Meta-analysis and Mendelian randomisation study of IgA nephropathy and epithelial ovarian cancer risk
Authors: Liu Xiaolin , Wang Shan , Lv Hongwei , Chen Enli , Yu Jing 
Published: July 2024

Background
A potential association between a history of IgA nephropathy and the risk of epithelial ovarian cancer has been identified in clinical practice. However, it remains unclear whether a causal relationship exists between these two conditions. In this study, we employed both Mendelian randomisation and meta-analysis techniques to delve deeper into the genetic perspective on the association between a history of IgA nephropathy and the risk of epithelial ovarian cancer.
Objective
This study investigated the causal relationship between a history of IgA nephropathy and the risk of developing epithelial ovarian cancer.
Methods
Genome-Wide Association Study (GWAS) data from 15,587 IgA nephropathy patients of European ethnicity from different regions were utilized as the primary exposure. Additionally, GWAS data from patients with various subtypes of epithelial ovarian cancer, including high-grade and low-grade serous ovarian cancer, high-grade serous ovarian cancer, low-grade and low-malignant potential serous ovarian cancer, low-malignant potential serous ovarian cancer, low-grade serous ovarian cancer, and clear cell ovarian cancer, were included as study exposures. Causal effects were initially evaluated through inverse variance weighted (IVW), MR-Egger regression, and weighted median (WM) methods, followed by a multi-group univariate Mendelian randomisation analysis (UVMR). Sensitivity analysis was conducted using Cochran's Q test, MR-Egger regression intercept term, MR-PRESSO, and leave-one-out method to evaluate the stability and reliability of the results. Following the heterogeneity test results, a random-effects model was employed for the meta-analysis. Subsequently, subgroup analysis based on different pathology types was conducted using funnel plots to identify the source of heterogeneity. Publication bias was assessed using funnel plots and the Trim and Fill method.
Results
A genetically predicted history of IgA nephropathy showed a trend of decreasing incidence across different subtypes of epithelial ovarian cancer in the univariate Mendelian randomisation analysis (UVMR). However, statistical significance was not observed. Similarly, the results of the weighted median, simple mode, weighted mode, and MR-Egger analyses exhibited similar trends, with convincing positive results observed solely in the case of IgA nephropathy with high-grade serous. Specifically, a significant positive association was found in the UVMR of ovarian cancer (OR = 0.81, 95% CI = 0.75–0.87, p < 0.01). In this study, a random-effects model was utilized to conduct meta-analysis of the UVMR across multiple groups, revealing a statistically significant difference (OR = 0.89, 95% CI = 0.82–0.96, P < 0.01). The results of sensitivity analyses were consistent, suggesting that individuals with a history of IgA nephropathy had an 89% lower risk of developing epithelial ovarian carcinoma compared to controls. Subgroup analysis revealed a significant association between a history of IgA nephropathy and a reduced risk of serous ovarian cancer (OR = 0.89, 95% CI = 0.81–0.97, P < 0.01). However, this association was not statistically significant in the clear cell ovarian cancer subgroup, although a similar trend was observed (OR = 0.89, 95% CI = 0.71–1.12, P > 0.01).
Conclusion
The findings of this study indicate that individuals with a history of IgA nephropathy have a decreased risk of developing epithelial ovarian cancer, particularly serous epithelial ovarian cancer.