Causal association between complement system FHR-5, CTRP9, and breast carcinoma in situ: a Mendelian randomization...

Area of Science:

• Genetics and Immunology
• Cancer Research
• Epidemiology

Background:

• Breast carcinoma in situ is a significant concern, yet its causes remain unclear, prompting treatment strategy debates.
• Understanding the etiology of breast carcinoma in situ is crucial for effective management.

Purpose of the Study:

• To explore potential causal associations between the complement system, complement C1q/tumor necrosis factor-related proteins (CTRPs), and breast carcinoma in situ using Mendelian randomization.
• To identify specific molecules within the complement system and CTRP family that may influence breast carcinoma in situ risk.

Main Methods:

• A two-sample multivariable Mendelian randomization (MR) study utilizing genome-wide association study (GWAS) data for complement factors and CTRPs.
• Analysis of summary-level statistics from breast carcinoma in situ GWAS data.
• Application of MR-Egger, inverse variance weighted (IVW), and weighted median methods, with sensitivity analyses including MR-Egger intercept, funnel plot, and leave-one-out analysis.

Main Results:

• Complement factor H-related protein 5 (FHR-5) was associated with a 67.2% increased risk of breast carcinoma in situ (IVW: OR 0.672, p < 0.05).
• CTRP9 was linked to a 57.0% increased risk of breast carcinoma in situ (IVW: OR 0.570, p < 0.05).
• No significant associations were found for other investigated molecules, suggesting context-specific relationships.

Conclusions:

• This MR study provides the first evidence of a direct link between FHR-5 and CTRP9 and susceptibility to breast carcinoma in situ.
• Further research into the roles of immunomodulatory molecules and immune responses in the tumor microenvironment is vital for managing breast carcinoma in situ.