Causality between telomere length and breast diseases: a two-sample bidirectional Mendelian randomization study.

Background: The relationship between telomere length and breast diseases remains unclear, with conflicting evidence for breast cancer. Using an innovative genetic approach, we were the first to comprehensively assess their bidirectional causal relationship.

Methods: Telomere length, breast cancer, benign neoplasm of breast, and breast inflammation were extracted from the genome-wide Association study (GWAS) database as the basis for large-scale population studies. The interaction of telomere length and breast diseases as exposure and outcome factors was analyzed by Mendelian randomization (MR).

Results: When telomere length was used as an exposure factor and breast diseases as an outcome, the P value of MR was less than 0.05. Breast cancer (odds ratio (OR) = 1.130, 95% confidence interval (CI) = 1.047-1.219, P = 0.0016), benign neoplasm of breast (OR = 1.002, 95%CI = 1.001-1.004, P = 0.0007) and breast inflammation (OR = 1.487, 95%CI = 1.008-2.191, P = 0.0453). When breast diseases were taken as an exposure factor and telomere length was taken as an outcome, the P value of MR between breast cancer, benign neoplasm of breast, and telomere length was greater than 0.05, and breast inflammation could not be calculated by MR.

Conclusion: Telomere length is a risk factor for breast diseases, and longer telomeres increase the risk of breast cancer, benign neoplasm of breast, and breast inflammation. However, the reverse study showed no causal association between breast cancer, benign neoplasm of breast and telomere length, and the causal association between breast inflammation and telomere length was not clear. Moreover, further studies are needed to validate our findings in non-European populations.