Relationship between the polymorphism of tumor necrosis factor-α-308 G>A and susceptibility to inflammatory bowel diseases and colorectal cancer: a meta-analysis

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-alpha-308 G > A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-alpha-308 G > A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-alpha-308 G > A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-alpha-308 G > A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-alpha and other cytokines, and the interaction with environmental factors, in future studies. European Journal of Human Genetics (2011) 19, 432-437; doi:10.1038/ejhg.2010.159; published online 19 January 2011