Insights into modifiable risk factors of inflammatory disorders of breast: A univariable and multivariable Mendelian randomization study

Background: The causal relationship between modifiable risk factors and inflammatory disorders of the breast (IDB) remains unclear, posing a challenge to the early identification and intervention of patients with IDB. The present study aimed to clarify the causal association between 30 predominant risk factors and IDB. Methods: Single-variable MR (SVMR) and multi-variable MR (MVMR) analyses were used to investigate the causal association between 30 modifiable risk factors and IDB. Inverse-variance weighting (IVW), MR‒Egger, and weighted median (WM) were further supported by several sensitivity analyses. Results: Genetically predicted Adult BMI females, body fat percentage, trunk fat mass, Waist circumference, Overall health rating, Medication use (glucocorticoids), and smoking status were found to increase the risk of IDB (all P < 0.05). No significant association was detected between interleukin levels, autoimmune diseases, pregnancy, infection and IDB. Multivariate MR identified body fat percentage, and smoking status as risk factors for IDB. Conclusions: We are the first to use MR analysis to explore the causal relationships between modifiable risk factors and IDB, revealing smoking status and body fat percentage at the genetic level are causally associated with a higher risk of IDB.