Research Paper Volume 16, Issue 5 pp 4684—4698
Genetically determined telomere length as a risk factor for hematological malignancies: evidence from Mendelian randomization analysis
- 1 Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- 2 Department of Breast Center, West China Hospital, Sichuan University, Chengdu, China
Received: October 10, 2023 Accepted: January 29, 2024 Published: March 6, 2024
https://doi.org/10.18632/aging.205625How to Cite
Copyright: © 2024 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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, P = 2.11 × 10−6), Hodgkin lymphoma (IVW: OR = 1.64, P = 0.014), non-Hodgkin lymphoma (IVW: OR = 1.70, P = 0.002), B-cell lymphoma (IVW: OR = 1.57, P = 0.015), non-follicular lymphoma (IVW: OR = 1.58, P = 1.7 × 10−3), mantle cell lymphoma (IVW: OR = 3.13, P = 0.003), lymphoid leukemia (IVW: OR = 2.56, P = 5.92E-09), acute lymphocytic leukemia (IVW: OR = 2.65, P = 0.021) and chronic lymphocytic leukemia (IVW: OR = 2.80, P = 8.21 × 10−6), along with multiple myeloma (IVW: OR = 1.85, P = 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.
Abbreviations
HL: Hodgkin lymphoma; NHL: Non-Hodgkin lymphoma; DLBCL: Diffuse large B-cell lymphoma; NFL: Non-follicular lymphoma; MCL: Mantle cell lymphoma; FL: Follicular lymphoma; MZBL: Marginal zone B-cell lymphoma; ALL: Acute lymphocytic leukaemia; CLL: Chronic lymphocytic leukaemia; MM: Multiple myeloma; GWAS: Genome-wide association studies; IVW: Inverse-variance weighted; SNPs: Single nucleotide polymorphisms; IVs: Instrumental variables; WM: Weighted median; FDR: False discovery rate; OR: Odds ratio; CI: Confidence interval.