| Title: | Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability |
| Journal: | eLife |
| Published: | 18 Sep 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30226466/ |
| DOI: | https://doi.org/10.7554/elife.37110 |
Publication 8567
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Abstract
Uterine leiomyomas (ULs) are benign tumors that are a major burden to women's health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics. 22 loci displayed a genome-wide significant association. The likely predisposition genes could be grouped to two biological processes. Genes involved in genome stability were represented by TERT, TERC, OBFC1 - highlighting the role of telomere maintenance - TP53 and ATM. Genes involved in genitourinary development, WNT4, WT1, SALL1, MED12, ESR1, GREB1, FOXO1, DMRT1 and uterine stem cell marker antigen CD44, formed another strong subgroup. The combined risk contributed by the 22 loci was associated with MED12 mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis, and in part explain the more frequent occurrence of UL in women of African origin.</p>
18 Authors
- Niko Välimäki
- Heli Kuisma
- Annukka Pasanen
- Oskari Heikinheimo
- Jari Sjöberg
- Ralf Bützow
- Nanna Sarvilinna
- Hanna-Riikka Heinonen
- Jaana Tolvanen
- Simona Bramante
- Tomas Tanskanen
- Juha Auvinen
- Outi Uimari
- Amjad Alkodsi
- Rainer Lehtonen
- Eevi Kaasinen
- Kimmo Palin
- Lauri A Aaltonen
1 Application
| Application ID | Title |
|---|---|
| 32506 | Genome Wide Association Studies of Colorectal Cancer, Uterine Leiomyoma and Other Tumor Types |
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