Type 1 Diabetes and Breast Cancer Risk: Evidence From an Updated Meta-Analysis and Mendelian Randomization Study.
4 affiliations
- 1Medical Education Center of Jinan University Jinan University Guangzhou China jnu.edu.cn.
- 2Department of Breast Jiangmen Central Hospital Jiangmen China bjch.com.
- 3Department of Thyroid and Breast Surgery Guangzhou First People's Hospital Guangzhou China gzhosp.cn.
- 4School of Medicine South China University of Technology Guangzhou China scut.edu.cn.
Abstract
It remains uncertain whether Type 1 diabetes (T1D) is linked to the risk of breast cancer (BC), with previous epidemiological findings yielding inconsistent conclusions. 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). 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. 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.
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BibTeX
@article{xie2026type,
title = {{Type 1 Diabetes and Breast Cancer Risk: Evidence From an Updated Meta-Analysis and Mendelian Randomization Study.}},
author = {Yi Xie and Qimou Lin and Jianhua Guan and Junda Li and Lin Yuan and Junhong Wen and Bo Xu},
journal = {International journal of endocrinology},
year = {2026},
month = nov,
doi = {10.1155/ije/2837214},
url = {https://europepmc.org/article/MED/42996517},
note = {CC BY},
}
RIS
TY - JOUR
TI - Type 1 Diabetes and Breast Cancer Risk: Evidence From an Updated Meta-Analysis and Mendelian Randomization Study.
AU - Yi Xie
AU - Qimou Lin
AU - Jianhua Guan
AU - Junda Li
AU - Lin Yuan
AU - Junhong Wen
AU - Bo Xu
PY - 2026
DA - 2026/11/05
JO - International journal of endocrinology
DO - 10.1155/ije/2837214
UR - https://europepmc.org/article/MED/42996517
AB - It remains uncertain whether Type 1 diabetes (T1D) is linked to the risk of breast cancer (BC), with previous epidemiological findings yielding inconsistent conclusions. 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). 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. 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.
SN - 1687-8337
SN - 1687-8345
ER -