207P - Associations of diabetic background retinopathy and ER+ breast cancer risk: A Mendelian randomization study

Background

Diabetes mellitus is considered as a potential risk factor for breast cancer, yet the relationship between diabetic background retinopathy (DBR) and breast cancer remains uncertain. This study leverages mendelian randomization (MR) to explore the genetic link between diabetic background retinopathy (DBR) and estrogen receptor-positive (ER+) breast cancer, highlighting the connection with diabetes-related conditions.

Methods

We acquired summary data from a genome-wide association study (GWAS) concerning DBR in the European population, with a focus on their relationship with ER+ breast cancer. We performed two-sample MR analysis with multiple approaches to evaluate the potential causal associations between DBR and ER+ breast cancer. Pleiotropy and Cochran's Q tests were utilized to determine horizontal pleiotropy and heterogeneity.

Results

Of the 205,044 participants (2,026 DBR cases) from FinnGenn, we identified 8 single nucleotide polymorphisms (SNPs) associated with the risk of ER+ breast cancer (69,501 ER+ breast cancer cases from iCOGS). The MR analysis showed a suggestive association between DBR susceptibility and ER+ breast cancer (weight median odds ratio [OR]: 0.971, 95% confidence interval [CI]: 0.955-0.987, P = 0.0006; simple mode OR: 0.964, P = 0.043; weight mode OR: 0.971, P = 0.015). The effect size estimate (β) for weight median model was -0.0294, indicating a 2.94% decrease in the odds of ER+ breast cancer per unit increase in genetically predicted DBR. Sensitivity analyses are consistent with the results, manifesting that our findings were convincing and robust.

Conclusions

These finding suggests that a potential inverse relationship between DBR and the risk of ER+ breast cancer. These findings could significantly impact screening and prevention strategies for diabetic populations, emphasizing the need for further research into this association.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.