A trial sequential meta-analysis of α -308G>A (rs800629) gene polymorphism and susceptibility to colorectal cancer.

Purpose: Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of -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 -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 -α 308 G>A SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: = 0.524; OR = 1.074, 95% CI = 0.863-1.335), homozygous (AA vs. GG: = 0.489; OR = 1.227, 95% CI = 0.688-2.188), heterozygous (AG vs. GG: = 0.811; OR = 1.024, 95% CI = 0.843-1.244), dominant (AA+AG vs. GG: = 0.630; OR = 1.055, 95% CI = 0.849-1.311) and recessive (AA vs. AG+GG: = 0.549; OR = 1.181, 95% CI = 0.686-2.033). Subgroup analysis revealed that -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 -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 α 308 G>A SNP in the etiology of CRC and to endorse the present findings.