Genetically determined telomere length as a risk factor for hematological malignancies: evidence from Mendelian randomization analysis.

Background: Over the past years, the exact correlation between telomere length and hematological malignancies was still not fully understood.

Methods: We performed a two-sample Mendelian randomization study to investigate the causal relationship between telomere length and hematological malignancies. We selected genetic instruments associated with telomere length. The genetic associations for lymphoid and hematopoietic malignant neoplasms were obtained from the most recent publicly accessible FinnGen study R9 data. Inverse variant weighted (IVW) analysis was adopted as the primary method, and we also performed the weighted-median method and the MR-Egger, and MRPRESSO methods as sensitive analysis.

Results: Significant associations have been observed between telomere length and primary lymphoid (IVW: OR = 1.52, = 2.11 × 10), Hodgkin lymphoma (IVW: OR = 1.64, = 0.014), non-Hodgkin lymphoma (IVW: OR = 1.70, = 0.002), B-cell lymphoma (IVW: OR = 1.57, = 0.015), non-follicular lymphoma (IVW: OR = 1.58, = 1.7 × 10), mantle cell lymphoma (IVW: OR = 3.13, = 0.003), lymphoid leukemia (IVW: OR = 2.56, = 5.92E-09), acute lymphocytic leukemia (IVW: OR = 2.65, = 0.021) and chronic lymphocytic leukemia (IVW: OR = 2.80, = 8.21 × 10), along with multiple myeloma (IVW: OR = 1.85, = 0.016).

Conclusion: This MR study found a significant association between telomere length and a wide range of hematopoietic malignancies. But no substantial impact of lymphoma and hematopoietic malignancies on telomere length has been detected.