rs7907606 — STN1

Uterine fibroids (leiomyomas) are benign smooth muscle tumors of the uterus that affect up to 70–80% of women by age 50, causing heavy menstrual bleeding, pelvic pain, and in some cases impaired fertility. Their growth is driven by complex interactions between hormones, genomic instability, and abnormal cell proliferation. rs7907606 is an intergenic variant sitting between two genes with compelling biological relevance to fibroid formation: STN1 (also called OBFC1)¹¹ STN1 (also called OBFC1)
STN1 is a subunit of the CST complex (CTC1-STN1-TEN1) that protects telomere ends and coordinates telomere replication with DNA polymerase alpha-primase and SLK²² SLK
SLK is a serine/threonine kinase involved in cytoskeletal organization, focal adhesion assembly, actin polymerization, and cell migration. Multiple independent GWAS have pinpointed this locus as a reproducible fibroid susceptibility region.

The variant is intergenic — it does not alter a protein directly — and its functional effect appears to be regulatory: it likely modulates the expression of STN1, SLK, or both in uterine tissue. A 2019 trans-ethnic GWAS found that genetically-predicted expression of OBFC1 in esophageal mucosa (a proxy tissue) was significantly associated with fibroid risk³³ A 2019 trans-ethnic GWAS found that genetically-predicted expression of OBFC1 in esophageal mucosa (a proxy tissue) was significantly associated with fibroid risk
P=8.7×10⁻⁸, from Edwards et al. 2019, supporting a gene-expression mechanism rather than a protein-coding one.

Two biological pathways connect these genes to fibroid development. First, the STN1/CST complex maintains telomere integrity — and telomere length itself has a documented causal role in fibroid risk⁴⁴ documented causal role in fibroid risk
Mendelian randomization: genetically longer telomeres increase leiomyoma risk OR=1.73, p=4.9×10⁻¹⁶. Longer telomeres enable smooth muscle cells to undergo more rounds of replication before senescence, which may allow pre-malignant or hormonally dysregulated cells to accumulate the additional mutations required for fibroid initiation. Second, SLK controls cytoskeletal dynamics and focal adhesion assembly — processes that govern how smooth muscle cells attach to the extracellular matrix and migrate within the myometrium. Altered SLK activity could promote the aberrant proliferation and tissue remodeling that characterizes fibroid growth.

The fibroid association at this locus has been replicated across multiple large independent studies. Rafnar et al. (2018) performed a meta-analysis in 16,595 European cases and 523,330 controls⁵⁵ Rafnar et al. (2018) performed a meta-analysis in 16,595 European cases and 523,330 controls
Nature Communications and identified rs7907606 at the OBFC1/STN1 locus as one of 21 variants at 16 genome-wide significant loci, with OR 1.10 (p=3×10⁻⁹). The paper noted that several fibroid loci — including this one — overlapped with loci for other tumors, suggesting shared cancer-related biology. Edwards et al. (2019) extended this work in a trans-ethnic cohort of 21,804 cases⁶⁶ Edwards et al. (2019) extended this work in a trans-ethnic cohort of 21,804 cases
combining eMERGE network data with UK Biobank and confirmed the OBFC1 locus with even stronger evidence (p=2×10⁻¹⁶, OR 1.12, 95% CI 1.09–1.15).

At the clinical level, Ponomareva et al. (2024) genotyped 737 fibroid patients and 451 controls in Russia⁷⁷ Ponomareva et al. (2024) genotyped 737 fibroid patients and 451 controls in Russia
Front Biosci Schol Ed and found an OR of 1.34 (95% CI 1.03–1.74, p=0.028) in women without prior pelvic inflammatory disease — suggesting that infection-related inflammation may mask the genotype effect in women with PID history. Notably, this study identified a significant gene-gene interaction between rs7907606 and rs547025 in SIRT3 (a mitochondrial deacetylase involved in oxidative stress response), which together contributed the most information to fibroid risk entropy of any variant pair tested. This interaction hints at a combined telomere/oxidative stress axis in fibroid susceptibility.

Population frequencies are notably higher in women of African ancestry (G allele ~49%) than in European (16%) or East Asian (18%) populations. This disparity is clinically relevant: African American women have 2–3 times higher fibroid incidence and more severe disease than European American women, and genetic factors at loci like this one may contribute to that disparity.

This is a GWAS susceptibility locus with a moderate effect size (OR 1.10–1.34 per copy), not a deterministic mutation. Having one or two copies of the G allele increases risk but does not cause fibroids. The clinical relevance lies in knowing your risk profile to guide appropriate surveillance — specifically, earlier or more frequent pelvic ultrasound screening for women who are symptomatic or have a family history of fibroids.

Symptom awareness matters: heavy menstrual bleeding, pelvic pressure or pain, frequent urination, or pain during intercourse are common fibroid symptoms that warrant evaluation. Many fibroids are asymptomatic and require no intervention; symptomatic cases have multiple treatment options ranging from medication to minimally invasive procedures.

The interaction with SIRT3 (mitochondrial antioxidant regulation) suggests that oxidative stress management — particularly relevant if you also carry risk variants in oxidative stress pathways — may be biologically meaningful context, though direct intervention evidence for this locus is not yet established.

rs547025 (SIRT3): The strongest gene-gene interaction in fibroid risk identified by Ponomareva et al. (2024) was between rs7907606 and rs547025 in SIRT3, a mitochondrial deacetylase that regulates oxidative phosphorylation and reactive oxygen species production. The combined effect was the largest single pairwise contributor to fibroid risk entropy in that study. The biological model: telomere maintenance stress (STN1/SLK locus) combined with impaired mitochondrial antioxidant activity (SIRT3) may create a permissive cellular environment for fibroid initiation.

rs12696304 (TERC): The TERC locus (telomerase RNA component) directly regulates telomere length. Women who carry risk alleles at both the STN1 locus (rs7907606) and the TERC locus (rs12696304-G) may have additive effects on telomere biology, potentially amplifying the shared causal pathway (longer functional telomere length → greater fibroid susceptibility) identified in the Mendelian randomization data.