Exploring the causal relationship between galectin levels and gynecologic cancers: A Mendelian randomization study
Introduction
Gynecologic cancers, including ovarian, endometrial, and cervical cancers, pose a significant global health burden, affecting women worldwide. Despite advancements in screening, diagnosis, and treatment, the prognosis for patients with advanced-stage gynecologic cancers remains poor. Therefore, identifying novel biomarkers and understanding the underlying molecular mechanisms are crucial for improving early detection, prognosis, and therapeutic strategies. Galectins, a family of β-galactoside-binding proteins, have been implicated in various pathological processes, including tumorigenesis, immune evasion, and metastasis. This study aims to investigate the causal relationship between galectin levels and the risk of gynecologic cancers using Mendelian randomization (MR) analysis.
Methods
The study utilized data on galectin levels (Gal-1, Gal-2, Gal-3, Gal-4, Gal-7, Gal-8, Gal-9, and Gal-10) from the IEU Open genome-wide association study (GWAS) project. Gynecologic cancer data was sourced from the GWAS project, Ovarian Cancer Association Consortium (OCAC), and FinnGen consortium. A two-sample MR analysis was conducted to explore the causal relationship between galectin levels and gynecologic cancers. Bi-directional MR analysis was also performed to examine the direction of causality.
Results
The study found significant associations between galectin levels and the incidence of gynecologic cancers. For example, elevated Gal-1 levels were linked to higher incidences of ovarian cancer, particularly high-grade serous and invasive mucinous subtypes. Gal-2 and Gal-4 levels were associated with a reduced risk of malignant neoplasm of corpus uteri and endometrial cancer. Gal-3 and Gal-8 levels showed a potential association with cervical cancer, although further research is needed to establish causality.
Discussion
This study highlights the potential causal relationships between galectin levels and gynecologic cancers. The findings provide novel insights into the molecular mechanisms underlying gynecologic cancer development and emphasize the importance of galectins as potential biomarkers or therapeutic targets. However, the study has limitations, including the use of data from individuals of European ancestry and the lack of individual-level data, which may impact the generalizability of the findings.
Conclusion
Further experimental and clinical validation is required to confirm the causal relationships and explore the underlying biological mechanisms. If validated, galectins could serve as promising biomarkers or therapeutic targets in gynecologic oncology.
