A Trial Sequential Meta-analysis of TNF- α -308G>A (rs800629) Gene Polymorphism and Susceptibility to Colorectal Cancer

Abstract

Purpose: Tumor necrosis factor-alpha (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF -α -308 G>A (rs1800629) single nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF -α -308 G>A gene polymorphism with CRC risk.

Methods: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association.

Results: The pooled analysis indicated no risk associated with TNF -α -308 G>A SNP and overall CRC risk in five genetic comparison models, i.e., allelic (A vs. G: p=0.524; OR=1.074, 95% CI=0.863 to 1.335), homozygous (AA vs. GG: p=0.489; OR=1.227, 95% CI=0.688 to 2.188), heterozygous (AG vs. GG: p=0.811; OR=1.024, 95% CI=0.843 to 1.244), dominant (AA+AG vs. GG: p=0.630; OR=1.055, 95% CI=0.849 to 1.311) and recessive (AA vs. AG+GG: p=0.549; OR=1.181, 95% CI=0.686 to 2.033). Subgroup analysis revealed that TNF -α -308 G>A SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias.

Conclusions: No association of TNF -α -308 G>A SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF- α -308 G>A SNP in the etiology of CRC and to endorse the present findings.