Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 30226466.
- Also identified by DOI 10.7554/eLife.37110 and PMC identifier 6203434.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>TERT, TERC, OBFC1</i> - highlighting the role of telomere maintenance - <i>TP53</i> and <i>ATM</i>. Genes involved in genitourinary development, <i>WNT4, WT1, SALL1, MED12, ESR1, GREB1, FOXO1, DMRT1</i> and uterine stem cell marker antigen <i>CD44,</i> formed another strong subgroup. The combined risk contributed by the 22 loci was associated with <i>MED12</i> 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.
Medical subject headings
- Genetic Loci
- Genetic Predisposition to Disease
- Genomic Instability
- Leiomyoma
- Uterine Neoplasms