Association Of-308G/A,-238G/A TNF-α Polymorphisms with Multiple Myeloma Risk and Survival: A Systematic Review and Meta-Analysis

Tumor necrosis factor alpha (TNF-alpha) plays a key role in multiple diseases, including cancer. Eighteen studies were included in this systematic review and meta-analysis examining TNF-alpha polymorphisms in association with risk, and five studies in survival of multiple myeloma (MM). No association was found between -308G/A and -238G/A TNF-alpha polymorphisms and MM susceptibility or survival. Introduction: Tumor necrosis factor alpha (TNF-alpha) is a cytokine with a key role in proinflammation and multiple diseases, including cancer. The gene encoding TNF-alpha is located within a highly polymorphic region on chromosome 6p21.3; two polymorphisms -308G/A (rs1800629) and -238G/A (rs361525) have been associated with occurrence of human diseases. There is a debate in recent meta-analyses that reached discrepant conclusions regarding the potential role of TNF-alpha polymorphisms in multiple myeloma (MM) risk. The aim of this systematic review and meta-analysis is to investigate the association between the aforementioned two polymorphisms with the risk and survival of MM. Materials and methods: Eligible articles were identified through an extensive search in PubMed database (end of search: June 18, 2020). The pooled effect estimates were calculated following the random-effects models by Der Simonian and Laird. Separate analyses were conducted by ethnicity. Between-study heterogeneity was quantified, and the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was evaluated. Results: Eighteen studies (2934 cases, 4291 controls) have been included in the quantitative synthesis examining risk and 5 studies for survival (557 cases). No association was found between -308G/A and -238G/A TNF-alpha polymorphisms and MM susceptibility in all genetic models for both Caucasian and East Asian populations. There was no association between -308G/A and -238G/A TNF-alpha polymorphisms and survival (overall or progression-free) of MM. Conclusion: This systematic review and meta-analysis did not reveal a significant effect of -308G/A and -238G/A TNF-alpha polymorphisms upon risk or survival of MM. (C) 2021 Elsevier Inc. All rights reserved.