Causal relationship between branched-chain amino acids and leukemia risk: insights from a two-sample Mendelian randomization study.

Autor: Chen S; School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, People's Republic of China., He G; School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, People's Republic of China., Zhang M; School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, People's Republic of China., Tang N; Hematology Department, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People's Republic of China., Zeng Y; Hematology Department, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People's Republic of China.
Jazyk: angličtina
Zdroj: Hematology (Amsterdam, Netherlands) [Hematology] 2024 Dec; Vol. 29 (1), pp. 2433904. Date of Electronic Publication: 2024 Dec 11.
DOI: 10.1080/16078454.2024.2433904
Abstrakt: Background: Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids involved in protein synthesis, energy metabolism, and immune regulation. While BCAAs are known to influence cancer biology, their role in leukemia remains unclear. This study employs Mendelian randomization (MR) analysis to explore the causal relationship between BCAA levels and four leukemia subtypes: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).
Methods: Data from genome-wide association studies (GWAS) were used to select single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for BCAA levels. The inverse-variance weighted (IVW) method served as the primary analytical approach, with heterogeneity assessed via Cochran's Q test and pleiotropy through MR-Egger intercept. Sensitivity analysis was performed using leave-one-out analysis.
Results: A significant inverse association was observed between total BCAA levels, leucine, valine, and ALL risk. Total BCAA levels showed an odds ratio (OR) of 0.16 (95% CI: 0.05-0.54, p=0.003), leucine 0.17 (95% CI: 0.04-0.61, p=0.007), and valine 0.21 (95% CI: 0.07-0.61, p=0.004). No significant associations were found for AML, CLL, or CML.
Conclusion: This study suggests that BCAAs, particularly leucine and valine, may protect against ALL, offering insights into leukemia metabolic regulation and potential targets for prevention and therapy.
Databáze: MEDLINE
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