Association between TLR 2 (rs3804099), TLR4 (rs4986790), and TLR 9 (rs187084) polymorphism and leukemia risk: a systematic review and meta-analysis

Toll-like receptors (TLRs) are crucial components of innate immunity. A specific form of genetic variation in TLR genes may increase the chance of developing leukemia. The present investigation conducted a comprehensive meta-analysis to examine the correlation between three TLR polymorphisms, namely TLR2 (rs3804099), TLR4 (rs4986790), and TLR9 (rs187084), within the leukemia risk group. An in-depth literature search was performed using Web of Science, PubMed, and Google Scholar to identify noteworthy research published in these scientific databases from 2012 to 2024. Research articles were evaluated according to rigorous inclusion criteria, and data was compiled for meta-analysis using Microsoft Excel (Ver. 2013), MedCalc (Ver. 19.3), and RevMan software (Ver. 5.3). Finally, 11 qualified studies were selected for the ongoing investigation, encompassing a combined total of 1315 leukemia cases and 1340 controls. Using a dominant genotype model, the meta-analysis found that the TLR2 (rs3804099) and TLR9 (rs187084) polymorphisms were strongly linked to higher risk of leukemia, with ORs of 2.042 (95% CI: 1.35-3.08, p = 0.001) and 1.38 (95% CI: 1.14-1.67, p = 0.001) respectively. Notably, the TLR4 (rs4986790) polymorphism did not exhibited any substantial correlation with the incidence of leukemia. The results indicate that variations in TLR2 and TLR9 genes could be considered a novel genetic biomarker for the leukemia development, highlighting their potential use in risk assessment and targeted therapies. This emphasizes the possibility of using these variations in evaluating risk and developing targeted remedies. However, greater research capacities are required to research into the fundamental mechanisms and authenticate these trends in other populations.