Inflammatory Proteins Mediate the Causal Association between Sleep Traits and Breast Cancer: A Mendelian...

Area of Science:

• Genetics and Epidemiology
• Cancer Research
• Sleep Science

Background:

• Breast cancer (BC) is a leading cancer in women, influenced by genetic, environmental, and lifestyle factors.
• The causal relationship between modifiable sleep behaviors and BC risk is not well understood.

Purpose of the Study:

• To investigate the causal impact of sleep phenotypes on overall BC and its subtypes using Mendelian randomization (MR).
• To explore the mediating role of inflammatory proteins in the relationship between sleep and BC.

Main Methods:

• Two-sample Mendelian randomization (MR) was employed, with inverse-variance weighted (IVW) as the primary analysis.
• Sensitivity analyses and reverse-MR were conducted for robustness.
• A two-step MR design was used to quantify mediation effects.

Main Results:

• Morning chronotype was associated with reduced risk for overall BC and luminal A BC.
• Short sleep duration correlated with decreased risk for overall BC and luminal A BC.
• Long sleep duration was linked to increased risk for triple-negative BC and luminal A BC.
• CXCL11 was identified as a mediator, explaining 22.4% of the causal effect of short sleep on luminal A BC.

Conclusions:

• Morning chronotype appears protective against BC.
• Prolonged sleep duration is associated with elevated risk for triple-negative and luminal A BC subtypes.
• CXCL11 plays a partial mediating role in the protective effect of short sleep on luminal A BC.
• Findings support sleep optimization as a BC prevention strategy.