Association of four polymorphisms in the death receptor 4 gene with cancer risk: an updated meta-analysis

To date, no scientific consensus about the associations of DR4 C626G, A683C, A1322G, and G422A polymorphisms with cancer risk has been reached. Therefore, we conducted a meta-analysis to assess the associations. This meta-analysis involved 16 studies, of which 15 (4,261 cases and 4,598 controls) described C626G genotypes, 8 (2,898 cases and 3,135 controls) described A683C genotypes, 6 (1,564 cases and 1,673 controls) described A1322G genotypes, and 5 (584 cases and 607 controls) described A683C genotypes. We associated all the four polymorphisms with cancer risk. The C626G polymorphism was associated with slightly elevated cancer risk in recession model comparison [odds ratio (OR) = 1.12, 95 % confidence interval (CI) = 1.00-1.26, P (heterogeneity) = 0.425]. In the subgroup analysis by cancer type, significantly elevated cancer risks were found among groups with lung cancer for heterozygote comparison (OR = 1.76, 95 % CI = 1.00-3.09, P (heterogeneity) = 0.863). The A1322G polymorphism was associated with significantly elevated cancer risk in the different models (heterozygote comparison: OR = 1.21, 95 % CI = 1.00-1.46, P (heterogeneity) = 0.347; dominant model: OR = 1.21, 95 % CI = 1.01-1.46, P (heterogeneity) = 0.189; allele model comparison for G allele vs. A allele: OR = 1.17, 95 % CI = 1.02-1.35, P (heterogeneity) = 0.173). The A683C and G422A polymorphisms were not associated with cancer risk in all genetic models. The C626G and A1322G polymorphisms are associated with increased cancer risk, but the A683C polymorphism is rarely associated with cancer risk.