NDLI: Association between gynecological cancers and female infertility: insights from bidirectional Mendelian randomization analysis

Content Provider	Springer Nature : BioMed Central
Author	Li, Jifeng Zeng, Yifei Zhang, Dongxiao
Abstract	Purpose In recent years, research interest in the potential link between female infertility (FI) and gynecological cancer (GC), including ovarian cancer (OC), endometrial cancer (EC), cervical cancer (CC), and breast cancer (BC), has grown, yet findings remain inconclusive. This study aims to explore the causal relationship between FI and GC using bidirectional two-sample Mendelian randomization (MR) analyses, thereby informing future strategies for FI and GC prevention. Methods We utilized SNPs identified from genome-wide association studies (GWAS) on FI and GC. The inverse variance weighted (IVW) method served as the primary approach to assess the causal association between FI and GC. Additionally, five other MR methods—Weighted median, Weighted mode, MR-Egger, Simple mode, and Robust-Adjusted Profile Score—were employed to enhance result robustness and credibility. Results In the forward MR analysis, our IVW results indicated no significant association between FI and GC (FI-BC: OR = 0.95, 95% CI: 0.83–1.09, P = 0.47, P-FDR = 0.775; FI-OC: OR = 1.01, 95% CI: 0.84–1.24, P = 0.789, P-FDR = 0.896; FI-CC: OR = 0.80, 95% CI: 0.61–1.06, P = 0.118, P-FDR = 0.775; FI-EC: OR = 1.07, 95% CI: 0.88–1.30, P = 0.490, P-FDR = 0.775).In the reverse MR analysis, we found a marginal association between BC and FI. However, after adjusting for multiple testing using the FDR method, no significant causal relationship was found between BC and FI, suggesting a marginal association (OR = 1.054, 95% CI: 1.001–1.108, P = 0.043, P-FDR = 0.331). For other cancers, no significant causal relationships were observed between OC, CC and EC with FI(OC-FI: OR = 1.043, 95% CI: 0.999–1.087, P = 0.051, P-FDR = 0.331;CC-FI: OR = 0.992, 95% CI: 0.956–1.028, P = 0.654, P-FDR = 0.836; EC-FI: OR = 1.006, 95% CI: 0.956–1.055, P = 0.809, P-FDR = 0.885). Conclusions Our study found no significant causal relationship between FI and GC. However, a potential marginal association between BC and FI was observed. These findings underscore the need for further research to confirm this association and emphasize the importance of reproductive protection for young breast cancer patients to preserve fertility.
Related Links	https://bmcwomenshealth.biomedcentral.com/counter/pdf/10.1186/s12905-025-03729-9.pdf
Ending Page	8
Page Count	8
Starting Page	1
File Format	HTM / HTML
ISSN	14726874
DOI	10.1186/s12905-025-03729-9
Journal	BMC Women's Health
Issue Number	1
Volume Number	25
Language	English
Publisher	BioMed Central
Publisher Date	2025-04-18
Access Restriction	Open
Subject Keyword	Gynecology Maternal and Child Health Reproductive Medicine Mendelian randomization Female infertility Gynecological cancer Ovarian cancer Endometrial cancer Cervical cancer Breast cancer
Content Type	Text
Resource Type	Article
Subject	Obstetrics and Gynecology Reproductive Medicine
Journal Impact Factor	2.4/2023
5-Year Journal Impact Factor	2.9/2023

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