Mendelian randomization and transcriptomic data analysis reveals the causal association between gout and breast cancer

The association between gout and cancer risk has garnered significant interest, particularly in relation to breast cancer, which is the most prevalent cancer among women globally. Nevertheless, the coincidental link between gout and breast cancer, along with its underlying pathogenesis, remains inadequately elucidated. This study utilized publicly available genome-wide association study data from individuals of European ancestry, with sample sizes drawn from multiple genome-wide association study studies, covering genetic variations related to gout and breast cancer. Additionally, transcriptomic data analysis was conducted using datasets from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases, with the TCGA database comprising 199 adjacent normal tissue samples and 1085 breast cancer tissue samples. Following a rigorous sequence of quality control procedures, we incorporated suitable instrumental variables that exhibited significant associations with the exposure (gout). Five algorithms, namely Mendelian randomization (MR) Egger, weighted median, inverse variance weighting, simple mode, and weighted mode, were employed to deduce the causal link between gout and breast cancer. Moreover, we evaluated the reliability of the MR analysis through heterogeneity and pleiotropy assessments. Subsequently, transcriptomic data analysis was conducted utilizing TCGA and Gene Expression Omnibus databases to explore the possible correlation between gout and breast cancer. MR analysis revealed a stochastic relationship between genetic predisposition to gout and a decreased risk of breast cancer in individuals of European descent (odds ratio: 0.83, 95% CI: 0.71-0.98, P = .031). Additionally, the sensitivity analysis underscored the strength and reliability of the present MR findings. A key gene (MLX interacting protein-like) was identified using lasso regression methods. The gene showed a strong predictive performance in survival prediction (P < .05). Our MR study offers evidence indicating that genetic variations linked to gout are causally correlated with a decreased risk of breast cancer in the European population. Furthermore, transcriptomic data analysis indicates that the key gout-associated gene, MLX interacting protein-like, is implicated and holds predictive significance in the pathogenesis of breast cancer.