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Type 1 Diabetes and Breast Cancer Risk: Evidence From an Updated Meta‐Analysis and Mendelian Randomization Study

Year: 2026

Type: article

Abstract: Background It remains uncertain whether Type 1 diabetes (T1D) is linked to the risk of breast cancer (BC), with previous epidemiological findings yielding inconsistent conclusions. Methods This study combined evidence from observational research through meta‐analysis and used a two‐sample Mendelian randomization (MR) framework to assess whether T1D contributes causally to BC risk. A total of five eligible articles encompassing nine cohort studies were included in the meta‐analysis. Genetic variants with strong associations to T1D were sourced from the IEU Open GWAS database (GWAS ID: ebi‐a‐GCST90018925). Summary‐level data for BC and its estrogen receptor (ER) subtypes were obtained from the FinnGen consortium (release R12). Results The pooled meta‐analysis showed a statistically significant inverse association between T1D and BC risk (pooled relative effect estimate = 0.91, 95% CI: 0.85–0.98, p = 0.01). MR analyses provided evidence consistent with an inverse association between genetically predicted T1D and overall BC risk (IVW HR = 0.96, 95% CI: 0.92–1.00, p = 0.033), with a similar inverse association observed for ER‐positive BC (IVW HR = 0.95, 95% CI: 0.92–0.99, p = 0.013), whereas no statistically significant association was observed for ER‐negative BC. Sensitivity analyses indicated stable effect estimates despite evidence of horizontal pleiotropy detected by MR‐PRESSO, while the MR‐Egger intercept showed no evidence of directional pleiotropy. Conclusion The combined observational and genetic evidence is consistent with a possible inverse association between T1D and BC risk, particularly for ER‐positive disease, whereas no significant association was observed for ER‐negative BC. Further studies are warranted to confirm these findings and clarify the underlying mechanisms.

Source: International Journal of Endocrinology

DOI: 10.1155/ije/2837214