The Mediating Role of Serum Phosphate in the BMI-Breast Cancer Association: A Prospective Study from the UK Biobank

Globally, breast cancer (BC) represents the most commonly diagnosed malignancy in women. This research explores the relationship between BC risk and both body mass index (BMI) classifications and serum phosphate concentrations, along with their possible interaction.

A total of 198,280 women from the UK Biobank were enrolled in this prospective cohort analysis, excluding those with prior or early tumor diagnoses to minimize reverse causality. BMI was categorized based on the standards established by the World Health Organization, and serum phosphate levels were measured at baseline. The associations among BMI, serum phosphate, and BC risk were evaluated using multivariable regression and mediation analyses, with adjustment for relevant confounding factors.

After controlling for confounding variables, multivariable linear regression revealed a significant negative correlation between BMI and serum phosphate levels (β = -3.120 × 10³, P < .0001). BMI showed a positive correlation with BC risk, whereas phosphate levels appeared to have a protective effect. Mediation analysis confirmed serum phosphate mediated 5.4% to 10.5% of the BMI-BC risk relationship, notably in overweight and obesity class I to II groups (P < .0001).

The study identified a nonlinear positive relationship between BMI and the risk of BC. peaking at moderate BMI levels. Serum phosphate was identified as a mediator that partially contributes to this association, providing novel insights into the metabolic pathways linking BMI to BC.