{"title":"Causal relationship between branched-chain amino acids and leukemia risk: insights from a two-sample Mendelian randomization study.","authors":"Shupeng Chen, Guilian He, Meiling Zhang, Nana Tang, Yingjian Zeng","doi":"10.1080/16078454.2024.2433904","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2433904"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/16078454.2024.2433904","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.