Abstract
Objective:Tumor necrosis factor alpha (TNF-α) is an important cytokine involved in inflammation, immune response, and other biological processes. The association between polymorphism -308G/A in its promoter and the risk of multiple myeloma (MM) is not clear. Thus, we conducted a meta-analysis to clarify this question.Materials and Methods:Twelve eligible studies, which included 2204 MM cases and 3478 controls, were enrolled in our meta-analysis by searching the PubMed, China National Knowledge Infrastructure, Scopus, Web of Science, and Google Scholar databases up to December 2018. The effect of polymorphism -308G/A on MM risk was evaluated by calculating the pooled odds ratio (OR) and the 95% confidence interval (CI). Furthermore, the Q-test and I2 statistical analyses were used to estimate the degree of heterogeneity. Sensitivity analysis was conducted to test the robustness of the meta-analysis results. Publication bias was assessed by Egger’s test and visual inspection of a funnel plot.Results:In the dominant model, -308G/A polymorphism was associated with reduced MM risk (OR=0.80, 95% CI: 0.65-0.97), and it also demonstrated a significant protective effect with a pooled OR of 0.82 (95% CI: 0.68-0.99) in the Caucasian subgroup. Because of the limited number of individual studies with AA genotype carriers, only eight studies were included in the recessive model, and no significant difference was observed. Moreover, the meta-analysis of the allele frequency demonstrated that the A allele has a protective effect against MM risk with a pooled OR of 0.83 (95% CI: 0.69-0.99). Sensitivity analysis suggested that the synthesized effect size was not influenced by any individual study. Moreover, the Egger’s test statistical analysis suggested that publication bias was not obvious in the present analysis.Conclusion:Overall, the -308G/A polymorphism was associated with reduced MM risk in the dominant model and allele frequency. Further investigation is needed to gain better insight.
Highlights
Multiple myeloma (MM) is a bone marrow-based disseminated neoplasm commonly preceded by premalignant monoclonal gammopathy of undetermined significance [1]
In the dominant model, -308G/A polymorphism was associated with reduced MM risk (OR=0.80, 95% confidence interval (CI): 0.65-0.97), and it demonstrated a significant protective effect with a pooled odds ratio (OR) of 0.82 in the Caucasian subgroup
The meta-analysis of the allele frequency demonstrated that the A allele has a protective effect against MM risk with a pooled OR of 0.83
Summary
Multiple myeloma (MM) is a bone marrow-based disseminated neoplasm commonly preceded by premalignant monoclonal gammopathy of undetermined significance [1]. Among the hematologic malignancy types, MM accounts for approximately 10% of diagnosed cases, maintaining the second position after non-Hodgkin’s lymphoma [2]. According to the latest statistics, there are 30,330 new MM cases and 12,650 deaths attributed to MM in the United States annually [3]. With the rapid progress made in pharmaceutical research, novel proteasome inhibitors and immune modulatory drugs have been applied in the treatment of MM [4], and the prognosis of MM has significantly improved among all MM patients. Despite the improvement in both treatment and survival, MM is currently regarded as an incurable disease, and the major goal of treatment is to achieve partial or complete remission. It is of critical importance to investigate the risk factors of MM and to identify high-risk populations at the early stage of the disease
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