The relationship between infectious pathogen antibodies, plasma metabolites, and breast cancer: A Mendelian randomization study with mediation analysis

Breast cancer (BC) has the second highest incidence rate among women worldwide. Although there are various treatment methods, the prognosis is poor once metastasis occurs. However, the extent to which pathogens of infectious diseases influence the risk of BC remains unclear. The goal of this study is to determine if these pathogens are causally related to BC development. A Mendelian randomization (MR) analysis is used to assess the causal relationship between infectious pathogen antibodies and the risk of BC, as well as their potential intermediary factors. Two-sample MR analysis using inverse variance weighting (IVW) is conducted to determine the causal relationship between infectious pathogen antibodies and the risk of BC. Additionally, the mediating role of 1400 metabolites between infectious pathogen antibodies and the risk of BC is analyzed. There were 5 infectious pathogen antibodies and 86 metabolites associated with BC (P < .05). There were 14 metabolites that mediated the pathway between infectious pathogen antibodies and BC. X-07765 levels showed a significant negative mediating effect on the relationship between Anti-human herpes virus 6 IgG seropositivity and BC (beta = -0.0025, 95% CI [-0.0046, -0.0003], P = .0236), accounting for 14.8% of the effect (95% CI: 27.7-1.99). This study provides a thorough evaluation of the causal relationships among infectious pathogen antibodies, plasma metabolites, and BC. Our research has identified 5 infectious pathogen antibodies that exhibit a causal relationship with BC, mediated through 86 distinct metabolites.