Exploring the genetic correlation and causal relationships between breast cancer and meningioma using bidirectional Mendelian randomization

Feb 5, 2025Scientific reports

Genetic links and possible causes between breast cancer and meningioma using two-way genetic analysis

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Abstract

Genetically predicted overall breast cancer (: 1.17, P = 0.0045) is associated with a potential causal relationship with intracranial meningioma.

A significant association was observed between overall breast cancer and intracranial meningioma, particularly for estrogen receptor-positive breast cancer (OR: 1.21, P = 0.0006).
No causal relationships were identified between intracranial meningioma and three breast cancer subtypes, nor between spinal meningioma and any breast cancer subtype.
Linkage disequilibrium score regression indicated a modest positive genetic correlation between overall breast cancer and intracranial meningioma (rg: 0.152, P = 0.048).
Shared risk genes PITPNB, TTC28, and CHEK2 were identified among overall breast cancer, estrogen receptor-positive breast cancer, and intracranial meningioma.
ER-related signaling pathways and DNA damage regulation may be important in the development of both breast cancer and intracranial meningioma.

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Previous studies have indicated a significantly higher prevalence of breast cancer (BC) among female patients with meningioma compared to the general female population. Therefore, this study aimed to assess the causal relationship between BC and meningioma at the genetic level. Genetic instrumental variables (IVs) for BC were identified from the Breast Cancer Association Consortium (BCAC), the Discovery Biology and Risk of Inherited Variants in Breast Cancer Consortium (DRIVE), the Collaborative Oncological Gene-environment Study (iCOGS), and 11 other BC genome-wide association studies (). Meningioma GWAS data were obtained from the FinnGen consortium and were further divided into intracranial and spinal meningioma groups for analysis. The primary analysis employed the inverse-variance weighted (IVW) method, supported by sensitivity analysis to address pleiotropy and enhance robustness. Next, linkage disequilibrium score regression (LDSC) was used to assess the genetic correlation between BC and meningioma. Finally, we applied the Functional Mapping and Annotation (FUMA) platform to conduct an in-depth analysis of the GWAS data. After rigorous screening and (MR) tests, genetically predicted overall BC (: 1.17, P = 0.0045) and ER(estrogen receptors) + BC (OR: 1.21, P = 0.0006) showed a potential causal association with intracranial meningioma. No causal relationships were found between intracranial meningioma and three BC subtypes. No bidirectional causal relationships were found between spinal meningioma and any BC subtype. The LDSC results suggested a modest positive genetic correlation between overall BC (rg: 0.152, SE: 0.077, P = 0.048), ER + BC (rg: 0.181, SE: 0.086, P = 0.035), and intracranial meningioma. FUMA analysis identified PITPNB, TTC28, and CHEK2 as shared risk genes between overall BC, ER + BC, and intracranial meningioma. These findings suggest that BC, especially ER + BC, may be a risk factor for intracranial meningioma. ER-related signaling pathways and the regulation of DNA damage may play a critical role in the pathogenesis of both diseases.

Key numbers

1.17

Causal Association with Intracranial Meningioma (Overall BC)

for genetically predicted overall BC

1.21

Causal Association with Intracranial Meningioma (ER+ BC)

for genetically predicted ER+ BC

0.152

Genetic Correlation between Overall BC and Intracranial Meningioma

Genetic correlation coefficient

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Exploring the genetic correlation and causal relationships between breast cancer and meningioma using bidirectional Mendelian randomization

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