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.
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.
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.
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.
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.
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Gene Expression
Gene–environment Interaction of GWAS Loci and Reproductive History in Uterine Fibroid Risk: A Case-control Study
14-Oct-2025