An Updated Meta-Analysis on Serum Vitamin D Levels and the Risk of Breast Cancer: Vitamin D Levels and Breast Cancer Risk

Background: Although numerous observational studies suggest that higher vitamin D levels are associated with a reduced risk of breast cancer, the overall evidence remains inconclusive. This study aimed to comprehensively evaluate this association through a systematic review and meta-analysis.Methods: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar up to February 16, 2024. Relevant articles were extracted, and title and abstract screening followed by full-text screening was carried out. Quality assessment was followed by data extraction and analysis for selected articles. All pooled analyses were performed on the natural log scale and exponentiated to obtain valid odds ratios (ORs).Results: Nineteen case-control studies, comprising 12 541 cases and 29 272 controls, were included. Lower circulating vitamin D levels were significantly associated with an increased risk of breast cancer (OR, 1.70; 95% CI, 1.31–2.23; P < .001). Between-study heterogeneity was high (I2 = 96.4%). In a prespecified subgroup analysis by study design, nested case-control studies showed a modest but statistically significant increase in risk (OR, 1.20; 95% CI, 1.06–1.36; I2 = 0.0%), whereas retrospective studies showed a larger but highly heterogeneous increase in risk (OR, 2.06; 95% CI, 1.38–3.08; I2 = 98.1%).Conclusions: This meta-analysis, using a harmonized log-scale approach, supports a significant inverse association between vitamin D levels and breast cancer risk. The most reliable evidence from nested case-control studies suggests a modest increase in risk, while retrospective studies likely overestimate the association due to reverse causality. Further well-designed prospective studies are warranted.