Uterine fibroids (UFs) are common hormone-dependent tumors with a complex etiology involving both genetic and environmental factors. This study aimed to investigate, for the first time, the associations between loci from genome-wide association studies (GWAS) and environmental risk factors in UF development, with a particular focus on gene–environment interactions.
Methods
DNA samples from 737 women with UF and 451 healthy controls were genotyped for ten UF-associated GWAS single nucleotide polymorphisms (SNPs) using probe-based polymerase chain reaction in this case-control study.
Results
SNP rs66998222 (LOC102723323, G/A) was associated with decreased UF risk in the total sample (odds ratio (OR) = 0.81, p = 0.038) and in patients with a history of induced abortion (OR = 0.70, p = 0.009). SNP rs11031731 (THEM7P, WT1, G/A) increased UF risk overall (OR = 1.39, p = 0.01), and in women with abortion history (OR = 1.60, p = 0.008) or without pelvic inflammatory disease (OR = 1.43, p = 0.02). SNPs rs641760 (PITPNM2, C/T) and rs2553772 (LOC105376626, G/T) showed protective effects depending on abortion history. SNP rs1986649 (FOXO1, C/T) was associated with later UF onset (p = 0.049) and slower growth (p = 0.017). GWAS loci influence UF-related genes involved in proliferation, inflammation, and hormone metabolism, underscoring their pathogenic role.
Conclusions
Our findings support a model in which environmental exposures, such as abortion and PID, modulate the penetrance and directionality of GWAS-identified UF loci. Some SNPs exhibit context-specific protective or deleterious effects, likely mediated through hormone-sensitive transcriptional programs and immune pathways. Future work should explore these interactions longitudinally and in multi-ethnic cohorts to inform personalized risk stratification.
Full text
https://xiahepublishing.com/1555-3884/GE-2025-00056
The study was recently published in the Gene Expression .
Gene Expression (GE) is an open-access journal. It was launched in 1991 by Chicago Medical School Press, and transferred to Cognizant Communication Corporation in 1994. From August 2022, GE is published by Xia & He Publishing Inc.
GE publishes peer-reviewed and high-quality original articles, reviews, editorials, commentaries, and opinions on its primary research topics including cell biology, molecular biology, genes, and genetics, especially on the cellular and molecular mechanisms of human diseases.
GE has been indexed in Medline (1991-2021), Scopus, Biological Abstracts, Biosis Previews, ProQuest, etc.
