No association between three polymorphisms (rs1800629, rs361525 and rs1799724) in the tumor necrosis factor-α gene and susceptibility to prostate cancer: a comprehensive meta-analysis

Abstract

Background: Inflammation is one of the factors associated with prostate cancer. The cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in inflammation. Several studies have focused on the association between TNF-α polymorphisms and prostate cancer development. Our meta-analysis aimed to estimate the association between TNF-α rs1800629 (- 308 G/A), rs361525 (- 238 G/A) and rs1799724 polymorphisms and prostate cancer risk.

Methods: Eligible studies were identified from electronic databases (PubMed, Embase, Wanfang and CNKI) using keywords: TNF-α, polymorphism, prostate cancer, until Nov 15, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to determine the association from a quantitative point-of-view. Publication bias and sensitivity analysis were also applied to evaluate the power of current study. All statistical analyses were done with Stata 11.0 software.

Results: Twenty-two different articles were included (22 studies about rs1800629; 8 studies for rs361525 and 5 studies related to rs1799724). Overall, no significant association was found between rs1800629 and rs1799724 polymorphisms and the risk of prostate cancer in the whole (such as: OR = 1.03, 95% CI = 0.92-1.16, P = 0.580 in the allele for rs1800629; OR = 0.95, 95% CI = 0.84-1.07, P = 0.381 in the allele for rs1799724). The rs361525 polymorphism also had no association with prostate cancer in the cases (OR = 0.93, 95% CI = 0.66-1.32, P = 0.684 in the allele) and ethnicity subgroup. The stratified subgroup of genotype method, however, revealed that the rs361525 variant significantly decreased the risk of prostate cancer in the Others (OR = 0.65, 95% CI = 0.47-0.89, P = 0.008, A-allele vs G-allele) and PCR-RFLP (OR = 2.68, 95% CI = 1.00-7.20, P = 0.050, AG vs GG or AA+AG vs GG) methods.

Conclusions: In summary, the findings of the current meta-analysis indicate that the TNF-α rs1800629, rs361525 and rs1799724 polymorphisms are not correlated with prostate cancer development, although there were some pooled positive results. Further well-designed studies are necessary to form more precise conclusions.

Keywords: Meta-analysis; Polymorphism; Prostate cancer; Susceptibility; Tumor necrosis factor-alpha.

Fig. 1

A flowchart illustrating the search strategy about TNF-α rs1800629, rs361525, rs1799724 and rs1799964 polymorphisms and PCA risk was shown

Fig. 2

MAF for the TNF-α rs1800629, rs361525 and rs1799724 polymorphsms from 1000 Genomes Browser. Vertical line, MAF; Horizontal line, ethnicity type. EAS: East Asian; EUR: European; AFR: African; AMR: American; SAS: South Asian

Fig. 3

Meta-analysis. a. Forest plots of TNF-α rs1800629 polymorphism and PCA risk (A-allele vs. G-allele). b. Forest plot of TNF-α rs1799724 polymorphism and PCA risk (T-allele vs. C-allele). c. Forest plot of TNF-α rs361525 polymorphism and PCA risk (AA vs. GG). d. Forest plot of TNF-α rs361525 polymorphism and PCA risk (A-allele vs. G-allele) on subgroup of genotyping method (Others). e. Forest plot of TNF-α rs361525 polymorphism and PCA risk (A-allele vs. G-allele) on subgroup of genotyping method (PCR-RFLP)

Fig. 4

Publication bias. a. Begg’s funnel plot for publication bias test (A-allele vs. G-allele). b. Egger’s publication bias plot (A-allele vs. G-allele). c. Begg’s funnel plot for publication bias test (A-allele vs. G-allele). d. Egger’s publication bias plot (A-allele vs. G-allele)

Fig. 5

Sensitivity analysis. a. Sensitivity analysis for TNF-α rs1800629 polymorphism and RA risk (A-allele vs. G-allele). b. Sensitivity analysis between TNF-α rs361525 polymorphism and RA risk (A-allele vs. G-allele)