Causality between Telomere Length and the Risk of Hematologic Malignancies: A Bidirectional Mendelian Randomization Study.

Abstract

Growing evidence indicates a relationship between telomere length (TL) and the stage, prognosis, and treatment responsiveness of hematopoietic malignancies. However, the relationship between TL and the risk of hematologic malignancies remains unclear, considering the vulnerability of observational studies to potential confounding and reverse causation. A two-sample bidirectional Mendelian randomization (MR) analysis was conducted utilizing publicly available genome-wide association study data to assess whether TL was causally associated with the risk of hematologic malignancies. The inverse variance weighted approach was used as the primary assessment approach to evaluate the effects of the causes, augmented by the weighted median and MR-Egger methods. Cochran's Q test, MR-Egger intercept test, MR-Pleiotropy Residual Sum and Outlier test, and leave-one-out analysis were performed to evaluate sensitivity, heterogeneity, and pleiotropy. According to forward MR estimations, longer TL was related to an increased risk of acute lymphocytic leukemia (OR = 2.690; P = 0.041), chronic lymphocytic leukemia (OR = 2.155; P = 0.005), multiple myeloma (OR = 1.845; P = 0.024), Hodgkin lymphoma (OR = 1.697; P = 0.014), and non-Hodgkin lymphoma (OR = 1.737; P = 0.009). Specific types of non-Hodgkin lymphoma were also associated with TL. The reverse MR results revealed that hematologic malignancies had no effect on TL. This MR analysis revealed an association between longer TL and an increased risk of specific hematologic malignancies, indicating a potential role of TL in risk evaluation and management in hematologic malignancies.

Significance: In contrast to observational studies, this study uncovered the reliable causal relationships between TL and hematologic malignancies, emphasizing the potential role of telomeres in tumor development. TL maintenance may offer a promising strategy to reduce the risk of hematologic malignancies.