styrkarsdottir, Unnur
Stacey, Simon N
Gudmundsson, Julius
Arnadottir, Gudny A
Oddsson, Asmundur
Zink, Florian
Halldorsson, Gisli
Sveinbjornsson, Gardar
Kristjansson, Ragnar P
Davidsson, Olafur B
Salvarsdottir, Anna
Thoroddsen, Asgeir
Helgadottir, Elisabet A
Kristjansdottir, Katrin
Ingthorsson, Orri
Gudmundsson, Valur
Geirsson, Reynir T
Arnadottir, Ragnheidur
Gudbjartsson, Daniel F
Masson, Gisli
Asselbergs, Folkert W
Jonasson, Jon G
Olafsson, Karl
Thorsteinsdottir, Unnur
Halldorsson, Bjarni V
Thorleifsson, Gudmar
Stefansson, Kari
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Issue Date
2018-09-07

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Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits. 2018, 9 (1): 3636 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.
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https://www.nature.com/articles/s41467-018-05428-6
ae974a485f413a2113503eed53cd6c53
10.1038/s41467-018-05428-6
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